Synthesis of novel substituted 4,6-dimethoxy-N-phenyl-1,3,5-triazin-2-amine derivatives and their antibacterial and antifungal activities

Article abstract of DOI:10.14233/ajchem.2015.19114

An efficient and convenient method of synthesis of 2-chloro-4,6-dimethoxy-1,3,5-triazine from cyanuric chloride in a short reaction time followed by synthesis of biological active novel substituted 4,6-dimethoxy-N-phenyl-1,3,5-triazin-2-amine (4a-x) using substituted anilines and heterocyclic amines, anhydrous K2CO3 in dry THF as solvent has been developed. Advantages of this methodology are short reaction time, excellent yield of products, easy work-up procedure. The synthesized compounds were confirmed by FT-IR, 1H NMR, mass spectral data. All the synthesized derivatives (4a-x) were screened for their antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa species and antifungal activities against Candida albicans MTCC 227, Candida glabrata NCIM 3236, Candida tropicalis NCIM 3110 and Aspergillus Niger NCIM 545 species.

Full text of DOI:10.14233/ajchem.2015.19114

Asian Journal of Chemistry; Vol. 27, No. 11 (2015), 4130-4134
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.19114
Synthesis of Novel Substituted 4,6-Dimethoxy-N-phenyl-1,3,5-triazin-2-amine
Derivatives and Their Antibacterial and Antifungal Activities
*
RAVINDRA S. SHINDE and SHRIDHAR D. SALUNKE
Research Center in Chemistry, Rajarshi Shahu Mahavidyalaya, Latur-413 512, India
*Corresponding author: E-mail: salunke_shridhar@yahoo.co.in; rss.333@rediffmail.com
Received: 18 February 2015;
Accepted: 31 March 2015;
Published online: 16 July 2015;
AJC-17418
An efficient and convenient method of synthesis of 2-chloro-4,6-dimethoxy-1,3,5-triazine from cyanuric chloride in a short reaction time
followed by synthesis of biological active novel substituted 4,6-dimethoxy-N-phenyl-1,3,5-triazin-2-amine (4a-x) using substituted anilines
and heterocyclic amines, anhydrous K2CO3 in dry THF as solvent has been developed. Advantages of this methodology are short reaction
time, excellent yield of products, easy work-up procedure. The synthesized compounds were confirmed by FT-IR, 1H NMR, mass spectral
data. All the synthesized derivatives (4a-x) were screened for their antibacterial activity against Staphylococcus aureus, Bacillus subtilis,
Escherichia coli, Pseudomonas aeruginosa species and antifungal activities against Candida albicans MTCC 227, Candida glabrata
NCIM 3236, Candida tropicalis NCIM 3110 and Aspergillus niger NCIM 545 species.
Keywords: Antimicrobial Activity, Cyanuric chloride, Substituted 1,3,5-triazin-2-amine.
INTRODUCTION
EXPERIMENTAL
1,3,5-Triazines (s-triazine) is an important class of hetero-
cyclic compounds found in various natural products with a
broad range of biological activities, such as antimycobacterial
agents1, focal adhesion kinase (FAK) inhibitors with anti-
angiogenic activity on HUVEC cells2, HIV-1 non-nucleoside
reverse transcriptase inhibitors adenosine receptor3, antiamoebic4,
cathepsin B inhibitor5, adenosine receptor antagonist6, antiviral7,
anticancer8, antimicrobial9, antileishmanial10, carbonic anhy-
drase inhibitor11 and antimalarial12.
The reagent grade chemicals were obtained from commercial
sources and purified by either distillation or recrystallization
before use. The purity of synthesized compounds has been
checked by thin layer chromatography. Melting points were
determined by open capillary method and are uncorrected. IR
spectra are recorded on FT-IR Bruker with KBr disc. 1H NMR
spectra are recorded in DMSO-d6 on a Bruker DRX-400 MHz
using TMS as internal standard. The chemical shift is reported
as parts per million (ppm) and mass spectra were determined
on Jeol-SX-102 (FAB) spectrometer.
Synthesis of 2-chloro-4,6-dimethoxy-1,3,5-triazine (2):
To 57 mL of methanol and 5 mL of water 16.8 g (0.2 mol) of
sodium bicarbonate and 18.5 g (0.1 mol) of cyanuric chloride
(1) were added. The temperature of reaction mixture increased
to 35 °C. The reaction mixture was further refluxed for 0.5 h
until CO2 was completely removed. Then the contents were
poured onto ice cold water and filtered. The white solid product
(2) obtained was dried in desiccators (Scheme-I). m.p. 74-76 °C,
1H NMR (400 MHz, DSMO-d6) δ ppm: 4.05 (s, 6H).
Recently, s-triazine attracted many researchers as its symme-
trical structure facilitates to synthesize diverse set of analogue
and provides the basis for designing biological relevant mole-
cules with wide spread applications such as the therapeutics13-19
.
Some derivative of cyanuric chloride (CC), especially dimethoxy
analogue is important starting compound used for synthesis
of substituted 4,6-dimethoxy-N-phenyl-1,3,5-triazin-2-amine
derivatives.
In this article, 2-chloro-4,6-dimethoxy-1,3,5-triazine
(CDMT) was prepared by using cyanuric chloride, methanol
and catalytic amount of sodium bicarbonate followed by
synthesis of novel substituted 4,6-dimethoxy-N-phenyl-1,3,5-
triazin-2-amines (4a-x) by using CDMT, substituted anilines/
heterocyclic amines and anhydrous K2CO3 in dry THF. All the
synthesized compounds were screened against antimicrobial
activity.
Cl
Cl
NaHCO3
N
N
+
CH3-OH
N
N
Stirr
30 min
Cl
N
1
Cl
O
N
O
2
Scheme-I: Synthesis of 2-chloro-4,6-dimethoxy-1,3,5-triazine

Vol. 27, No. 11 (2015)
Synthesis of Novel Substituted 4,6-Dimethoxy-N-phenyl-1,3,5-triazin-2-amine Derivatives 4131
TABLE-1
Possible mechanism of 2-chloro-4,6-dimethoxy-1,3,5-
triazine: Methanol (2 mol) reacts with sodium bicarbonate (2
mol) to form methoxy anion as nucleophile (step-I). Then two
chlorine atoms of cyanuric chloride (1) are substituted by
methoxy anion with the formation of 2-chloro-4,6-dimethoxy-
1,3,5-triazine (2) (step-II).
YIELD AND MELTING POINTS OF SUBSTITUTED
4,6-DIMETHOXY-N-PHENYL-1,3,5-TRIAZIN-
2-AMINE DERIVATIVES
Yield m.p.
Compd.
Reactants (3)
Products (4)
(%)
(°C)
O
NH2
O
N
O
O
Step-I: Formation of nucleophile
N
126-
128
4a
75
NH
N
O
O
2 NaHCO3
H C ONa + 2 H2O + CO
+
2
2H3C OH
2
3
2
Nucleophile
O
O
NH2
Step-II: Syntheis of 2-chloro-4,6-dimethoxy-1,3,5-triazine
O
N
N
120-
122
4b
4c
4d
4e
4f
73
72
73
70
70
O
N
O
NH
Cl
O
Stir
O
N
N
N
N
+
2
O CH3
Heat
30 min
Cl
N
Cl
Cl
N
O
F
N
2
NH2
O
N
182-
184
N
O
NH
General procedure for the synthesis of substituted 4,6-
N
F
N
dimethoxy-N-phenyl-1,3,5-triazin-2-amines (4a-x): 2-Chloro-
4,6-dimethoxy-1,3,5-triazine (1 mmol) (2), substituted aniline
(1 mmol)/heterocyclic amines (3) (1 mmol), anhydrous K2CO3
(2 mmol) were added in dry THF (5 mL) taken in a round-
bottom flask. The reaction mixture was refluxed at 70 °C for
4 h. After completion of the reaction the product is confirmed
on thin-layer chromatography (TLC) using eluent (2:8 mL,
ethyl acetate-hexane). The reaction mixture was quenched with
water and the crude product was extracted with ethyl acetate
(3 times) and organic layer was separated and dried over
anhydrous Na2SO4.The solvent evaporated on rotavapour. The
Crude material was purified by column chromatography (ethyl
acetate-n-hexane) and product 4(a-x) with good yield (70-
75 %) were obtained (Scheme-II). Yield and melting points
of synthesized 4,6-dimethoxy-N-phenyl-1,3,5-triazin-2-amine
derivatives are given in Table-1.
O
NH2
O
N
N
N
108-
110
NH
O
O
F3CO
NH2
O
N
N
N
125-
126
NH
OCF3
O
F
F
NH2
O
N
N
N
168-
170
NH
F
F
O
R1
F
NH2
O
N
Cl
NH2
N
N
142-
144
K2CO3
NH
4g
4h
72
73
NH
N
N
+
F
O
THF/70 °C
3.30-4 h
N
N
R1
O
N
O
O
N
3
O
2
O
N
O
N
N
110-
111
4(a-x)
NH
NH2
O
Scheme-II: Synthesis of substituted 4,6-dimethoxy-N-phenyl-1,3,5-triazin-
2-amines from substituted anilines and 2-chloro-4,6-dimethoxy-
1,3,5-triazine
O
F
NH2
O
N
N
N
163-
194
Spectral data
4i
4j
72
72
NH
4,6-Dimethoxy-N-(3,5-dimethoxyphenyl)-1,3,5-triazin-
2-amine (4a): m.f.: C13H16N4O4, Off-white solid; FTIR (KBr,
F
O
ν
max, cm-1): 3338 (N-H str. of sec-amine), 2836 (C-H), 1629
O
(Ar-C=C), 1207 (C-O); 809 (C-N, s-triazine). 1H NMR (400
MHz, DSMO-d6): δ ppm: 3.72 (s, 6H), 3.77 (s, 6H), 6.21 (s,
1H), 7.05 (s, 2H), 10.06 (s, 1H), MS(ESI): m/z 292.40 (M+1).
4,6-Dimethoxy-N-(3,4-dimethoxyphenyl)-1,3,5-triazin-
2-amine (4b): m.f.: C13H16N4O4, Off-white solid; FTIR (KBr,
N
O
N
O
H2N
210-
212
N
N
NH
O
N

4132 Shinde et al.
Asian J. Chem.
F
O
N
O
N
NH2
N
N
O
O
N
O
NH
4k
73 88-90
116-
118
N
N
NH2
4u
4v
70
N
NH
O
F
H
N
H
N
N
O
N
O
O
N
O
150-
N
N
4l
72
N
N
131-
132
152
N
NH
H2N
72
NH
H2N
O
O
O
O
N
O
N
H2N
O
N
N
N
206-
208
H
4m
72
N
O
N
4w
4x
70
70
94-96
NH
H2N
O
N
N
F
O
N
O
O
N
NH2
N
N
N
N
H
NH2
116-
118
F
138-
140
NH
4n
73
N
O
N
N
F
N
NH2
N
O
N
ν
max, cm-1): 3335 (N-H str. of sec-amine), 2939 (C-H), 1614
N
N
180-
182
(Ar-C=C), 1226 (C-O); 813 (C-N, s-triazine). 1H NMR (400
MHz, DSMO-d6) δ ppm: 3.71 (s, 3H), 3.74 (s, 3H), 3.91 (s,
6H), 6.90 (dd, J = 12 Hz, 1H), 7.14 (dd, J = 12 Hz, 1H), 7.52
(s, 1H), 9.95 (s, 1H), MS(ESI): m/z292 (M+1).
4o
4p
72
NH
F
O
N
N-(6-Fluoropyridin-3-yl)-4,6-dimethoxy-1,3,5-triazin-
2-amine (4c): m.f.: C10H10N5O2F, Off-white solid; FTIR (KBr,
O
NH2
N
N
148-
150
73
max, cm-1): 3337 (N-H str. of sec-amine), 2953 (C-H), 1628
N
O
NH
ν
(Ar-C=C), 1202 (C-O); 809 (C-N, s-triazine). 1H NMR (400
MHz, DSMO-d6) δ ppm: 3.91 (s, 6H), 7.19 (dd, J = 8 Hz,
1H), 8.27 (dd, J = 8 Hz, 1H), 8.50 (s, 1H), 10.34 (s, 1H), MS
(ESI): m/z 251 (M+1).
N
F
NH2
F
O
N
O
4,6-Dimethoxy-N-(3-methoxyphenyl)-1,3,5-triazin-2-
amine (4d): m.f.: C12H14N4O3, Off-white solid; FTIR (KBr,
194-
196
N
4q
4r
4s
4t
70
NH
Cl
ν
max, cm-1): 3280 (N-H str. of sec-amine), 2983 (C-H), 1618
N
F
F
(Ar-C=C), 1199 (C-O); 813 (C-N, s-triazine). 1H NMR (400
MHz, DSMO-d6) δ ppm: 3.74 (s, 3H), 3.91 (s, 6H), 6.62 (d,
1H), 7.24 (d,H), 7.50-7.51 (s, 1H), 10.36 (s, 1H), MS (ESI):
m/z 262 (M+1).
Cl
H2N
Cl
O
120-
122
N
70
4,6-Dimethoxy-N-(3-(trifluoromethoxyphenyl)-1,3,5-
triazin amine (4e): m.f.: C12H11N4O3F3, Off-white solid; FTIR
(KBr, νmax, cm-1): 3297 (N-H str. of sec-amine), 2950 (C-H),
1618 (Ar-C=C), 1225 (C-O); 804 (C-N, s-triazine). 1H NMR
(400 MHz, DSMO-d6) δ ppm: 3.93 (s, 6H), 6.97 (d, J = 8 Hz,
1H), 7.41 (t, J = 8 Hz, 1H), 7.63 (d, J = 8 Hz, 1H), 7.96 (s,
1H), 10.36 (s, 1H), MS (ESI): m/z 316 (M+1).
Cl
N
O
NH
N
CF3
O
H2N
122-
124
N
70
N
O
NH
CF3
N-(3,4-Difluorophenyl)-4,6-dimethoxy-1,3,5-triazin-2-
amine (4f): m.f.: C11H10N4O2F2, Off-white solid; FTIR (KBr,
N
ν
max, cm-1): 3145 (N-H str. of sec-amine), 2945 (C-H), 1637
(Ar-C=C), 1214 (C-O); 810 (C-N, s-triazine). 1H NMR (400
MHz, DSMO-d6) δ ppm: 3.93 (s, 6H), 7.27-7.34 (m, 1H), 7.43-
7.47 (m, 1H), 7.89 (s, 1H), 10.25 (s, 1H), MS (ESI): m/z 268
(M+1).
F
SO2CH3
O
N
O
F
SO2CH3
108-
110
N
N
70
NH
H2N
N-(4-Fluorophenyl)-4,6-dimethoxy-1,3,5-triazin-2-
amine (4g): m.f.: C11H11N4O2F, Off-white solid; FTIR (KBr,

Vol. 27, No. 11 (2015)
Synthesis of Novel Substituted 4,6-Dimethoxy-N-phenyl-1,3,5-triazin-2-amine Derivatives 4133
ν
max, cm-1): 3185 (N-H str. of sec-amine), 2955 (C-H), 1640
antibacterial activity and potato dextrose agar and yeast peptone
dextrose agar were used as the culture media for antifungal
activity. The commercial available chloramphenicol and grise-
ofulvin in DMSO served as reference drugs for antibacterial
and antifungal activity respectively to compare inhibition of
growth. Both the plate containing bacterial organism and fungal
organism were incubated at 37 °C for 48 h. Averages of three
independent determinations were recorded.Agars were melted
and poured in Petri dishes according to Clinical and Laboratory
Standards Institute (CLSI, M2-A5 January 2007). Approxi-
mately 107 cells cultures were spread and cups were prepared
by sterile borer. 100 µL compounds were inoculated in each
cup. The plates were incubated at 37 °C, examined after 24 h
and incubated further for 48 h, where necessary. The zone of
inhibition produced by each compound was measured in mm.
(Ar-C=C), 1210 (C-O); 812 (C-N, s-triazine). 1H NMR (400
MHz, DSMO-d6) δ ppm: 3.91 (s, 6H), 7.09 (dd, J = 4 Hz,
2H), 7.71 (dd, J = 4 Hz, 2H), 10.07 (s, 1H), MS (ESI): m/z
250 (M+1).
N-(Tetrahydro-2H-pyran-2-yl)-4,6-dimethoxy-1,3,5-
triazin-2-amine (4h): m.f.: C10H16N4O3, Off-white solid; FTIR
(KBr, νmax, cm-1): 3255 (N-H str. of sec-amine), 2945 (C-H),
1610 (Ar-C=C), 1205 (C-O); 807 (C-N, s-triazine).1H NMR
(400 MHz, DSMO-d6) δ ppm: 1.51-1.58 (m, 2H), 1.77-1.81
(m, 2H), 3.37 (q, 2H), 3.83 (s, 3H), 3.84 (s, 3H), 3,96 (t, 2H),
4.01 (t, 1H), 7.85 (s, 1H), MS (ESI): m/z 240 (M+1).
Biological evaluation
Antibacterial and antifungal activity: The compounds
were diluted in dimethyl sulfoxide (DMSO) with 1 mg/mL
concentrations for bioassay. The antimicrobial activity was
evaluated by antimicrobial assay of the compounds by standard
method i.e. agar cup plate method against a panel of human
pathogenic micro organisms: Gram-positive, Staphylococcus
aureus NCIM 2178, B. subtilis NCIM 2250, Gram-negative,
Escherichia coli NCIM 2137 and Pseudomonas aeruginosa
NCIM 2036, while for the antifungal assay studies, Candida
albicans MTCC 227, Candida glabrata NCIM 3236, Candida
tropicalis NCIM 3110 and Aspergillus niger NCIM 545 fungi
were used. Nutrient agar was used as the culture media for
RESULTS AND DISCUSSION
2-Chloro-4,6-dimethoxy-1,3,5-triazine is characterized by
1H NMR spectra which is confirmed by chemical shift value
at δ 4.04 (6H, s) and mass spectra with m/z 175.5. The structure
of 4,6-dimethoxy N-phenyl-1,3,5-tirazine amines/heterocyclic
amines were confirmed by IR, 1H NMR, Mass spectra. The IR
spectra of compound 4(a-x) shows the characteristic absorption
band at ν 3225-3330 cm-1 (-NH- sec-amine), 3000-2950 cm-1
(-CH stretching in aliphatic), 1450-1650 cm-1, (-C=C, -C-H
aromatic stretching), 1199-1225 cm-1 (C-O stretching in
TABLE-2
ANTIBACTERIAL AND ANTIFUNGAL ACTIVITIES OF SUBSTITUTED
4,6-DIMETHOXY-N-PHENYL-1,3,5-TRIAZIN-2-AMINE DERIVATIVES 4(a-x)
Gram positive bacteria
Gram negative bacteria
Compound
C. albicans
C. tropicalis
C. glabrata
A. niger
S. aureus
16
B. subtilis
15
E. coli
11
11
19
15
21
20
18
15
19
13
12
20
15
13
20
18
18
17
22
21
19
14
15
19
P. aeruginosa
15
13
18
14
21
19
17
14
18
14
13
21
13
11
19
15
19
16
21
22
21
13
13
18
14
14
19
14
24
23
19
14
18
16
16
21
15
15
19
15
19
18
23
22
19
16
15
18
15
14
18
16
23
22
17
15
17
15
15
20
14
12
18
12
18
20
22
21
18
15
12
17
12
13
17
11
21
20
16
17
16
12
11
19
11
13
17
11
17
12
18
19
16
13
16
16
14
13
16
15
22
21
17
15
17
13
13
18
13
15
16
13
16
18
19
18
17
15
13
15
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
16
13
20
20
16
16
25
24
23
22
19
18
16
17
20
21
16
15
16
15
22
21
16
18
15
14
20
19
16
16
20
19
16
18
23
23
4t
23
24
4u
4v
4w
4x
20
22
16
15
16
18
20
21
Chloramphenicol
(250 µg/mL)
24
25
20
22
–
–
–
–
Griseofulvin
DMSO
–
00
–
00
–
00
–
00
23
00
24
00
22
00
21
00
Zone of inhibition (mm)

4134 Shinde et al.
Asian J. Chem.
aromatic compound), 802-821 cm-1 (C3 N3 in s-triazine ring).
The chemical shift value of compounds 4(a-x) is recorded on
1H NMR instrument at frequency 400 MHz by using solvent
DSMO-d6. The compounds are characterized by peak observed
for aromatic/heterocyclic sec-amine (-NH-) at 9.95-10.34
δ ppm (s, 1H). All the synthesized derivatives (4a-x) were
screened for their anti-bacterial and antifungal activities.
Compounds 4c, 4e, 4f, 4g, 4i, 4l, 4o, 4q, 4s, 4t, 4u, 4x are
found antibacterial against human pathogenic micro organisms
(Table-2).Also compounds 4c, 4e, 4f, 4g, 4i, 4l, 4o, 4q, 4r, 4s,
4t, 4u and 4x are found potential antifungal against Candida
albicans MTCC 227, Candida glabrata NCIM 3236, Candida
tropicalis NCIM 3110 and Aspergillus niger NCIM 545 (Table-2).
REFERENCES
1. V.R. Avupati, R.P. Yejella, V.R. Parala, K.N. Killari, V.M.R. Papasani,
P. Cheepurupalli, V.R. Gavalapu and B. Boddeda, Bioorg. Med. Chem.
Lett., 23, 5968 (2013).
2. P. Dao, R. Jarray, J. Le Coq, D. Lietha, A. Loukaci, Y. Lepelletier, R.
Hadj-Slimane, C. Garbay, F. Raynaud and H. Chen, Bioorg. Med. Chem.
Lett., 23, 4552 (2013).
3. X. Chen, P. Zhan, C. Pannecouque, J. Balzarini, E. De Clercq and X.
Liu, Eur. J. Med. Chem., 51, 60 (2012).
4. M.Y. Wani, A.R. Bhat, A. Azam, I. Choi and F. Athar, Eur. J. Med.
Chem., 48, 313 (2012).
5. I. Sosiè, B. Mirkoviæ, S. Turk, B. Štefane, J. Kos and S. Gobec, Eur. J.
Med. Chem., 46, 4648 (2011).
6. G. Pastorin, S. Federico, S. Paoletta, M. Corradino, F. Cateni, B.
Cacciari, K. Klotz, Z. Gao, K.A. Jacobson, G. Spalluto and S. Moro,
Bioorg. Med. Chem., 18, 2524 (2010).
Conclusion
7. M. Krecmerova, M. Masojidkova and A. Holy, Bioorg. Med. Chem.,
18, 387 (2010).
The present methodology for synthesis of 2-chloro-
4,6-dimethoxy-1,3,5-triazine from cyanuric chloride has an
added advantage of short reaction time of 0.5 h giving an
excellent yield of 75 %. Further synthesis of substituted 4,6-
dimethoxy-N-phenyl-1,3,5-triazin-2-amines (4a-x) using
2-chloro-4,6-dimethoxy-1,3,5-triazine and substituted anilines/
heterocyclic amines (1 mmol) in dry THF offer uniqueness in
synthesis in presence of anhydrous K2CO3 at moderate tempe-
rature (70 °C) condition, shorter reaction time, good yield (70-
75 %) of product. The synthesized products (4a-x) showed
promising antibacterial activity (zone of inhibition: 11 mm to
25 mm) and antifungal activity (zone of inhibition: 11 mm to
24 mm).
8. F. Popowycz, C. Schneider, S. DeBonis, D.A. Skoufias, F. Kozielski,
C.M. Galmarini and B. Joseph, Bioorg. Med. Chem., 17, 3471 (2009).
9. C. Zhou, J. Min, Z. Liu, A. Young, H. Deshazer, T. Gao, Y.T. Chang
and N.R. Kallenbach, Bioorg. Med. Chem. Lett., 18, 1308 (2008).
10. N. Sunduru, A. Agarwal, S.B. Katiyar, Nishi, N. Goyal, S. Gupta and
P.M.S. Chauhan, Bioorg. Med. Chem., 14, 7706 (2006).
11. V. Garaj, L. Puccetti, G. Fasolis, J.-Y. Winum, J.-L. Montero, A.
Scozzafava, D. Vullo, A. Innocenti and C.T. Supuran, Bioorg. Med.
Chem. Lett., 15, 3102 (2005).
12. T. Vilaivan, N. Saesaengseerung, D. Jarprung, S. Kamchonwongpaisan,
W. Sirawaraporn andY.Yuthavong, Bioorg. Med. Chem., 11, 217 (2003).
13. M. Kitamura, F. Kawasaki, K. Ogawa, S. Nakanishi, H. Tanaka, K.
Yamada and M. Kunishima, J. Org. Chem., 79, 3709 (2014).
14. A.B. Patel, K.H. Chikhalia and P. Kumari, Eur. J. Med. Chem., 79, 57
(2014).
15. R.V. Patel, P. Kumari, D.P. Rajani and K.H. Chikhalia, Eur. J. Med.
Chem., 46, 4354 (2011).
16. B. Akhlaghinia and E.A. Roohi, Lett. Org. Chem., 2, 725 (2005).
17. K. Bretterbauer and C. Schwarzinger, Curr. Org. Synth., 9, 342 (2012).
18. G. Giacomelli, A. Porcheddu and L. De Luca, Curr. Org. Chem., 8, 1497
(2013).
ACKNOWLEDGEMENTS
The authors are thankful to Dr. V.S. Shembekar, Director,
Department of Biotechnology, Rajarshi Shahu Mahavidyalaya,
Latur for providing the facility to carry out the biological
screenings. Thanks are also due to S.A.I.F. Division, Punjab
University, Chandigarh for NMR and mass spectroscopic
analysis.
19. X. Qin, W. Lu,Y. Luo, G. Chang, A.M. Asiri, A.O. Al-Youbi and X. Sun,
Curr. Nanosci., 8, 393 (2012).