Design, synthesis, characterization of some new 1,2,3-triazolyl chalcone derivatives as potential anti-microbial, anti-oxidant and anti-cancer agents via a Claisen-Schmidt reaction approach

Article abstract of DOI:10.1039/c6ra22705h

The synthesis of a new series of (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-aryl prop-2-en-1-one (5a-k) and (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(1,3-diaryl-1H-pyrazol-4-yl)prop-2-en-1-one (6a-e) were carried out via a Claisen-Schmidt condensation of 1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}ethanone (4) with different aryl and 1,3-diaryl-1H-pyrazole-4-carbaldehydes iii(a-e) in the presence of ethanol and aqueous sodium hydroxide mixture respectively. The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectral data and elemental analysis. Further, they were screened for their in vitro anti-microbial, anti-oxidant and anti-cancer activities. Most of the synthesized compounds were displayed broad spectrum of anti-microbial, anti-oxidant activities and some of them exhibits moderate to excellent anti-cancer activities on breast cancer cell lines. Overall, this work has contributed to the development of promising leads for anti-microbial, anti-oxidant and anti-cancer activities.

Full text of DOI:10.1039/c6ra22705h

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Page 1 of 23
RSC Advances
Design, synthesis, characterization of some new 1,2,3-Triazolyl chalcone derivatives as potential anti-microbial, anti-
oxidant and anti-cancer agents via a Claisen-Schmidt reaction approach
Manjunatha Bhata,b, Nagaraja G.K.a,*, Divyaraj Pa,b, Harikrishna Nb, Sreedhara Ranganath Pai Kc, Subhankar Biswasc, Peethamber
S.K.d
aDepartment of Studies in Chemistry, Mangalore University, Mangalagangothriꢀ574199, Karnataka, India
bSeQuent Scientific Limited, No:120 A&B, Industrial Area, Baikampady, New Mangalore, Karnatakaꢀ575 011, India.
cDepartment of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal, Karnatakaꢀ576104, India.
dDepartment of Biochemistry, Jnanasahyadri, Kuvempu University, Shankarghatta, Karnatakaꢀ577 451, India.
Abstract
Synthesis of new series of (2E)ꢀ1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ꢀ3ꢀaryl propꢀ2ꢀenꢀ1ꢀone
(5a-k) and (2E)ꢀ1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ꢀ3ꢀ(1,3ꢀdiarylꢀ1Hꢀpyrazolꢀ4ꢀyl)propꢀ2ꢀ
enꢀ1ꢀone (6a-e) were carried out via a ClaisenꢀSchmidt condensation of 1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ
1,2,3ꢀtriazolꢀ4ꢀyl}ethanone (4) with different aryl and 1,3ꢀdiarylꢀ1Hꢀpyrazoleꢀ4ꢀcarbaldehydes iii(a-e) in presence of ethanol and aqueous
1
13
sodium hydroxide mixture respectively. The newly synthesized compounds were characterized by IR, H NMR, C NMR, mass spectral data
View Article Online
and elemental analysis. Further, they were screened for their inꢀvitro antiꢀmicrobial, antiꢀoxidant and antiꢀcancer activities. Most of the
DOI: 10.1039/C6RA22705H
synthesized compounds were displayed broad spectrum of antiꢀmicrobial, antꢀoxidant activities and some of them exhibits moderate to excellent
antiꢀcancer activities on breast cancer cell lines. Overall, this work has contributed to the development of promising leads for antiꢀmicrobial,
antiꢀoxidant and antiꢀcancer activities.
Key words: 1,2,3ꢀTriazole, ClaisenꢀSchmidt condensation, antiꢀmicrobial activity, antiꢀoxidant activity, antiꢀcancer activity.
*Corresponding author. Tel.: +91ꢀ824ꢀ2287262(O)
Eꢀmail address: nagarajagk@gmail.com
1. Introduction
During the past few decades, there has been an severe increase in the population suffering with infectious disease due to multiꢀdrug resistance,
which often resulting from the overꢀexpression of multiꢀdrug efflux systems and their wide spread usage.1 Microbial infections are the most
prominent death causing disease after heart attack in the world, because of their ability to spread rapidly, combined with their toxicity and
resistance towards existing antiꢀbiotic drugs.2,3 These trends have emphasized the urgent need and challenge for the development of more
effective, potent and broad spectrum antimicrobial novel drugs with good bioavailability, no or fewer side effects to cure microbial infections.4
In this context, the drug discovery has acquired a considerable interest in microbial target based synthesis of novel antimicrobial agents.
On the other hand, Cancer remains to be the leading cause of death in humans second only to cardiovascular diseases and more than 70% of all
cancer deaths occur in developing and underꢀdeveloped countries.5,6 Cancers have been reported as one of the Global Burden of Diseases (World
Health Organization, 2008) and are estimated to be one of main causes of death in the coming decades.7,8 Breast cancer is one of the most
commonly diagnosed cancers, accounting for ~20% of all malignancies worldwide and over half a million women develop breast cancer every
year. In India, almost 100,000 women are diagnosed with breast cancer every year and a rise to 131,000 cases is predicted by 2020.9,10 Many
current breast cancer chemotherapy treatments are often associated with side effects and the development of drug resistance in cancer cells,
whereby majority of the patients succumb to their disease within 2 years of diagnosis. Hence, the design and development of new drugs for
different types of breast cancer therapeutics remains to be an important and challenging task for medicinal chemist’s worldwide.11ꢀ13
Similarly, numerous studies have demonstrated that in addition to cancer, antiꢀoxidants plays an important role in the body defense mechanism
by regulating the generation and elimination of reactive oxygen species (ROS) like hydroxyl radicals, superoxide radicals etc. which are
generated from excessive oxidative stress and normal metabolic activities. The oxidative stress reflects an imbalance between the oxidants and
the antioxidant favoring the oxidants implies damage of all essential bioꢀcompounds like proteins, DNA and membrane lipids and can result in
cell death.14 There is increasing evidence showing the involvement of oxidative stress induced by free radicals and reactive oxygen species
(ROS) in a variety of diseases and pathophysiological events including inflammation, cancer, myocardial infraction, arthritis and
neurodegenerative disorders.15 Antioxidants can minimize or inhibit the oxidative damage by interrupting the free radical formation or
terminating the chain reaction. Antioxidants may slow or possibly prevent the development of the above mentioned diseases.16,17 On the other
hand, many chemotherapeutic agents act by producing free radicals, causing oxidative stress in normal cells.18 A mono therapy of an anticancer
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drug with antioxidant properties will probably become more advantageous from the pharmacoꢀeconomic point of view. Thus, the discovery and
development of novel antiꢀoxidants attained great importance in organic chemistry.
In recent years, heterocyclic compounds containing nitrogen plays important role in agrochemical and pharmaceuticals. In the family of
Nitrogen heterocycles, triazoles and their derivatives occupy a central position due to their biologically active nature.19 Moreover, 1,2,3ꢀ
Triazoles derivatives present in various medicinal agents were capable of forming hydrogen bonds which in turn improves their solubility and
ability to interact with bimolecular targets.20 Most of the literature studies revealed that, 1,2,3ꢀtriazoles are the key moieties in heterocyclic
chemistry and have been used for broad therapeutic applications due to their diverse biological activities.21 They are known to possess a wide
range of pharmacological activities like antiꢀmicrobial,22,23 antiꢀconvulsant,24 antiꢀtubercular,25 antiꢀdiabetic,26 antiꢀmalarial,27 antiꢀoxidant,25 and
antiꢀcancer activities.28,29 Similarly, Chalcones and their derivatives are abundant in edible plants where they are considered to be the precursors
of flavonoids or isoflavonoids30 and constitute an important group of natural and synthetic products with wide range of pharmacological
activities as its derivatives found to exhibit variety of biological and pharmacological activities, including effects as antimicrobial,31,32 antiꢀ
inflammatory,33 antiꢀoxidant,34 antiꢀmalarial,35 anticonvulsant,36 anticancer,37,38 etc. Figure 1
Figure 1
In view of the above mentioned findings and inꢀcontinuation of our interest in exploration of novel heterocyclic scaffolds for antiꢀmicrobial,
antiꢀoxidant and antiꢀcancer activities we hereby report the synthesis of some novel 1,2,3ꢀtriazolylꢀchalcones as key nucleus and evaluate their
antiꢀmicrobial, antiꢀoxidant and antiꢀcancer potential with the hope of improving its biological activities. Most of the compounds exhibits good
biological activities. The synthetic strategy and representative examples of 1,2,3ꢀtriazoleꢀchalcones via a molecular hybridization technique was
View Article Online
represented in Figure 2.
DOI: 10.1039/C6RA22705H
Figure 2
2. Results and discussion
2.1. Chemistry
The synthetic protocol for the title compounds, (2E)ꢀ1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ꢀ3ꢀ
aryl propꢀ2ꢀenꢀ1ꢀone (5a-k) and (2E)ꢀ1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ꢀ3ꢀ(1,3ꢀdiarylꢀ1Hꢀ
pyrazolꢀ4ꢀyl)propꢀ2ꢀenꢀ1ꢀone (6a-e) was outlined in Scheme 1, and were synthesized by the ClaisenꢀSchmidt condensation of 1ꢀ{1ꢀ[2,3ꢀ
dichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ethanone (4) with different aryl and 1,3ꢀdiarylꢀ1Hꢀpyrazoleꢀ4ꢀ
carbaldehydes iii(a-e) in presence of ethanol and aqueous sodium hydroxide mixture respectively with good yields (70ꢀ80%). The key starting
material 1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ethanone (4) were synthesized by 1,3ꢀdipolar
cyclo addition reaction between 3ꢀazidoꢀ1,2ꢀdichloroꢀ4ꢀmethylꢀ5ꢀ(trifluoromethyl) benzene (3) and Acetyl acetone in presence of Sodium
methoxide in methanol. The intermediate 3ꢀazidoꢀ1,2ꢀdichloroꢀ4ꢀmethylꢀ5ꢀ(trifluoromethyl) benzene (3) were synthesized from 1,2ꢀdichloroꢀ4ꢀ
methylꢀ3ꢀnitroꢀ5ꢀ(trifluoromethyl) benzene (1) following literature procedures.39
Scheme 1
Structures of all the synthesized compounds (5a-n) and (6a-e) were established on the basis of their spectral (IR, NMR and Mass) and
elemental (C, H and N) analysis. Analytical and spectral data of all the synthesized compounds were in full agreement with the proposed
structures and also discussed for a representative compound 5g: The IR spectrum of (5g) showed absorption peak at 2936 cmꢀ1 assigned to
aromatic CꢀH stretch. The peak for C=N was observed at 1573 cmꢀ1. The peak at 1593 and 1256 cmꢀ1 were assigned to C=O and CꢀO stretch
respectively. The medium absorption at 1177 and 824 cmꢀ1 was due to the presence of CꢀF and CꢀCl bonds respectively. The 1H NMR spectrum
of (5g) showed three singlet’s at δ (ppm) 2.09, 2.50 and 3.87 were assigned to methyl protons of 1,2,3ꢀtriazole ring, 2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ
(trifluoromethyl) phenyl and 4ꢀmethoxy phenyl respectively. The two distinct doublet signals at δ 6.94 and 7.69 (J = 8.6 Hz) integrating to four
protons were assigned to aromatic protons of 4ꢀmethoxy phenyl ring. The singlet signal at δ 8.00 were assigned to aromatic protons of 2,3ꢀ
dichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl) phenyl moiety. Similarly two doublets at δ 7.92 and 7.98 (J = 15.8 Hz) integrating for two protons were
assigned to two olefin (CH=CH) protons. The signals due to carbonyl methyl protons at δ 2.77 were disappeared indicating the formation of the
compound (5c). The 13C NMR spectrum of (5g) showed signals at δ (ppm) 9.23, 14.29, 55.42 and 184.00 corresponds to three methyl carbons of
1,2,3ꢀtriazole, 2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl) phenyl, 4ꢀmethoxy phenyl ring and carbonyl carbon attached to triazole ring
respectively along with other characteristic signals. Similarly for compound (6e), the IR spectrum showed absorption peak at 3066 cmꢀ1 assigned
to aromatic CꢀH stretch. The peak for C=N was observed at 1567 cmꢀ1. The peak at 1668 and 1260 cmꢀ1 were assigned to C=O and CꢀO stretch
1
respectively. The medium absorption at 1177, 1035 and 824 cmꢀ1 was due to the presence of CꢀF, CꢀBr and CꢀCl bonds respectively. The H
NMR spectrum of (6e) showed two singlet’s at δ (ppm) 2.09 and 2.49 were assigned to methyl protons of 1,2,3ꢀtriazole ring and 2,3ꢀdichloroꢀ6ꢀ
methylꢀ5ꢀ(trifluoromethyl) phenyl respectively. The distinct triplet signal at δ 7.34 (J = 7.6 Hz) integrating to two protons were assigned to
aromatic protons of phenyl and 3ꢀbromo phenyl ring respectively. The three singlet signals at δ 7.94, 7.99 and 8.53 were assigned to aromatic
protons of 3ꢀbromo phenyl, 2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl) phenyl and pyrazole moiety respectively. Similarly three doublets at δ
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RSC Advances
7.51, 7.73 and 7.81 (J = 8.0 Hz) integrating for six protons were assigned to aromatic protons of phenyl and 3ꢀbromo phenyl ring respectively.
Similarly two doublets at δ 8.0 and 8.02 (J = 17.0 Hz) integrating for two protons were assigned to two olefin (CH=CH) protons. The signals due
13
to carbonyl methyl protons at δ 2.77 were disappeared indicating the formation of the compound (6e). The C NMR spectrum of (6e) showed
signals at δ (ppm) 9.29, 14.24 and 184.10 corresponds to two methyl carbons of 1,2,3ꢀtriazole and 2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)
1
13
phenyl ring and carbonyl carbon attached to triazole ring respectively along with other characteristic signals. The IR, H NMR and C NMR
spectra of other compounds (5a-k) and (6a-e) has shown similar characteristic properties. The physicochemical data of the compounds (5a-k)
and (6a-e) were presented in Table 1.
Table 1
2.2. Biological studies
2.2.1. In-vitro anti-microbial activity
The antiꢀmicrobial activities of the newly synthesized compounds (5a-k) and (6a-e) were tested against four different bacteria and three different
funguses. Two gramꢀpositive strains Staphylococcus aureus (MTCC 1430) and Bacillus subtilis (MTCC 441). Two gramꢀnegative strains were
Escherichia coli (MTCC 1573) and Pseudomonas aeruginosa (MTCC 424). All bacterial strains were maintained on nutrient agar medium at
37˚C. Fungi: Aspergillus flavus, Chrysosporium keratinophilum and Candida albicans (MTCC 227) was used in this study. All fungi strains
were maintained on potato dextrose agar (PDA) at 25 ˚C.
The synthesized compounds was first dissolved in DMSO to a different concentration (1 and 0.5 mg/ml), and then sterilized by filtration
View Article Online
through 0.22 µm Millipore filters. The antibacterial activity of newly synthesized compounds (5a-k) and (6a-e) was determined by well plate
DOI: 10.1039/C6RA22705H
method in nutrient agar media.40 The compounds were tested against a panel of pathogenic microorganisms, including Escherichia coli (MTCC
1573), Bacillus subtilis (MTCC 441) , Staphylococcus aureus (MTCC 1430) and Pseudomonas aeruginosa (MTCC 424). Microorganism strains
were maintained on nutrient agar medium at 37˚C. The cultures were inoculated in fresh 10 ml nutrient broth to yield an initial suspension of
approximately 10ꢀ100 c.f.u/ml. All broths were then incubated statically at the aforementioned temperatures for microorganisms, for 18ꢀ24 h so
that all cells were in the stationary phase. Susceptibility of the test organism to the compounds was determined by employing in the well plate
technique. The bacterial suspensions were diluted tenfold in sterilized distilled water, and 0.1 ml from the appropriate dilution was spread plated
on nutrient agar in order to give a population approximately 106 cfu/plate. Six millimeter diameter well were then punched carefully using a
sterile cork borer and 30 µL of test solutions of different concentrations were added into each labeled well. The same procedure was repeated for
different microꢀorganisms. Each experiment was carried out in triplicate. After the incubation, the inhibition zone was measured and the values
for DMSO were subtracted to get the actual values. Ciproflaxin was used as standard drug. MIC (Minimum Inhibitory Concentration) was
determined according to the broth micro dilution method described, with suitable modifications.41 The test compounds were first (1.5 mg/ml)
dissolved in DMSO and then sterilized by 0.5 µm filtration. The final concentration of DMSO in each medium was maintained 1%, so that it
does not affect the growth of the test strain. Broth micro dilution methods were used as previously described with slight modifications.41 Briefly,
logarithmic serial twoꢀfold dilutions (serial dilution method) of the test compounds and controls were prepared in DMSO, and 30 µL of each
dilution was added to 3 mL of Nutrient broth. Thirty microliters of the exponentially growing bacterial cells of Escherichia coli (MTCC 1573),
Bacillus subtilis (MTCC 441), Staphylococcus aureus (MTCC 1430) and Pseudomonas aeruginosa (MTCC 424) (final 5.0 × 105 c.f.u/mL) were
inoculated into the broth. After the cultures were incubated at 37°C for 24 h, the MIC (Minimum Inhibitory Concentration) value, representing
the lowest concentration (highest dilution) that completely inhibited the formation of visible growth, was evaluated after 24 h of incubation at
37°C. The experiments were performed in triplicates.
Antifungal studies of newly synthesized compounds (5a-k) and (6a-e) were determined by well plate method against Aspergillus flavus,
Chrysosporium keratinophilum and Candida albicans (MTCC 227). Normal saline was used to make a suspension of spore of fungal strains for
lawning.42 A loop full of particular fungal strain was transferred to 3 ml saline to get a suspension of corresponding species. Twenty milliliters of
agar media were poured into each Petri dish. Excess of suspension was decanted and plates were dried by placing in an incubator at 37 ˚C for 1
h. Using sterile cork borer punched carefully, wells were made on these seeded agar plates different concentrations of the test compounds in
DMSO were added into each labeled well. A control was also prepared for the plates in the same way using solvent DMSO. The Petri dishes
were prepared in triplicate and maintained at 25 ˚C for 72 h. Antifungal activity was determined by measuring the diameter of inhibition zone.
The activity of each compound was compared with fluconazole as standard. The MIC and MFC (Minimum Fungicidal Concentration) was
determined by broth micro dilution method. The nutrient broth, which contained logarithmic serially twofold diluted amount of test compounds
and controls, was inoculated with approximately 1.6 X 104 ꢀ 6 104 c.f.u/ml was used. The cultures were incubated for 48h at 35° C and the
X
growth was monitored. The lowest concentration (highest dilution) required to arrest the fungus growth was regarded as MIC (Minimum
Inhibitory Concentration). To obtain MFC (Minimum Fungicidal Concentration), 0.1 ml volume was taken from each tube and spread on agar
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plates. The number of c.f.u. was counted after 48 h of incubation at 35° C. MFC was defined as the lowest drug concentration at which 99.9% of
the inoculum was killed. The experiments were performed in triplicates.
The antibacterial activity evaluation of newly synthesized compounds (5a-k) and (6a-e) revealed that, most of the tested compounds exhibited
moderate to very good antibacterial activity against all the tested different strains.(Table 2 and 3) Among them, the compounds 5d, 5h, 5i, 5j,
5k, 6b and 6d exhibited very good activities against all four tested bacterial strains namely Escherichia coli (ZOI = 14ꢀ19 mm and MIC = 3.12ꢀ
6.25 µg/ml), Staphylococcus aureus (ZOI = 13ꢀ17 mm and MIC = 3.15ꢀ12.5 µg/ml), Pseudomonas aeruginosa (ZOI = 12ꢀ17 mm and MIC =
3.13ꢀ12.5 µg/ml) and Bacillus subtilis (ZOI = 13ꢀ16 mm and MIC = 3.12ꢀ6.5 µg/ml) with respect to the standard drug Ciproflaxin (ZOI = 17ꢀ24
mm and MIC = 3.10ꢀ3.25 µg/ml against all strains) at 0.5 ꢀ1 mg/ml concentration. Similarly the derivatives 5b, 5c, 5e, 5f, 6c and 6e shown good
activities against tested two gram positive and two gram negative bacterial strains namely Escherichia coli (ZOI = 11ꢀ17 mm and MIC = 6.12ꢀ
12.5 µg/ml), Staphylococcus aureus (ZOI = 6ꢀ17 mm and MIC = 7.15ꢀ13.2 µg/ml), Pseudomonas aeruginosa (ZOI = 9ꢀ15 mm and MIC = 6.25ꢀ
12.5 µg/ml) and Bacillus subtilis (ZOI = 9ꢀ16 mm and MIC = 6.25ꢀ14.2 µg/ml) when compared to the standard drug Ciproflaxin. The
compounds 5a, 5g and 6a were nonꢀsignificant with ZOI = 07ꢀ15 mm and MIC = 6.25ꢀ25 µg/ml as it shows moderate inhibitory activity towards
the panel of human pathogens.
Table 2
Table 3
Among the newly synthesized compounds (5a-k) and (6a-e) most of the compounds ViienwhAirbticileteOdnlinethe growth of most of the human pathogenic
DOI: 10.1039/C6RA22705H
fungi tested (Table 4 and 5). The sensitivity of the fungal strains varies according to the species. Among the tested fungi, Candida albicans was
highly sensitive compared to the other fungi species. Aspergillus flavus and Chrysosporium keratinophilum showed some differing responses to
each organic compound. The compounds 5i, 5j and 6d showed very good activity against tested fungal strains Aspergillus flavus with ZOI = 9ꢀ
12 mm and MIC = 7.7 – 7.9 µg/ml with MFC = 16.1 ꢀ 16.8 µg/ml, Chrysosporium keratinophilum with ZOI = 13ꢀ15 mm and MIC = 8.15 – 8.49
µg/ml with MFC = 16.6 ꢀ 17.9 µg/ml and Candida albicans with ZOI = 15ꢀ18 mm and MIC = 4.95 – 5.35 µg/ml with MFC = 7.38 ꢀ 7.75 µg/ml
respectively when compared standard drug Flucanazole with ZOI = 12ꢀ22 mm and MIC = 3.12 – 6.25 µg/ml with MFC = 6.18 ꢀ 12.7 µg/ml
against all the tested strains at 0.5 – 1 mg/ml concentration. On the other hand, derivatives 5b, 5e, 5f, 5h, 5k, 6b and 6c shown good activity with
tested fungal strains Aspergillus flavus (ZOI = 8ꢀ12 mm and MIC = 8.35 – 8.73 µg/ml with MFC = 18.3 ꢀ 19.2 µg/ml), Chrysosporium
keratinophilum (ZOI = 11ꢀ14 mm and MIC = 8.7 – 9.15 µg/ml with MFC = 18.9 ꢀ 19.9 µg/ml) and Candida albicans (ZOI = 13ꢀ16 mm and
MIC = 6.85 – 7.95 µg/ml with MFC = 11.8 ꢀ 12.8 µg/ml) against the standard drug Flucanazole with the tested fungal strains. The rest of the
synthesized compounds failed to show good and comparable antifungal activity with ZOI = 5ꢀ12 mm and MIC = 10.5 – 25.8 µg/ml with MFC =
50 ꢀ 100 µg/ml against the panel of tested fungal strains when compared to the standard drug fluconazole.
Table 4
Table 5
Further, the structureꢀactivity relationship of the compounds (5a-k) and (6a-e) revealed that the compounds 5d, 5h, 5i, 5j, 5k, 6b and 6d
containing 3,4ꢀdimethyl phenyl, 2ꢀfluoro phenyl, 2ꢀchloro phenyl, 3ꢀpyridyl, 4ꢀthiomethyl phenyl, 1ꢀ(phenyl)ꢀ3ꢀ(4ꢀchloro phenyl)ꢀ1Hꢀpyrazole
and 1ꢀ(4ꢀchloro phenyl)ꢀ3ꢀ(3ꢀbromo phenyl)ꢀ1Hꢀpyrazole substituent’s at the 3rd position of propꢀ2ꢀenꢀ1ꢀone (chalcone) moiety respectively
were found to exhibit enhanced antiꢀbacterial activity compared to the less or unsubstituted phenyl derivatives. (i.e. like 5a, 6a) against the
standard drug Ciproflaxin. While the derivatives 5i, 5j and 6d also found to exhibit enhanced antiꢀfungal activities against tested fungal strains
compared to standard drug Fluconazole. Similarly the molecules 5b, 5c, 5e, 5f, 5h, 6c and 6e containing 3ꢀchloroꢀ2ꢀfluoro phenyl, 4ꢀhydroxy
phenyl, 4ꢀfluoro phenyl, 4ꢀchloro phenyl, 2ꢀfluoro phenyl, 1ꢀ(4ꢀchloro phenyl)ꢀ3ꢀ(phenyl)ꢀ1Hꢀpyrazole, 1ꢀ(phenyl)ꢀ3ꢀ(3ꢀbromo phenyl)ꢀ1Hꢀ
pyrazole groups respectively at 3rd postion of chalcone were found to exhibit good antimicrobial activities. Further SAR, reveals that the electron
donating groups like methyl, thiomethyl, pyridyl and electron donating groups like chloro, fluoro in the molecules at different positions were
generally more beneficial than the unsubstituted ones.
2.2.2. In-vitro anti-oxidant activity
In order to investigate the possible biological studies for the synthesized compounds (5a-k) and (6a-e), were also screened for their inꢀvitro
antioxidant activity by 1,1ꢀdiphenylꢀ2ꢀpicrylhydrazyl (DPPH) radical scavenging method using Ascorbic acid as standard drug.43 The
spectrophotometric assay uses the stable radical DPPH as a reagent.
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RSC Advances
21 mg of DPPH was dissolved with methanol in 100ml volumetric flask to get DPPH Stock solution. Further, 18 ml of above DPPH stock
solution was pipette out into a 100ml volumetric flask and diluted with methanol to obtain 100 µM DPPH working solution.
The sample solution was prepared by mixing 1ml of various concentrations of the test compounds (5a-n) (62.5µg/ml, 31.25µg/ml,
15.62µg/ml) in DMSO with 5ml DPPH working solution (100µM) in each test tube. 1ml of DMSO was taken in a test tube and then 5ml of
DPPH working solution (100µM) was added and kept as control sample. 1ml of DMSO was taken in a test tube and then 5ml of methanol was
added and kept as blank. These test tubes were incubated at 37°C for 20min and the absorbance was determined by using UV spectrophotometer
at 517nm.The % inhibition was calculated by using formula,
% Inhibition = [(Abscontrol – Abssample)/Abscontrol] × 100
Where, Abscontrol is the absorbance of the control reaction (containing all reagents, except the test compound) and Abssample is the absorbance of
the test compound. Tests were carried at in triplicates. The IC50 value was obtained by plotting the graph, taking % inhibition on yꢀ axis and
concentration on xꢀ axis.43
The antiꢀoxidant activity of the compounds (5a-k) and (6a-e) were further evaluated by ABTS (2,2’ꢀ azino bis (3ꢀethyl benzothiazolineꢀ6ꢀ
sulfonic acid) antioxidant assay method by bleaching of ABTS derived radical cations. The radical cation derived from ABTS was prepared by
reaction of 0.06 ml ABTS with 3 ml MnO2 (25 mg/ml) in 5 ml aqueous buffer solution (pH 7). After shaking the solution for a few minutes, it
was centrifuged and filtered. The absorbance (Acontrol) of the resulting greenꢀblue solution (ABTS radical solution) was recorded at γmax = 734
View Article Online
DOI: 10.1039/C6RA22705H
nm. The absorbance (Atest) was measured upon the addition of 0.02 ml of 1mg/ml solution of the tested sample in spectroscopic grade
Methanol/buffer (1:1 v/v) to the ABTS solution. The inhibition ratio (%) was calculated using the following formula:
% Inhibition = [(Acontrol – A test)/ Acontrol] × 100
Ascorbic acid (0.02 ml, 2Mm) solution was used as a standard antiꢀoxidant (positive control). Blank sample was run using solvent without
ABTS.
Evaluation of antioxidant activity revealed that, most of the compounds tested compounds exhibited moderate to excellent DPPH and ABTS
radical scavenging ability compared with the positive control Ascorbic acid. (Table 6) Among the synthesized compounds, compounds 5a, 5d,
5g, 5j, 5k and 6a bearing phenyl, 3,4ꢀdimethyl phenyl, 4ꢀmethoxy phenyl, 3ꢀpyridyl, 4ꢀthiomethyl and 1,3ꢀ(biphenyl)ꢀ1Hꢀpyrazole substituent’s
at the 3rd position of propꢀ2ꢀenꢀ1ꢀone (chalcone) moiety respectively were found to be more effective and potent DPPH radical scavenging
ability with IC50 values 16.36 µM, 15.33 µM, 15.38 µM, 17.48 µM, 16.99 µM and 14.48 µM compared to the standard drug Ascorbic acid with
IC50 value 12.27 µM at 31.5 µg/ml concentration by DPPH radical scavenging activity method. The antiꢀoxidant activity of the derivatives 5a,
5d, 5g, 5j, 5k and 6a were further illustrated by ABTS assay method with 78.5%, 80.4%, 81.2%, 76.9%, 77.8% and 81.8% inhibition against the
positive control Ascorbic acid with 88.5% inhibition. Further the derivatives 5f, 5h, 6b, 6c and 6e containing 4ꢀchloro phenyl, 2ꢀfluoro phenyl,
1ꢀ(phenyl)ꢀ3ꢀ(4ꢀchloro phenyl)ꢀ1Hꢀpyrazole, 1ꢀ(4ꢀchloro phenyl)ꢀ3ꢀ(phenyl)ꢀ1Hꢀpyrazole and 1ꢀ(phenyl)ꢀ3ꢀ(3ꢀbromo phenyl)ꢀ1Hꢀpyrazole
exhibited moderate DPPH radical scavenging activities with IC50 values 43.76 µM, 45.33 µM, 34.91 µM, 45.48 µM and 39.82 µM respectively
with moderate ABTS radical inhibition with 53.1%, 58.6%, 63.5%, 59.7% and 58.6% respectively compared with the positive control Ascorbic
acid. The remaining compounds nonꢀsignificant radical scavenging activity with IC50 values in the range of 50.21ꢀ255.13 µM and 15.8% ꢀ
43.3% inhibition in DPPH method and ABTS assay methods respectively. Generally according to structure activity relationship (SAR), it was
observed that the compounds with less or unsubstitued phenyl at Cꢀ1 and Cꢀ3 of the pyrazole ring like in 6a, electron donating groups like
methyl, methoxy, thiomethyl at Cꢀ3 and Cꢀ4 position of the phenyl ring as in 5d, 5g, 5k and heterocyclic pyridyl on 3rd position of the propꢀ2ꢀenꢀ
1ꢀone (chalcone) (i.e. 5j) moiety were found to possess potent radical scavenging ability than the corresponding electron withdrawing
substituents in phenyl rings (i.e 5b, 5c, 6b, 6c etc).
Table 6
2.2.3. In-vitro anti-cancer activity
Cytotoxicity of all the synthesized compounds were determined on the basis of measurement of in vitro growth inhibition of tumor cell lines in
96 well plates by cellꢀmediated reduction of tetrazolium salt to water insoluble formazan crystals using Doxorubicin as a standard. The
cytotoxicity was assessed against human breast adenocarcinoma cell lines (MCFꢀ7, MDAꢀMBꢀ231) in comparison with nonꢀtumorous breast cell
line MCFꢀ10A ( human mammary epithelial cell line) and nonꢀtumorous VERO cell line (normal monkey kidney epithelial cell line) and using
the standard MTT (3ꢀ(4,5ꢀdimethylꢀ2ꢀthiazolyl)ꢀ2,5ꢀdiphenylꢀ2Hꢀtetrazolium bromide) colorimetric assay.44,45 Estrogen receptor (ER)ꢀpositive
MCFꢀ7 and ER negative MDAꢀMBꢀ231 breast cancer cells, nonꢀtumorous MCFꢀ10A and VERO cell lines were procured from National Centre
5

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for Cell Science (NCCS), Pune, Maharashtra, India. In detail, exponentially growing cells were harvested and seeded in sterile 96 well flat
bottom tissue culture plates at a density of 5000 cells/well and allowed to attach overnight. Test compounds were prepared just prior to the
experiment and serially diluted with suitable medium to get different concentration from 25ꢀ200 µg. The final concentration of DMSO was not
more than 0.05 %. After 24 h of incubation, cells were treated with 100 µl of test compounds for 48 h. After 48h, 50 µl of MTT reagent was
added and incubated for 3h at 37 °C. After 3h of incubation medium along with MTT was aspirated and 200 µl of 100 % DMSO was added to
each well to solubilize the formazan crystals. The optical density was measured by a well plate reader at 540 nm using a well plate reader
(ELx800, BioTek Instruments Inc., Winooski, VT, USA).The IC50 values (50% inhibitory concentration) were calculated from the plotted
absorbance data for the doseꢀresponse curves. IC50 values (in µM) were shown as mean ± SD of three independent experiments.
The newly synthesized 1,2,3ꢀTriazolyl chalcones (5a-k) and (6a-e) as potential anticancer agents were evaluated for their inꢀvitro cytotoxicity
against human breast adenocarcinoma (MCFꢀ7, MDAꢀMBꢀ231) cell lines using the standard MTT assay. From the data reported in Table 7, it
was revealed that the most of compounds were nonꢀtoxic against normal nonꢀtumor cell lines MCFꢀ10A (breast) and VERO and some of them
exhibits good cytotoxic activities against the breast cancer cell lines MCFꢀ7, MDAꢀMBꢀ231. The compounds 5b, 5e, 5f, 6c and 6d exhibits good
cytotoxic activities against both human breast adenocarcinoma cell lines (MCFꢀ7 and MDAꢀMBꢀ231) with IC50 values 10.3 µM, 7.8 µM, 8.3
µM, 8.7 µM and 7.9 µM (for MDAꢀMBꢀ231 cell line) and 3.2 µM , 6.4 µM , 3.1 µM , 3.2 µM and 3.4 µM (for MCFꢀ7 cell line) respectively
compared to the positive control Doxorubicin with IC50 values 1.1 µM (for MCFꢀ7 cell line) and 0.9 µM (for MDAꢀMBꢀ231 cell line)
respectively. On the other hand, compounds 5g and 5k exhibits moderate cytotoxic activities with IC50 values 16.3 µM, 21.3 µM (for MDAꢀMBꢀ
231 cell line) and 5d with 25.6 µM (for MCFꢀ7 cell line) respectively when compared to the standard drug. However, compounds 5b, 5g and 6e
showed equal cytotoxicity on normal nonꢀtumor breast cell line MCFꢀ10A with IC VviewalAurtieclse O2nli3ne.5 µM, 26.7 µM and 36.6 µM respectively.
DOI: 10.1039/C6RA22705H
50
Further the derivatives 5b and 5g exhibited equal cytotoxicity against normal nonꢀtumor VERO cell line with IC50 values 20.9 µM and 25.3 µM
respectively. Similarly the rest of the derivatives were nonꢀsignificant with IC50 values ranging from 30.5 µM to more than 100 µM (for MDAꢀ
MBꢀ231 cell line) and 48.3 µM to more than 100 µM (for MCFꢀ7 cell line) respectively and failed to show good and comparable cytotoxic
activity when compared to the standard drug doxorubicin.
Further, the structureꢀactivity relationship of the compounds (5a-k) and (6a-e) revealed that the compounds 5b, 5e, 5f, 6c and 6d containing 3ꢀ
chloroꢀ2ꢀfluoro phenyl, 4ꢀfluoro phenyl, 4ꢀchloro phenyl, 1ꢀ(4ꢀchloro phenyl)ꢀ3ꢀ(phenyl)ꢀ1Hꢀpyrazole and 1ꢀ(4ꢀchloro phenyl)ꢀ3ꢀ(3ꢀbromo
phenyl)ꢀ1Hꢀpyrazole substituent’s at the 3rd position of propꢀ2ꢀenꢀ1ꢀone (chalcone) moiety respectively were found to exhibit enhanced antiꢀ
cancer activity compared to the less or unsubstituted phenyl derivatives. (i.e. like 5a, 6a) A closer look into the structure activity relationship
suggests that the cytotoxic potency was highly dependent, not surprisingly, on the substitution types and patterns on the phenyl rings. The
different substituents on the phenyl rings attached at the Cꢀ1 and Cꢀ3 of the pyrazole ring like in 6c, 6d and Cꢀ3 of the chalcone moiety as in 5b,
5e, 5f can slightly alter the cytotoxicity against the cancer cell lines tested compared to nonꢀsubstituted analogues (5a, 5b). However, replacing
the hydrogen with an electron withdrawing group on the phenyl ring attached to the Cꢀ3 of the chalcone (as in 5b, 5e, 5f) and Cꢀ1 and Cꢀ3
position of the pyrazole ring (as in 6c, 6d) resulted in a significant activity increase. Also, the results clearly indicate that the halogenated
substitution on the phenyl ring attached to the Cꢀ3 of the chalcone and Cꢀ1 and Cꢀ3 position of the pyrazole ring showed better activity against
the MCFꢀ7 and MDAꢀMBꢀ231 cancer cell lines. (Table 7) Hence, the biological response increased by halogenated analogs than their nonꢀ
halogenated motifs. This is probably due to enhanced lipophilicity, pharmacokinetic properties, physicochemical properties, endurance for
metabolic destruction and electronegativity of the molecules due to presence of halo substituents like chloro, fluoro etc. as shown by earlier
literature studies on halogen containing molecules.46,47
Table 7
3. Conclusion
In conclusion, a series of new series of novel (2E)ꢀ1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ꢀ3ꢀ
aryl propꢀ2ꢀenꢀ1ꢀone (5a-k) and (2E)ꢀ1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ꢀ3ꢀ(1,3ꢀdiarylꢀ1Hꢀ
pyrazolꢀ4ꢀyl)propꢀ2ꢀenꢀ1ꢀone (6a-e) were synthesized via
a
ClaisenꢀSchmidt condensation of 1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ
(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ethanone (4) with different aryl and 1,3ꢀdiarylꢀ1Hꢀpyrazoleꢀ4ꢀcarbaldehydes iii(a-e) in
presence of ethanol and sodium hydroxide mixture in quantitative yields and evaluated for their inꢀvitro antimicrobial, antiꢀoxidant and antiꢀ
cancer studies. Among the series, compounds 5b, 5e, 5f, 5i, 5j, 5k, 6c and 6d were found to be potent and broad spectrum antiꢀmicrobial agents
comparable with respect to the standard drug Ciproflaxin and Flucanazole respectively. While the compounds 5c, 5d, 5h and 6b were found to
be good antiꢀbacterial agents and compounds 6e and 6b were found to be good antiꢀfungal agents against the standard drugs. Similarly
derivatives 5a, 5d, 5g, 5j, 5k and 6a were found to exhibit good antiꢀoxidant properties against the standard ascorbic acid. Antiꢀcancer studies
revealed that, the compounds 5b, 5e, 5f, 6c and 6d has shown good cytotoxic activity against the human breast adenocarcinoma cell lines
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RSC Advances
(MCFꢀ7 and MDAꢀMBꢀ231) with respect to the positive control Doxorubicin. The significant antiꢀmicrobial and antiꢀcancer activities of the
synthesized compounds may be due to the presence of the electronꢀdonating and halo substituted groups on the phenyl rings along with core
1,2,3ꢀtriazole, chalcone and pyrazole moiety. Furthermore, the observed antiꢀmicrobial and antiꢀcancer activities may be looked at as key steps
for designing more potent new chemical entities with comparable pharmacological profiles to that of the standard drugs.
4. Experimental
4.1. General
All solvents used were of analytical grade and the reagents were used was purchased. All melting points were determined by open capillary
1
method and were uncorrected. IR spectra were obtained in KBr disc on a Shimadzu FTꢀIR 157 spectrometer. H NMR spectra were recorded
either on a PerkinꢀElmer EMꢀ390 or on a Bruker WHꢀ200 (400 MHz) in CDCl3 or DMSOꢀd6 as solvent, using tetramethylsilane (TMS) as an
internal standard and chemical shifts and coupling constants were expressed as δ (ppm) and Hz respectively. Mass spectrum was determined on
a Jeol SX 102/Daꢀ600 mass spectrometer/ Data System using Argon/Xenon (6KV, 10 mA0) as the FAB gas. The accelerating voltage was 10 KV
and spectra were recorded at room temperature. The elemental analyses (CHN) were performed on using VARIO ELꢀIII (Elementar
Analysensysteme GmBH). The progresses of the reactions were monitored by TLC on preꢀcoated silica gel G plates. All the spectral data’s of
newly synthesized compounds were consistent with proposed structure and microanalysis within ± 0.4 of the calculated values.
4.2. General procedure for the synthesis of 1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-
yl}ethanone (4)
View Article Online
DOI: 10.1039/C6RA22705H
The solution of 3ꢀazidoꢀ1,2ꢀdichloroꢀ4ꢀmethylꢀ5ꢀ(trifluoromethyl) benzene (3) (0.01 mol) in methanol was added slowly to solution of sodium
0
methoxide (0.015 mol) in methanol at 0ꢀ5 0C. To this reaction mass, acetyl acetone (0.012 mol) was added slowly at 0ꢀ5 C. The reaction mass
0
was stirred at 25ꢀ30 C for 12 hrs. The completion of reaction was monitored by TLC. After completion of the reaction, the reaction mixture
was quenched to pre cooled water while pale brown precipitation observed and the precipitated solid was filtered, washed with water, dried and
recrystallized from ethanol to get pure compound (4).
IR (KBr) γ/cmꢀ1: 2923 (ArꢀH), 1670 (C=O), 1582 (C=N), 1086 (C–F) and 841 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.05 (s, 3H, CH3 of
triazole), 2.40 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 2.77 s, 3H, CH3 of acetyl), 7.98 (s, 1H, ArꢀH of 2,3ꢀdichloroꢀ5ꢀ
trifluoromethylꢀ6ꢀmethyl phenyl). 13C NMR: (100 MHz, CDCl3, δ ppm): 9.03 (CH3 of triazole), 14.25 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀ
methyl phenyl), 27.82 (CH3 of acetyl), 121.24, 123.97, 129.9, 132.2, 135.1, 135.6, 136.0, 138.9, 143.3, 194.0 (C=O of acetyl). 13C NMRꢀDEPTꢀ
135 (100 MHz, CDCl3, δ ppm): 9.03 (CH3 of triazole), 14.25 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 27.82 (CH3 of acetyl),
129.9. MS: m/z = 352 (M+), 354 (M++2). Anal. calcd. for C13H10Cl2F3N3O: C (44.34%), H (2.86%), N (11.93%). Found: C (44.28%), H (2.81%),
N (11.96%).
4.3. General procedure for the synthesis of (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-
3-aryl prop-2-en-1-one (5a-k) and (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(1,3-
diaryl-1H-pyrazol-4-yl)prop-2-en-1-one (6a-e)
A mixture of 1ꢀ{1ꢀ[2,3ꢀdichloroꢀ6ꢀmethylꢀ5ꢀ(trifluoromethyl)phenyl]ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ethanone (4) (0.01 mol), sodium hydroxide
0
(0.02 mol) solution (25% in water) and aryl aldehydes (0.01 mol)/ iii(a-e) in methanol was stirred for 12 hrs at 25ꢀ30 C. The completion of
reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched to pre cooled water while precipitation
observed and the precipitated solid was filtered, washed with water, dried and recrystallized from ethanol to get pure compound (5a-k) and (6a-
e) respectively.
4.3.1. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-phenyl prop-2-en-1-one (5a)
IR (KBr) γ/cmꢀ1: 2930 (ArꢀH), 1665 (C=O), 1582 (C=N), 1087 (C–F) and 836 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.07 (s, 3H, CH3 of
triazole), 2.45 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 6.94 (d, 2H, J = 8.0 Hz, ArꢀH of Phenyl), 7.02ꢀ7.92 (m, 5H, ArꢀH
of Phenyl and CH=CH), 7.96 (s, 1H, ArꢀH of 2,3ꢀdichloroꢀ6ꢀtrifluoromethyl Phenyl). 13C NMR: (100 MHz, CDCl3, δ ppm): 9.18 (CH3 of
triazole), 14.27 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 112.2, 120.21, 120.78, 123.3, 125.8, 128.7, 129.9, 131.5, 134.6, 135.8,
13
138.4, 140.3, 142.1, 144.2, 145.3, 161.2, 184.0 (C=O of Chalcone). C NMRꢀDEPTꢀ135 (100 MHz, CDCl3, δ ppm): 9.18 (CH3 of triazole),
14.27 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 112.1, 120.2, 128.6, 129.7, 131.4, 142.4. MS: m/z = 440 (M+), 442 (M++2).
Anal. calcd. for C20H14Cl2F3N3O: C (54.56%), H (3.21%), N (9.54%).Found: C (54.58%), H (3.24%), N (9.58%).
4.3.2. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(3-chloro-2-fluoro phenyl) prop-2-
en-1-one (5b)
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IR (KBr) γ/cmꢀ1: 2935 (ArꢀH), 1667 (C=O), 1584 (C=N), 1085 (C–F) and 833 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.09 (s, 3H, CH3 of
triazole), 2.48 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 7.42 (d, 1H, J = 8.2 Hz, ArꢀH of 3ꢀchloroꢀ2ꢀfluoro phenyl), 7.55
(d, 1H, J = 8.2 Hz, ArꢀH of 3ꢀchloroꢀ2ꢀfluoro phenyl), 7.89 (d, 2H, J = 8.0 Hz, CH=CH), 7.95 (s, 1H, ArꢀH of 2,3ꢀdichloroꢀ6ꢀtrifluoromethyl
13
Phenyl). C NMR: (100 MHz, CDCl3, δ ppm): 9.17 (CH3 of triazole), 14.25 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 112.21,
120.23, 120.77, 123.33, 125.82, 128.72, 129.93, 131.54, 134.6, 135.81, 138.43, 140.31, 142.11, 144.23, 145.32, 161.4, 184.3 (C=O of
Chalcone). MS: m/z = 490 (M+), 492 (M++2). Anal. calcd. for C20H12Cl2F4N3O: C (48.76%), H (2.45%), N (8.53%).Found: C (48.78%), H
(2.44%), N (8.55%).
4.3.3. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(4-hydroxy phenyl) prop-2-en-1-one
(5c)
IR (KBr) γ/cmꢀ1: 3068 (ArꢀH), 1663 (C=O), 1566 (C=N), 1168 (C–F) and 713 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.10 (s, 3H, CH3 of
triazole), 2.52 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 3.85 (s, 1H, ꢀOH), 6.96 (d, 2H, J= 8.4 Hz, ArꢀH of 4ꢀhydroxy
phenyl), 7.70 (d, 2H, J = 8.2 Hz, ArꢀH of 4ꢀhydroxy phenyl), 7.96 (d, 1H, J= 16 Hz, CH=CH), 7.98 (d, 1H, J= 16 Hz, CH=CH), 8.0 (s, 1H, ArꢀH
of 2,3ꢀdichloroꢀ6ꢀtrifluoromethyl phenyl). 13C NMR (100 MHz, CDCl3, δ ppm): 9.24 (CH3 of triazole), 14.33 (CH3 of 2,3ꢀdichloroꢀ5ꢀ
trifluoromethylꢀ6ꢀmethyl phenyl), 114.42, 120.26, 121.27, 124.03, 126.72, 127.55, 129.8, 130.65, 132.17, 135.74, 136.15, 139.87, 143.84,
144.16, 161.82, 183.20 (C=O of Chalcone). MS: m/z = 455.1 (M+), 457.1 (M++2). Anal. calcd. for C20H14Cl2F3N3O2: Calculated: C(52.65%),
H(3.09%), N(9.21%) ; Found C(52.62%), H(3.08%), N(9.25%).
4.3.4. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,V3ie-wtArritiaclezOonlli-n4e -yl}-3-(3,4-dimethyl phenyl) prop-2-en-1-
DOI: 10.1039/C6RA22705H
one (5d)
IR (KBr) γ/cmꢀ1: 3065 (ArꢀH), 1667 (C=O), 1568 (C=N), 1165 (C–F) and 711 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.09 (s, 3H, CH3 of
triazole), 2.33 (s, 3H, CH3 of 3,4ꢀdimethyl phenyl), 2.40 (s, 3H, CH3 of 3,4ꢀdimethyl phenyl), 2.59 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀ
trifluoromethylꢀ6ꢀmethyl phenyl), 7.26 (d, 1H, J= 8.4 Hz, ArꢀH of 3,4ꢀdimethyl phenyl), 7.39 (d, 1H, J = 8.2 Hz, ArꢀH of 3,4ꢀdimethyl phenyl),
7.59ꢀ7.65 (d, 1H, J= 23.2 Hz, CH=CH), 7.81 (s, 1H, ArꢀH of 3,4ꢀdimethyl phenyl), 7.94ꢀ8.00 (d, 1H, J= 23.0 Hz, CH=CH), 8.04 (s, 1H, ArꢀH of
2,3ꢀdichloroꢀ6ꢀtrifluoromethyl phenyl). 13C NMR (100 MHz, CDCl3, δ ppm): 8.20 (CH3 of triazole), 13.28, 14.28 (2CH3 of 3,4ꢀdimethyl
phenyl), 20.83 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 114.42, 120.26, 121.27, 124.03, 126.72, 127.55, 129.8, 130.65, 132.17,
135.74, 136.15, 139.87, 143.84, 144.16, 161.82, 183.4 (C=O of Chalcone). MS: m/z = 468.1 (M+), 470.1 (M++2). Anal. calcd. for
C22H18Cl2F3N3O: Calculated: C(56.42%), H(3.87%), N(8.97%) ; Found C(56.40%), H(3.85%), N(8.92%).
4.3.5 (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(4-fluoro phenyl) prop-2-en-1-one
(5e)
IR (KBr) γ/cmꢀ1: 3065 (ArꢀH), 1662 (C=O), 1564 (C=N), 1166 (C–F) and 712 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.09 (s, 3H, CH3 of
triazole), 2.50 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 7.33ꢀ7.36 (dd, 2H, J= 6.4 Hz, 2.4 Hz, ArꢀH of 4ꢀfluoro phenyl),
7.45ꢀ7.47 (dd, 1H, J = 6.4 Hz, 2.4 Hz, ArꢀH of 4ꢀfluoro phenyl), 7.89ꢀ7.92 (dd, 1H, J = 6.8 Hz, 2.0 Hz, ArꢀH of 4ꢀfluoro phenyl), 8.0 (s, 1H, Arꢀ
H of 2,3ꢀdichloroꢀ6ꢀtrifluoromethyl phenyl), 8.08ꢀ8.12 (d, 1H, J = 16 Hz, CH=CH), 8.37ꢀ8.41 (d, 1H, J = 16 Hz, CH=CH). 13C NMR (100 MHz,
CDCl3, δ ppm): 9.25 (CH3 of triazole), 14.30 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 114.40, 120.29, 121.30, 124.06, 126.74,
127.55, 129.83, 130.64, 132.15, 135.71, 136.12, 139.82, 143.81, 144.19, 161.85, 183.4 (C=O of Chalcone). MS: m/z = 459.3 (M+), 461.3
(M++2). Anal. calcd. for C20H13Cl2F4N3O: Calculated: C(52.42%), H(2.86%), N(9.17%) ; Found C(52.42%), H(2.88%), N(9.19%).
4.3.6 (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(4-chloro phenyl) prop-2-en-1-one
(5f)
IR (KBr) γ/cmꢀ1: 3067 (ArꢀH), 1668 (C=O), 1567 (C=N), 1169 (C–F) and 715 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.09 (s, 3H, CH3 of
triazole), 2.59 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 7.26ꢀ7.39 (d, 2H, J= 8.2 Hz, ArꢀH of 4ꢀchloro phenyl), 7.52ꢀ7.65
(d, 2H, J = 8.0 Hz, ArꢀH of 4ꢀchloro phenyl), 7.81 (s, 1H, ArꢀH of 2,3ꢀdichloroꢀ6ꢀtrifluoromethyl phenyl), 7.94ꢀ8.00 (d, 1H, J = 23 Hz,
13
CH=CH), 8.00ꢀ8.46 (d, 1H, J = 17 Hz, CH=CH). C NMR (100 MHz, CDCl3, δ ppm): 8.20 (CH3 of triazole), 14.28 (CH3 of 2,3ꢀdichloroꢀ5ꢀ
trifluoromethylꢀ6ꢀmethyl phenyl), 114.38, 120.17, 121.28, 124.03, 126.72, 127.52, 129.80, 130.62, 132.11, 135.68, 136.10, 139.79, 143.79,
144.18, 161.84, 183.40 (C=O of Chalcone). MS: m/z = 473.1 (M+), 475.1 (M++2). Anal. calcd. for C20H13Cl3F3N3O: Calculated: C(50.60%),
H(2.76%), N(8.85%) ; Found C(50.62%), H(2.78%), N(8.82%).
4.3.7 (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(4-methoxy phenyl) prop-2-en-1-one
(5g)
IR (KBr) γ/cmꢀ1: 2932 (ArCH=CH), 2893(CH=CH), 1668 (C=O), 1089 (C–F) and 713 (C–Cl). 1H NMR (400 MHz, CDCl3, δ ppm): 2.09 (s, 3H,
of triazole), 2.50 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 3.86 (s, 3H, OCH3 of 4ꢀmethoxy phenyl), 6.94 (d, 2H, J = 8.6
8

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RSC Advances
Hz, ArH of 4ꢀmethoxy phenyl ), 7.69 (d, 2H, J = 8.2 Hz, ArH of 4ꢀmethoxy phenyl), 7.92ꢀ7.96 (d, 1H, J = 15.8 Hz, CH=CH), 7.98ꢀ8.02 (d, 1H,
J = 15.8 Hz, CH=CH), 8.00 (s, 1H, ArH of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl). 13C NMR (100 MHz, CDCl3, δ ppm): 9.25 (CH3 of
triazole), 14.32 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 55.42 (OCH3 of 4ꢀmethoxy phenyl), 114.43, 120.28, 121.28, 124.01,
126.74, 127.56, 129.9, 130.67, 132.18, 135.76, 136.13, 139.85, 143.83, 144.17,161.8, 184.0 (C=O of Chalcone). 13C NMRꢀDEPTꢀ135 (100
MHz, CDCl3, δ ppm): 9.25(CH3 of triazole), 14.32 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 55.44 (OCH3 of 4ꢀmethoxy
phenyl), 114.44, 120.29, 129.90, 130.69, 144.19. MS: m/z = 468 (M+), 470 (M++2). Anal. calcd. for C21H16Cl2F3N3O2: C (53.63%), H (3.43%),
N (8.94%). Found:C (53.56%), H (3.47%), N (8.98%).
4.3.8. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(2-fluoro phenyl) prop-2-en-1-one
(5h)
IR (KBr) γ/cmꢀ1: 3080 (ArꢀH), 1665 (C=O), 1563 (C=N), 1163 (C–F) and 712 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.10 (s, 3H, CH3 of
triazole), 2.51 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 7.34ꢀ7.37 (t, 2H, J= 8.2 Hz, ArꢀH of 2ꢀfluoro phenyl), 7.46ꢀ7.48
(dd, 1H, J = 6.4 Hz, 2.4 Hz, ArꢀH of 2ꢀfluoro phenyl), 7.88ꢀ7.91 (dd, 1H, J = 6.8 Hz, 2.0 Hz, ArꢀH of 2ꢀfluoro phenyl), 8.01 (s, 1H, ArꢀH of 2,3ꢀ
dichloroꢀ6ꢀtrifluoromethyl phenyl), 8.07ꢀ8.11 (d, 1H, J = 16 Hz, CH=CH), 8.36ꢀ8.40 (d, 1H, J = 16 Hz, CH=CH). 13C NMR (100 MHz, CDCl3,
δ ppm): 9.24 (CH3 of triazole), 14.29 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 114.40, 120.28, 121.34, 124.08, 126.75, 127.53,
129.81, 130.62, 132.13, 135.69, 136.10, 139.83, 143.82, 144.17, 161.84, 184.01 (C=O of Chalcone). MS: m/z = 460.2 (M+), 462.2 (M++2). Anal.
calcd. for C20H13Cl2F4N3O: Calculated: C(52.42%), H(2.86%), N(9.17%) ; Found C(52.43%), H(2.89%), N(9.19%).
4.3.9. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(2-chloro phenyl) prop-2-en-1-one
View Article Online
(5i)
DOI: 10.1039/C6RA22705H
IR (KBr) γ/cmꢀ1: 3077 (ArꢀH), 1667 (C=O), 1566 (C=N), 1167 (C–F) and 715 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.09 (s, 3H, CH3 of
triazole), 2.51 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 7.33ꢀ7.36 (t, 2H, J= 8.0 Hz, ArꢀH of 2ꢀchloro phenyl), 7.44ꢀ7.47
(d, 1H, J = 8.0 Hz, ArꢀH of 2ꢀchloro phenyl), 7.86ꢀ7.88 (d, 1H, J = 8.0 Hz, ArꢀH of 2ꢀchloro phenyl), 7.99 (s, 1H, ArꢀH of 2,3ꢀdichloroꢀ6ꢀ
13
trifluoromethyl phenyl), 8.06ꢀ8.10 (d, 1H, J = 16 Hz, CH=CH), 8.37ꢀ8.41 (d, 1H, J = 16 Hz, CH=CH). C NMR (100 MHz, CDCl3, δ ppm):
9.26 (CH3 of triazole), 14.29 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 114.37, 120.19, 121.25, 124.01, 126.74, 127.51, 129.78,
130.61, 132.11, 135.66, 136.12, 139.76, 143.76, 144.19, 161.81, 183.20 (C=O of Chalcone). MS: m/z = 474.1 (M+), 476.1 (M++2). Anal. calcd.
for C20H13Cl3F3N3O: Calculated: C(50.60%), H(2.76%), N(8.85%) ; Found C(50.64%), H(2.79%), N(8.83%).
4.3.10. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(3-pyridyl) prop-2-en-1-one (5j)
IR (KBr) γ/cmꢀ1: 3067 (ArꢀH), 1668 (C=O), 1567 (C=N), 1169 (C–F) and 715 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.10 (s, 3H, CH3 of
triazole), 2.50 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 7.33ꢀ7.35 (d, 2H, J= 8.2 Hz, ArꢀH of 3ꢀpyridyl), 7.46ꢀ7.49 (t, 1H,
J = 8.0 Hz, ArꢀH of pyridyl), 7.94 (s, 1H, ArꢀH of pyridyl), 8.01 (s, 1H, ArꢀH of 2,3ꢀdichloroꢀ6ꢀtrifluoromethyl phenyl), 8.07ꢀ8.11 (d, 1H, J = 16
Hz, CH=CH), 8.38ꢀ8.42 (d, 1H, J = 16 Hz, CH=CH). 13C NMR (100 MHz, CDCl3, δ ppm): 9.24 (CH3 of triazole), 14.30 (CH3 of 2,3ꢀdichloroꢀ5ꢀ
trifluoromethylꢀ6ꢀmethyl phenyl), 114.37, 120.18, 121.29, 124.07, 126.75, 127.51, 129.79, 130.61, 132.10, 135.69, 139.77, 143.78, 144.17,
161.81, 183.15 (C=O of Chalcone). MS: m/z = 440.1 (M+), 442.1 (M++2). Anal. calcd. for C19H13Cl2F3N4O: Calculated: C(51.72%), H(2.97%),
N(12.70%) ; Found C(51.67%), H(2.99%), N(12.76%).
4.3.11. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(4-thiomethyl phenyl) prop-2-en-1-
one (5k)
IR (KBr) γ/cmꢀ1: 3070 (ArꢀH), 1667 (C=O), 1568 (C=N), 1171 (C–F) and 710 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.02 (s, 3H, CH3 of
triazole), 2.43 (s, 3H, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 3.43 (s, 3H, SCH3 of 4ꢀthiomethyl phenyl) 7.20ꢀ7.47 (d, 2H, J =
8.0 Hz, ArꢀH of 4ꢀthiomethyl phenyl), 7.58ꢀ7.60 (d, 2H, J = 8.2 Hz, ArꢀH of 4ꢀthiomethyl phenyl), 7.84ꢀ7.88 (d, 1H, J = 15 Hz, CH=CH), 7.93
(s, 1H, ArꢀH of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 7.97ꢀ8.01 (d, 1H, J = 16 Hz, CH=CH). 13C NMR: (100 MHz, CDCl3, δ ppm):
9.25 (CH3 of triazole), 14.32 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 55.42 (SCH3 of 4ꢀthiomethyl phenyl), 114.34, 120.18,
121.23, 124.05, 126.75, 127.52, 129.75, 130.65, 132.14, 135.62, 136.10, 139.73, 143.71, 144.17, 161.80, 183.9 (C=O of Chalcone). MS: m/z =
484.1 (M+), 486.0 (M++2). Anal. calcd. for C21H16Cl2F3N3OS: Calculated: C(51.86%), H(3.32%), N(8.64%) ; Found C(51.90%), H(3.35%),
N(8.70%).
4.3.12.
(2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(1,3-diphenyl-1H-pyrazol-4-yl)
prop-2-en-1-one (6a)
IR (KBr) γ/cmꢀ1: 3068 (ArꢀH), 1664 (C=O), 1565 (C=N), 1164 (C–F) and 712 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.09 (s, 3H, CH3 of
2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 2.49 (s, 3H, CH3 of triazole), 7.34ꢀ7.38 (t, 1H, J = 7.6 Hz, ArꢀH of phenyl), 7.45ꢀ7.53 (m, 5H,
ArꢀH of phenyl), 7.73ꢀ7.76 (dd, 2H, J = 8.2 Hz, 3.2 Hz, ArꢀH of phenyl), 7.82ꢀ7.84 (d, 2H, J = 8.0 Hz, ArꢀH of phenyl), 7.96ꢀ8.00 (d, 1H, J =
9

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Page 10 of 23
16.2 Hz, CH=CH), 8.01 (s, 1H, ArꢀH of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 8.04ꢀ8.08 (d, 1H, J = 16.0 Hz, CH=CH), 8.53 (s, 1H,
ArꢀH of pyrazole). 13C NMR: (400 MHz, CDCl3, δ ppm): 9.23 (CH3 of triazole), 14.31 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl),
118.34, 119.42, 121.88, 126.69, 127.33, 128.72, 128.83, 129.63, 129.95, 130.00, 132.15, 132.24, 135.05, 135.23, 136.12, 139.46, 143.72,
154.36, 183.73 (C=O of Chalcone). MS: m/z = 582.1 (M+), 583.2 (M++1). Anal. calcd. for C29H20Cl2F3N5O: Calculated: C(59.81%), H(3.46%),
N(12.02%) ; Found C(59.75%), H(3.43%), N(12.06%).
4.3.13. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(1-(phenyl)-3-(4-chloro phenyl)-
1H-pyrazol-4-yl) prop-2-en-1-one (6b)
IR (KBr) γ/cmꢀ1: 3069 (ArꢀH), 1665 (C=O), 1567 (C=N), 1162 (C–F) and 711 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.09 (s, 3H, CH3 of
2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 2.49 (s, 3H, CH3 of triazole), 7.35ꢀ7.39 (t, 1H, J = 7.6 Hz, ArꢀH of phenyl), 7.47ꢀ7.54 (q, 4H, J
= 8.2 Hz, 7.6 Hz, ArꢀH of phenyl), 7.68ꢀ7.70 (d, 2H, J = 8.4 Hz, ArꢀH of 4ꢀchloro phenyl), 7.80ꢀ7.82 (d, 2H, J = 8.0 Hz, ArꢀH of 4ꢀchloro
phenyl), 7.94ꢀ7.98 (d, 1H, J = 16.0 Hz, CH=CH), 7.99 (s, 1H, ArꢀH of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 8.00ꢀ8.04 (d, 1H, J =
13
16.0 Hz, CH=CH), 8.51 (s, 1H, ArꢀH of pyrazole). C NMR: (400 MHz, CDCl3, δ ppm): 9.22 (CH3 of triazole), 14.32 (CH3 of 2,3ꢀdichloroꢀ5ꢀ
trifluoromethylꢀ6ꢀmethyl phenyl), 118.33, 119.41, 121.86, 126.68, 127.34, 128.73, 128.81, 129.61, 129.93, 130.02, 132.13, 132.22, 135.03,
135.21, 136.11, 139.44, 143.70, 154.34, 183.72 (C=O of Chalcone). MS: m/z = 615.2 (M+), 616.2 (M++1). Anal. calcd. for C29H19Cl3F3N5O:
Calculated: C(56.47%), H(3.10%), N(11.35%) ; Found C(56.50%), H(3.13%), N(11.32%).
4.3.14. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1V,2iew,3Ar-tticrleiOanzlinoel-4-yl}-3-(1-(4-chloro phenyl)-3-(phenyl)-
DOI: 10.1039/C6RA22705H
1H-pyrazol-4-yl) prop-2-en-1-one (6c)
IR (KBr) γ/cmꢀ1: 3067 (ArꢀH), 1663 (C=O), 1565 (C=N), 1163 (C–F) and 713 (C–Cl). 1HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.10 (s, 3H, CH3 of
2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 2.50 (s, 3H, CH3 of triazole), 7.34ꢀ7.38 (t, 1H, J = 7.6 Hz, ArꢀH of phenyl), 7.46ꢀ7.53 (q, 4H, J
= 8.0 Hz, 7.6 Hz, ArꢀH of phenyl), 7.67ꢀ7.69 (d, 2H, J = 8.0 Hz, ArꢀH of 4ꢀchloro phenyl), 7.80ꢀ7.82 (d, 2H, J = 8.0 Hz, ArꢀH of 4ꢀchloro
phenyl), 7.93ꢀ7.97 (d, 1H, J = 16.0 Hz, CH=CH), 7.98 (s, 1H, ArꢀH of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 7.99ꢀ8.03 (d, 1H, J =
13
16.0 Hz, CH=CH), 8.50 (s, 1H, ArꢀH of pyrazole). C NMR: (400 MHz, CDCl3, δ ppm): 9.23 (CH3 of triazole), 14.34 (CH3 of 2,3ꢀdichloroꢀ5ꢀ
trifluoromethylꢀ6ꢀmethyl phenyl), 118.35, 119.40, 121.85, 126.66, 127.35, 128.75, 128.80, 129.63, 129.91, 130.00, 132.14, 132.21, 135.01,
135.23, 136.10, 139.42, 143.72, 154.31, 183.70 (C=O of Chalcone). MS: m/z = 615.4 (M+), 616.2 (M++1). Anal. calcd. for C29H19Cl3F3N5O:
Calculated: C(56.47%), H(3.10%), N(11.35%) ; Found C(56.51%), H(3.12%), N(11.37%).
4.3.15. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(1-(4-chloro phenyl)-3-(3-bromo
phenyl)-1H-pyrazol-4-yl) prop-2-en-1-one (6d)
1
IR (KBr) γ/cmꢀ1: 3067 (ArꢀH), 1663 (C=O), 1565 (C=N), 1163 (C–F) and 713 (C–Cl). HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.093 (d, 3H, J =
0.8 Hz, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 2.49 (s, 3H, CH3 of triazole), 7.356ꢀ7.393 (t, 1H, J = 7.6 Hz, 7.2 Hz, ArꢀH of 3ꢀ
bromo phenyl), 7.477ꢀ7.540 (q, 4H, J = 8.4, 7.6 Hz, ArꢀH of 4ꢀchloro phenyl), 7.683ꢀ7.704 (d, 2H, J = 8.4 Hz, ArꢀH of 4ꢀchloro phenyl and 3ꢀ
bromo phenyl), 7.801ꢀ7.822 (d, 2H, J = 8.4 Hz, ArꢀH of 3ꢀbromo phenyl and ArꢀH of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 7.995ꢀ
8.006 (d, 2H, J = 4.4 Hz, CH=CH), 8.523 (s, 1H, ArꢀH of pyrazole). 13C NMR: (400 MHz, CDCl3, δ ppm): 9.23 (CH3 of triazole), 14.34 (CH3 of
2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 118.35, 119.40, 121.85, 126.66, 127.35, 128.75, 128.80, 129.63, 129.91, 130.00, 132.14,
132.21, 135.01, 135.23, 136.10, 139.42, 143.72, 154.31, 183.70 (C=O of Chalcone). MS: m/z = 693.2 (M+), 694.2 (M++1). Anal. calcd. for
C29H18BrCl3F3N5O: Calculated: C(50.06%), H(2.61%), N(10.07%) ; Found C(50.10%), H(2.57%), N(10.11%).
4.3.15. (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(1-(phenyl)-3-(3-bromo phenyl)-
1H-pyrazol-4-yl) prop-2-en-1-one (6e)
1
IR (KBr) γ/cmꢀ1: 3066 (ArꢀH), 1668 (C=O), 1567 (C=N), 1164 (C–F) and 711 (C–Cl). HꢀNMR: (400 MHz, CDCl3, δ ppm): 2.092 (d, 3H, J =
0.8 Hz, CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 2.491 (s, 3H, CH3 of triazole), 7.348ꢀ7.388 (t, 1H, J = 7.6 Hz, 7.6 Hz, ArꢀH of
3ꢀbromo phenyl), 7.453ꢀ7.537 (m, 5H, ArꢀH of phenyl), 7.739ꢀ7.760 (dd, 1H, J = 5.2 Hz, 2.0 Hz, ArꢀH of 3ꢀbromo phenyl), 7.820ꢀ7.840 (d, 2H,
J = 8.0 Hz, ArꢀH of 3ꢀbromo phenyl), 7.960ꢀ8.001 (d, 1H, J = 16.4 Hz, CH=CH), 8.048ꢀ8.088 (d, 1H, 16 Hz, CH=CH), 8.287 (s, 1H, ArꢀH of
13
2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 8.53 (s, 1H, ArꢀH of pyrazole). C NMR: (400 MHz, CDCl3, δ ppm): 9.29 (CH3 of triazole),
14.24 (CH3 of 2,3ꢀdichloroꢀ5ꢀtrifluoromethylꢀ6ꢀmethyl phenyl), 118.35, 119.40, 121.85, 126.66, 127.35, 128.75, 128.80, 129.63, 129.91, 130.00,
132.14, 132.21, 135.01, 135.23, 136.10, 139.42, 143.72, 154.31, 184.10 (C=O of Chalcone). MS: m/z = 659.3 (M+), 660.3 (M++1). Anal. calcd.
for C29H19BrCl2F3N5O: Calculated: C(52.67%), H(2.90%), N(10.59%) ; Found C(52.65%), H(2.93%), N(10.62%).
10

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Acknowledgments
One of the authors, Manjunatha Bhat, is grateful to the management of SeQuent Scientific Ltd., New Mangalore, India for encouraging research
work. Manjunatha Bhat is also thankful to Late Prof. A. Srikrishna, Dept. of Organic Chemistry, IISc, Bangalore and MIT, Manipal for
1
providing H NMR and 13C NMR spectral facilities. We are also thankful to Dept. of Biochemistry, Jnanasahyadri, Kuvempu University,
Shankarghatta, Karnataka and Dept. of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka for providing sincere
help for the biological activity studies. Authors are also thankful to Chairman, Dept. of Chemistry, Mangalore University.
References and notes
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12

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Table 1: Characterization data of the compounds (5a-k) and (6a-e)
Comp.
Ar
Mol. formula
Mol.
Wt
M.P
(°C)
Yield
(%)
C, H, N Analysis (%)
Found (calculated)
C
H
N
Phenyl
C20H14Cl2F3N3O
C20H12Cl2F4N3O
C20H14Cl2F3N3O2
C22H18Cl2F3N3O
C20H13Cl2F4N3O
C20H13Cl3F3N3O
440.2 145ꢀ147 71
492.7 178ꢀ180 70
456.2 148ꢀ150 72
468.3 152ꢀ154 74
458.2 162ꢀ164 72
54.58
3.24
9.58
(9.54)
5a
5b
5c
5d
5e
(54.56) (3.21)
48.78 2.44
(48.76) (2.45)
52.62 3.08
(52.65) (3.09)
56.40 3.85
(56.42) (3.87)
52.42 2.88
(52.42) (2.86)
50.62 2.78
(50.60) (2.76)
53.56 3.47
(53.63) (3.43)
52.43 2.89
(52.42) (2.86)
50.64 2.79
(50.60) (2.76)
51.67 2.99
(51.72) (2.97)
51.90 3.35
(51.86) (3.32)
3ꢀClꢀ2Fꢀphenyl
4ꢀOHꢀphenyl
8.55
(8.53)
9.25
(9.21)
3,4,ꢀ(CH3)ꢀ
phenyl
8.92
(8.97)
4ꢀFꢀphenyl
9.19
(9.17)
474.7 167ꢀ169 70
470.3 168ꢀ170 74
458.2 169ꢀ171 71
8.82
(8.85)
8.98
(8.94)
9.19
5f
4ꢀClꢀphenyl
5g
5h
4ꢀOCH3ꢀ phenyl C21H16Cl2F3N3O2
2ꢀFꢀphenyl
2ꢀClꢀphenyl
3ꢀpyridyl
C20H13Cl2F4N3O
C20H13Cl3F3N3O
C19H13Cl2F3N4O
C21H16Cl2F3N3OS
(9.17)
8.83
(8.85)
5i
5j
5k
474.7 172ꢀ174 73
441.2 179ꢀ181 70
486.3 180ꢀ182 73
12.76
(12.70)
4ꢀSCH3ꢀ phenyl
8.70
(8.64)
Ar2
Ar1
Phenyl Phenyl C29H20Cl2F3N5O
582.4 214ꢀ216 71
616.8 226ꢀ228 73
59.75
(59.81) (3.46)
56.50 3.13
(56.47) (3.10)
3.43
12.06
(12.02)
6a
6b
4ꢀClꢀ
Phenyl C29H19Cl3F3N5O
11.32
(11.35)
phenyl
4ꢀClꢀ
phenyl
C29H19Cl3F3N5O
616.8 231ꢀ233 72
56.51
(56.47) (3.10)
3.12
11.37
(11.35)
6c
6d
6e
Phenyl
3ꢀBrꢀ
phenyl
4ꢀClꢀ
phenyl
C29H18BrCl3F3N5O 695.7 256ꢀ258 72
50.10 2.57
10.11
(10.07)
(50.06) (2.61)
52.65 2.93
(52.67) (2.90)
3ꢀBrꢀ
phenyl
Phenyl C29H19BrCl2F3N5O 661.3 237ꢀ239 73
10.62
(10.59)

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Table 2: Determination of antiꢀbacterial activity of the synthesized compounds (5a-k) and (6a-e)
Organic
compounds
Escherichia
coli
Staphylococcus
Aureus
Pseudomonas
Aeruginosa
Bacillus subtilis
1
0.5
1
0.5
1
0.5
1
0.5
Concn.in
mg/ml
ZOI in mm a
mm
00
mm
00
mm
00
mm
00
mm
mm
00
mm
00
mm
00
00
Control
24±0.2
12±0.3
15±0.2
16±0.2
19±0.3
17±0.3
15±0.1
14±0.3
18±0.4
19±0.4
19±0.2
18±0.4
15±0.4
17±0.1
14±0.4
18±0.2
14±0.3
18±0.1
09±0.4
11±0.2
12±0.3
15±0.4
14±0.1
13±0.2
11±0.2
14±0.3
15±0.3
16±0.1
15±0.3
12±0.3
15±0.2
12±0.3
14±0.3
13±0.4
21±0.2 17±0.2
12±0.3 11±0.4
11±0.3 08±0.2
13±0.3 10±0.2
17±0.1 14±0.4
11±0.2 06±0.3
13±0.2 11±0.3
12±0.3 10±0.2
16±0.3 13±0.2
16±0.3 14±0.2
15±0.5 13±0.3
15±0.3 13±0.2
14±0.3 11±0.2
16±0.2 13±0.3
13±0.5 10±0.3
16±0.2 13±0.3
17±0.1 14±0.2
19±0.2
09±0.1
12±0.2
14±0.2
16±0.3
15±0.1
15±0.3
12±0.3
15±0.2
15±0.2
16±0.4
14±0.2
10±0.2
17±0.3
13±0.4
16±0.3
13±0.3
17±0.2 21±0.4 18±0.3
07±0.3 13±0.2 10±0.3
09±0.3 15±0.2 12±0.3
10±0.4 13±0.3 09±0.3
13±0.6 16±0.5 14±0.2
13±0.2 14±0.2 11±0.2
13±0.4 11±0.3 09±0.1
10±0.2 15±0.3 12±0.2
13±0.2 15±0.2 13±0.3
13±0.2 15±0.2 13±0.3
14±0.2 15±0.3 13±0.5
12±0.2 16±0.2 14±0.3
07±0.2 12±0.2 10±0.3
13±0.3 15±0.2 13±0.2
11±0.2 13±0.3 11±0.5
14±0.2 15±0.3 13±0.2
10±0.2 16±0.3 14±0.2
Ciproflaxin
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
6a
6b
6c
6d
6e
a The experiment was performed in triplicate and the values are expressed as Mean ±SD

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Table 3: Minimum inhibitory concentration (MIC) of the synthesized compounds (5a-k)
and (6a-e)
Organic
Escherichia
Staphylococcus
Aureus
Pseudomonas
Aeruginosa
Bacillus subtilis
Compounds in Coli
µg/ml a
12.5
6.52
6.25
6.25
6.12
6.25
12.5
6.25
6.25
12.5
3.12
6.25
3.15
12.5
3.15
6.25
3.25
12.5
12.5
12.5
3.15
13.2
12.5
12.5
6.25
6.25
6.25
6.25
12.5
12.5
12.5
6.25
7.15
3.15
25
12.5
6.25
12.5
6.25
12.5
14.2
6.25
6.25
6.25
6.25
3.12
12.5
6.25
6.25
6.50
6.25
3.10
5a
12.5
12.5
12.5
6.25
6.25
12.5
12.5
6.25
3.13
12.5
25.0
3.15
12.5
12.5
12.5
3.12
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
6a
6b
6c
6d
6e
Ciproflaxin
a The experiment was performed in triplicate and the values are expressed as Mean.

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Table 4: Determination of antiꢀfungal activity of the synthesized compounds (5a-k) and (6a-e)
Organic
compound
Aspergillus Flavus
Chrysosporium
Keratinophilum
Candida
Albicans
1
Concn. in
mg/ml
1
0.5
1
0.5
0.5
ZOI in mm a
mm
00
mm
00
mm
00
mm
00
mm
00
mm
00
Control
14±0.3 12±0.4
06±0.2 04±0.3
11±0.3 08±0.2
08±0.2 05±0.3
08±0.3 07±0.2
11±0.2 09±0.3
12±0.3 08±0.2
07±0.3 05±0.2
11±0.4 09±0.3
12±0.2 09±0.3
12±0.3 09±0.6
09±0.3 08±0.2
08±0.2 06±0.3
11±0.3 09±0.2
11±0.1 08±0.4
12±0.4 09±0.2
09±0.3 07±0.4
17±0.4 15±0.5
07±0.2 06±0.2
14±0.2 11±0.3
08±0.1 04±0.1
10±0.2 07±0.3
13±0.4 11±0.2
14±0.3 11±0.4
12±0.1 10±0.3
14±0.3 11±0.2
15±0.3 13±0.3
15±0.4 13±0.4
13±0.2 11±0.3
11±0.3 09±0.2
13±0.2 11±0.2
14±0.2 11±0.3
15±0.2 13±0.3
10±0.2 07±0.4
22±0.2 20±0.3
08±0.2 05±0.2
16±0.1 14±0.1
12±0.3 07±0.3
11±0.1 07±0.1
16±0.4 14±0.3
15±0.2 13±0.4
12±0.4 10±0.2
16±0.3 14±0.2
18±0.3 15±0.1
18±0.2 15±0.2
16±0.1 14±0.1
11±0.3 08±0.2
16±0.2 14±0.2
16±0.3 14±0.4
18±0.3 15±0.3
11±0.2 07±0.3
Fluconazole
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
6a
6b
6c
6d
6e
a The experiment was performed in triplicate and the values are expressed as Mean ±SD

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Table 5: MIC and MFC of the synthesized compounds (5a-k) and (6a-e)
Organic
Aspergillus Flavus
Chrysosporium
Keratinophilum
Candida Albicans
Compounds
in µg/ml a
MIC
MFC
MIC
MFC
MIC
MFC
15.5
50.5
16.3
62.5
10.5
50
5a
8.52
19.5
20.4
8.73
8.42
22.5
8.44
7.8
18.5
70.5
74.5
18.8
18.4
95.5
18.3
16.2
16.8
18.9
98
8.7
18.9
80.5
85.5
18.9
19.2
95.5
19.2
16.8
17.9
19.8
95.5
19.9
19.8
16.6
100
7.5
12.5
75
5b
20.8
22.8
8.9
13.5
14.8
7.8
5c
80
5d
12.7
12.8
85
5e
8.76
23.9
8.72
8.25
8.49
8.95
23.9
9.15
8.85
8.15
25.8
6.18
7.95
15.6
7.85
5.25
4.95
7.65
15.6
6.95
6.85
5.35
15.8
3.12
5f
5g
12.7
7.55
7.38
12.5
85
5h
5i
7.9
5j
8.68
22.8
8.35
8.7
5k
6a
19.2
18.8
16.1
100
12.2
11.8
7.75
100
6.18
6b
6c
7.7
6d
23.8
6.25
6e
12.5
12.7
Flucanazole
a The experiment was performed in triplicate and the values are expressed as Mean and
values were expressed as µg/ml.

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Table 6: Antioxidant activity of the synthesized compounds (5a-k) and (6a-e) by DPPH
method.
Concentration 15.62 ꢀ
62.5 µg/ml
IC50 ± SD (µg/ml)
% Inhibition
DPPH Method a
Compound
ABTS Method b
% Inhibition a
37.30 ꢀ 87.12
16.36 ± 1.633
78.5
5a
8.92 ꢀ 71.42
2.57 ꢀ 58.2
50.21 ± 1.241
255.13 ± 3.697
15.33± 1.727
67.87 ± 1.357
43.76 ± 1.898
15.38 ± 1.635
45.53 ± 1.629
62.9 ± 1.286
17.48± 1.627
16.99± 1.584
14.48 ± 1.629
34.91 ± 1.629
45.48 ± 1.432
62.94 ± 1.267
39.82 ± 1.425
35.6
15.8
80.4
25.3
53.1
81.2
58.6
43.2
76.9
77.8
81.8
63.5
59.7
43.3
58.6
5b
5c
5d
5e
5f
38.81 ꢀ 90.83
3.81 ꢀ 76.12
2.7 ꢀ 81.07
39.33 ꢀ 89.24
21.7 ꢀ 73.08
3.4 ꢀ 80.12
5g
5h
5i
34.61 ꢀ 85.89
35.67 ꢀ 83.63
42.7 ꢀ 91.18
32.9 ꢀ 78.82
6.81 ꢀ 71.55
4.87 ꢀ 70.22
28.9 ꢀ 72.23
5j
5k
6a
6b
6c
6d
6e
44.95 ꢀ 95.5
_
12.7 ± 0.68
_
88.5
_
Ascorbic acid
Blank
a Data presented is the Mean ± SD value of three independent determinations.
b Data presented is the mean value of three independent determinations.

Page 19 of 23
RSC Advances
View Article Online
DOI: 10.1039/C6RA22705H
Table 7: The inꢀvitro cytotoxic activity of (5a-k) and (6a-e) on cancer cells by MTT assay at
48h. of exposure.
Compound
IC50a in µM
MCFꢀ7
>100
MDAꢀMBꢀ231
>100
VERO
>100
MCFꢀ10A
>100
5a
10.3±0.4
>100
3.2±0.3
74.8±0.2
25.6±0.2
6.4±0.4
3.1±0.1
10.4±0.2
74.8±0.5
78.3±0.4
91.5±0.2
>100
20.9±0.3
>100
23.5±0.3
>100
5b
5c
>100
>100
>100
5d
7.8±0.3
8.3±0.2
16.3±0.4
67.6±0.3
69.9±0.4
>100
>100
>100
5e
>100
>100
5f
25.3±0.2
>100
26.7±0.2
>100
5g
5h
>100
>100
5i
>100
>100
5j
21.3±0.2
>100
>100
>100
5k
>100
>100
>100
6a
57.9±0.4
8.7±0.2
7.9±0.1
30.5±0.4
0.9 ± 0.2
54.8±0.4
3.2±0.2
3.4±0.1
48.3±0.4
1.1 ± 0.1
>100
>100
6b
>100
>100
6c
>100
>100
6d
>100
36.6±0.2
6e
Doxorubicinb
>100
>100
a Data presented is the Mean ± SD value of three independent determinations.
b Positive control.

RSC Advances
Page 20 of 23
O
N
N
H2N
N
H2N
O
H
O
S
Cl
O
N
Cl
N
O
COOH
N
N
Cl
CAI (Carboxyamido triazole
)
Tazobactam
(Anti-biotic)
(Anti-cancer)
OH
OH
View Article Online
DOI: 10.1039/C6RA22705H
HO
O
O
O
O
OH
Licochalcone A
(Anti-microbial)
Cardamonin
(Anti-cancer)
Figure 1: Examples of biologically active 1,2,3-Triazole and Chalcone pharmacopores.

Page 21 of 23
RSC Advances
OHC
N
N
N
F3C
O
O
N
N
O
N
R3
O
N
N
R2
Anti-microbial
Anti-oxidant
O
B
Anti-cancer
R1
R1=R2=H,Cl
O
A
Ar
N
N
Ar2
N
N
F3C
View Article Online
DOI: 10.1039/C6RA22705H
O
N
Ar1
N
N
Cl
F3C
N
Cl
O
(5a-k)
Cl
Targeted molecules (5a-k) and (6a-e)
(6a-e)
Cl
Figure 2: Representative examples A and B of anticancer, antimicrobial and anti-oxidant active heterocyclic molecules possessing 1,2,3-
triazole, chalcone and pyrazole moieties and targeted molecules (5a-k) and (6a-e).

RSC Advances
Page 22 of 23
CH3
CH3
CH3
F3C
NO2
Cl
F3C
F3C
NH2
Cl
N3
A
B
Cl
Cl
Cl
Cl
(3)
C
(1)
(2)
Ar1
Ar2COCH3
+
N
a
Ar2
Ar1
N
N
NH
b
Ar2
Ar1NHNH 2
N
O
CH3
N
CH3
iii(a-e)
OHC
i(a-e)
ii(a-e)
F3C
N
CH3
CH3
Cl
(4)
Cl
E
D
O
N
O
N
N
Ar2
Ar
H3C
View Article Online
N
N
H3C
CH3
N
DOI:F103.1C039/C6RA22705H
N
CH3
Cl
N
F3C
Cl
Ar1
Cl
(5a-k)
Cl
(6a-e)
Compd
.
5a
5b
5c
5d
3,4-
5e
4-F-
5f
5g
5h
5i
5j
5k
phenyl 3-Cl-2- 4-OH-
4-Cl- 4-OCH3- 2-F-
2-Cl-
pyridyl 4-SCH3-
phenyl
Ar
F-
phenyl
phenyl (CH3)2-
phenyl
phenyl phenyl phenyl
phenyl phenyl
Compound
Ar2
6a
phenyl
6b
6c
6d
6e
4-Cl-phenyl phenyl
3-Br- phenyl 3-Br- phenyl
Ar1
phenyl
phenyl
4-Cl-phenyl
4-Cl-phenyl
phenyl
A. Zn/ HCl/ Methanol B. NaNO2/ HCl/ 0-5°C and NaN3/ H2O/ 0-5°C C. NaOCH3/ Acetyl acetone/ Methanol/ 50°C D. ArCHO/ NaOH/
Ethanol/ 30°C E. iii(a-e)/ NaOH/ Ethanol. (Claisen-Schimidt reaction).
a. AcOH/ NaOH/ 30°C b. DMF/ POCl3/ 70-75°C (Vilsmeier-Haack reagent).
Scheme 1: Synthetic scheme for the compounds (5a-k) and (6a-e)

Page 23 of 23
RSC Advances
Graphical Abstract
A new series of 1,2,3-Triazolyl chalcone derivatives (5a-k) and (6a-e) were synthesized via a Claisen-Schimidt reaction and evaluated for their
preliminary anti-microbial, anti-oxidant and anti-cancer activities. Some of the derivatives shown excellent activities against the respective
standards.
Ar
N
N
F3C
N
O
Cl
Cl
5 (a-k)
F3C
NO2
Cl
N
Ar1
Ar2
N
View Article Online
DOI: 10.1039/C6RA22705H
Cl
N
N
(1)
F3C
N
O
Cl
Cl
6 (a-e)