Synthesis and in vitro antimicrobial activity of some triazole derivatives

Article abstract of DOI:10.4067/S0717-97072010000300019

Some 4-[{l-(substituted)methylidine}-amino]-3-(4-pyridyl)-5-mercapto-4H-l, 2,4-triazol (3a- 3f) and N-[5-(4-substituted)-lH-l,2,3-triazol-l-yl] isonicotinamide derivatives (5a- 5e) were synthesized by a sequence of reactions starting from isonicotinic acid hydrazide and is illustrated in scheme l and 2. The antibacterial and antifungal activities of newly synthesized compounds were tested by the disc diffusion method using nutrient agar medium against various microorganisms such as gram positive Staphylococcus aureus and Bacillus subtilis, gram negative Escherichia coli and the fungi Aspergillus niger and Candida albicans. Ciprofloxacin and Fluconazole at 50 μg/mL were used as standard drugs for antibacterial and antifungal activities, respectively. All the synthesized compounds showed significant activity against various microorganisms.

Full text of DOI:10.4067/S0717-97072010000300019

J. Chil. Chem. Soc., 55, Nº 3 (2010)
SYNTHESIS AND In vitro ANTIMICROBIAL ACTIVITY OF SOME TRIAZOLE DERIVATIVES
RAVINESH MISHRA*, RAJIV KUMAR, SURESH KUMAR, JASEELA MAJEED,
MOHD RASHID, SAMEER SHARMA
*Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi 110 062, India.
(Received: December 21, 2009 - Accepted: July 13, 2010)
ABSTRACT
Some 4-[{1-(substituted)methylidine}-amino]-3-(4-pyridyl)-5-mercapto-4H-1,2,4-triazol (3a- 3f) and N-[5-(4-substituted)-1H-1,2,3-triazol-1-yl]isonicotin-
amide derivatives (5a- 5e) were synthesized by a sequence of reactions starting from isonicotinic acid hydrazide and is illustrated in scheme 1 and 2. The antibacte-
rial and antifungal activities of newly synthesized compounds were tested by the disc diffusion method using nutrient agar medium against various microorganisms
such as gram positive Staphylococcus aureus and Bacillus subtilis, gram negative Escherichia coli and the fungi Aspergillus niger and Candida albicans. Cipro-
floxacin and Fluconazole at 50 μg/mLwere used as standard drugs for antibacterial and antifungal activities, respectively. All the synthesized compounds showed
significant activity against various microorganisms.
Key words: Triazole derivatives, Antimicrobial activity, Ciprofloxacin, Fluconazole.
cipitate obtained was filtered, dried in vacuum and recrystallised from ethanol
to give compound 3a-3f. The compounds were synthesized as illustrated in
scheme 113.
INTRODUCTION
Since the past few decades, the literature has been enriched with progres-
sive findings about the synthesis and pharmacological activities of various
substituted azole derivatives. It reveals that 1,2,4 and 1,2,3-triazoles possess
broad spectrum of activities such as antimicrobial1-4, anti-inflammatory5, an-
algesic6, antitumorial7, antihypertensives8, anticonvulsant and antiviral9. Some
of the antimicrobial triazole derivatives used as common antibiotics such as
Amphotericin B possess toxic effect on humans along with their antimicrobial
effects10. Although there are antimicrobial agents having different structures
are frequently used in the treatment of fungal infections, so there is increasing
resistance to these drugs. To overcome the development of drug resistance, it
is necessary to synthesize a new class of antimicrobial compounds possessing
different chemical properties from those that are used commonly. 5-Thioxo-
1,2,4-triazole containing a substituted aromatic aldehyde side chain is a ideal
heterocyclic for antifungal activity. The following antifungal 1,2,4-triazole
derivatives are applicable in medicine like Fluconazole, Itraconazole and Ter-
conazole11.
Scheme 1. 4-[{1-(substituted)methylidine}-amino]-3-(4-pyridyl)-5-mer-
capto-4H-1,2,4-triazol derivatives (3a-e).
EXPERIMENTAL
General procedure for synthesis of N-[5-(4-substituted)-1H-1,2,3-tri-
azol-1-yl]isonicotinamide derivatives (5a-5e)
The chemical reactives were supplied by E. Merck (Germany) and S.D
Fine chemicals (India). Melting points were determined by open tube capillary
method and were uncorrected. The purity of the compounds was checked on
thin layer chromatography (TLC) plates (silica gel G) in toluene-ethyl formate-
formic acid (5:4:1) and benzene-methanol (8:2) solvent systems, the spots
were located under iodine vapors and UV light. IR spectra were obtained on a
Isonicotinic acid hydrazide 1.37 g (0.01 mol) was dissolved in 30 mL etha-
nol and reacted with various equimolar substituted benzaldehyde derivatives
were added in presence of few drops of glacial acetic acid and refluxed for 5 h.
Then it was cooled, filtered and recrystallised from ethanol. This gave an inter-
mediate hydrazone compound, which was cyclised by passing freshly prepared
diazomethane gas to the dissolved compound in 1,4 dioxane. The solution was
allowed to stand for 24 h so that complete cyclisation took place, the product
obtained after cooling was recrystallised from 1,4 dioxane to yield compound
1
Perkin-Elmer 1720 FT-IR spectrometer (KBr pellets). H-NMR spectra were
recorded by a Bruker AC 300 MHz spectrometer using TMS as internal stan-
dard in DMSO-d6/CDCl3 and mass spectra under electron impact conditions
(EI) were recorded at 70 ev ionizing voltage with a VG Prospec instrument and
are presented as m/z. UV spectra were recorded on a UV-Visible Spectropho-
tometer Pharma Spec-1700 (SHIMADZU).
(5a-5e). The compounds were synthesized as is shown in scheme 214,15
.
Synthesis of 4-amino-3–(4-pyridyl)-5-mercapto-4H-1,2,4-triazol (2)
Isonicotinic acid hydrazide 13.7 g (0.1 mol) was dissolved in 200 mL ab-
solute alcohol containing potassium hydroxide 11.2 g (0.1 mol) at room tem-
perature 12.5 mL carbondisulfide was added in parts and was stirred for 16
hours at room temperature. 100 mL of diethyl ether was added and stirred for
further 3 h. 10.3 g (0.1 mol, 99%) hydrazine hydrate was added gradually to
the potassium dithiocarbazinate salt dissolved in 100 mL water with stirring
and was refluxed for 8 h during which hydrogen sulphide gas evolved and the
colour of the reaction mixture changed to deep green. It was then cooled and
acidified with hydrochloric acid to pH 1. The yellow colored solid was isolated
by filtration and recrystallised from ethanol to give compound (2)12
.
General procedure for synthesis of 4-[{1-(substituted)methylidine}-
amino]-3-(4-pyridyl)-5-mercapto-4H-1,2,4-triazol derivatives (3a- 3f)
Few drops of glacial acetic acid were added to a solution of 0.01 mol of
compound 2 (4-amino-3-(4-pyridyl)-5-mercapto-4H-1,2,4-triazol) in dimeth-
ylformamide (20 mL) and 0.01 mol of various benzaldehyde derivatives was
added and refluxed for 9 hours. The reaction mixture was cooled and the pre-
Scheme 2. N-[5-(4-substituted)-1H-1,2,3-triazol-1-yl]isonicotinamide de-
rivatives (5a-e).
e-mail: ravi_kcp@rediffmail.com
359

J. Chil. Chem. Soc., 55, Nº 3 (2010)
Data Analysis
(C-O-CH3 stretching), 1644 (C=O stretching), 1598 (C=N stretching), 1371
(C-N stretching); 1H NMR (400 MHz DMSO-d6 δ ppm) 3.93 [s, 6H, (CH )2],
7.10 (s, 1H, C-H of triazole), 7.68-8.77 (m, 7H, aromatic protons), 10.453 (s,
1H, CONH); Anal. calcd. for C16H9N5O: C, 63.82; H, 5.00; N, 19.85. Found:
C, 63.79; H, 5.04; N, 19.83. FABMS (m/z) 324(M+), 325(M++1). Mol. Wt.:
325.
4[{1-(4’-chlorophenyl)methylidine}amino]-3-(4-pyridyl)-5-mercapto-
4-1,2,4-triazole, (3a), colourless solid, yield 44%, mp 276-278°C, Rf 0.76, UV
λmax (DMF) 245.8 nm; FTIR (KBr) ν cm-1 3013 (Ar C-H stretching) , 2563
(S-H stretching), 1603, 1485 (Ar C=C stretching), 1563 (C=N stretching),
1313 (C-N stretching), 828 (C-Cl stretching), 688 (C-S stretching); 1H NMR
(400 MHz DMSO-d6 δ ppm) 6.06 (s, 1H, N=CH), 7.59-8.76 (m, 8H, aromatic
protons), 12.59 (s, 1H, S-H). Anal. calcd. for C14H10N5SCl: C, 54.30; H, 4.25;
N, 21.11. Found: C, 54.34; H, 4.21; N, 21.09. FABMS (m/z) 314(M+), 315
(M++1). Mol. Wt.:315.
N-[5-(3’-nitrophenyl)-1H-1,2,3-triazol-1-yl]isonicotinamide, (5d), co-
lourless solid, yield 69%, mp 222-224°C, Rf 0.83, UV λmax (DMF) 292.6 nm;
FT IR (KBr) ν cm-1 3439 (NH stretching of CONH), 3009 (Ar C-H), 1678
1
(C=O stretching), 1560 (C=N), 1516 (NO2 stretching); H NMR (400 MHz
4- [{1-(4’-dimethylaminophenyl) methylidine}amino] -3 -(4-pyridyl)-
5-mercapto-4H-1,2,4-triazole, (3b), colourless solid, yield 31%, mp 224-
226°C, Rf 0.82, UV λmax (DMF) 260.7 nm; FTIR (KBr) ν cm-1 3132 (Ar C-H
stretching), 2544 (S-H stretching ), 1523 (C=N stretching), 1344 (C-N stretch-
ing), 671 cm-1 (C-S stretching); 1H NMR (400 MHz DMSO-d6 δ ppm) 3.20 [s,
6H, N(CH ) ], 8.08 (s, 1H, N=CH), 7.59-8.78 (m, 8H, aromatic protons), 12.32
(s, 1H, SH3).2Anal. calcd. for C15H16N6S: C, 57.67; H, 5.16; N, 26.90. Found: C,
57.64; H, 5.18; N, 26.93. FABMS (m/z) 323 (M+), 324(M++1). Mol. Wt.: 324.
4-[{ 1-(3’-nitrophenyl)methylidine}amino]-3-(4-pyridyl)-5-mercapto-
4H-1,2,4-triazol e, (3c), colourless solid, yield 66%, mp 288-290°C, Rf 0.79,
UV λ (DMF) 221.9 nm; FTIR (KBr) ν cm-1 3033 (Ar C-H stretching), 2579
(S-H msatxretching), 1609, 1585, 1452 (Ar C=C stretching), 1520 (C=N stretch-
ing), 1353 (Ar-NO ), 1315 (C-N stretching), 698 cm-1 (C-S stretching); 1H
NMR (400 MHz D2MSO-d δ ppm) 5.58 (s, 1H, N=CH), 7.78-8.71 (m, 8H,
aromatic protons), 14.02 (s,61H , S-H). Anal. calcd. for C14H10N6SO2: C, 51.53;
H, 3.09; N, 25.02. Found: C, 51.52; H, 3.12; N, 25.14. FABMS (m/z) 325(M+),
326(M++1). Mol. Wt.: 326.
DMSO-d δ ppm) 5.56 (s, 1H, CH of triazole), 7.59-9.28 (m, 8H, aromatic pro-
tons), 12.630 (s, 1H, CONH). Anal. calcd for C14H10N5O3: C, 58.43; H, 3.39; N,
26.21. Found: C, 58.47; H, 3.34; N, 26.25. FABMS (m/z) 309(M+), 310(M++1).
Mol. Wt.: 310.
N-[5-(2’-nitrophenyl)-1H-1,2,3-triazol-1-yl]isonicotinamide, (5e), co-
lourless solid, yield 81%, mp 218-220°C; Rf : 0.77, UV λmax (DMF) 288.7nm.
FTIR (KBr) ν cm-1 3441 (NH stretching of CONH), 3019 (Ar C-H stretching),
1681 (C=O stretching), 1564 (C=N stretching), 1512 (NO2 stretching), 1348
1
(C-N stretching); H NMR (400 MHz DMSO-d6 δ ppm) 5.85 (s, 1H, CH of
triazole), 7.54-7.80 (m, 8H, Ar C-H), 11.02 (s, 1H, CONH). Anal. calcd for
C14H10N5O3: C, 58.43; H, 3.39; N, 26.21. Found: C, 58.40; H, 3.35; N, 26.24.
FABMS (m/z) 309 (M+), 310(M++1). Mol. Wt.: 310.
In vitro antibacterial activity
The primary screen was carried out using the agar disc-diffusion method16
using Muller–Hinton agar medium. Sterile filter paper discs moistened with
the test compound solution in dimethylsulfoxide at concentration of 200 µg/
mL were carefully placed on the agar cultures plates that had been previously
inoculated separately with the microorganisms17,18. The plates were incubated
at 37ºC. The synthesized compounds were tested for their in vitro antimicro-
bial activity against the Gram-positive bacteria S. aureus ATCC 19433 and
B. subtilis ATCC 6633, the Gram-negative bacteria E. coli ATCC 25922, and
the filamentous fungus A. niger ATCC 1034 and yeast-like pathogenic fungus
C. albicans ATCC 753. The standards, Ciprofloxacin and Fluconazole were
dissolved in dimethylsulfoxide at concentration of 800 µg/mL. The microor-
ganism suspensions at 106 CFU/mL (colony forming unit/mL) concentrations
were inoculated to the corresponding wells. The Petri plates were incubated at
36ºC for 24 and 48 h for the bacteria and fungi, respectively. The MIC values
were determined as the lowest concentration that completely inhibited visible
growth of the microorganism as detected by unaided eye. The diameters of the
growth inhibition zones were measured after 24 h for all microorganisms but
after 48 h in case of C. albicans.
4-[{1-(3’-hydroxyphenyl)methylidine}amino]-3-(4-pyridyl)
-5-mer-
capto-4H-1,2,4-triazole, (3d), colourless solid, yield 62%, mp 282-284°C,
Rf 0.66, UV λ (DMF) 234.6 nm; FTIR (KBr) ν cm-13450 (O-H stretching),
3032 (Ar C-Hmsatxretching), 2579 (S-H stretching), 1609, 1585, 1453 (Ar C=C
stretching), 1546 (C=N stretching), 1315 (C-N stretching), 699 (C-S stretch-
ing); 1H NMR (400 MHz DMSO-d6 δ ppm) 5.64 (s, 1H, N=CH), 7.82 (s, 1H,
O-H), 7.86-8.72 (m, 8H, aromatic protons), 13.96 (s, 1H, S-H). Anal. calcd. for
C14H11N5SO: C, 56.55; H, 3.73; N, 23.10. Found: C, 56.58; H, 3.76; N, 23.13.
FABMS (m/z) 296(M+), 297(M++1). Mol. Wt.: 297.
4-[{1-(4’-methoxyphenyl)methylidine}amino]-3-(4-pyridyl)-5-mer-
capto-4H-1,2,4-triazole, (3e), colourless solid, yield 50.8%, mp 272-274°C,
Rf 0.72, UV λ (DMF) 212.4 nm; FTIR (KBr) ν cm-1 3051 (Ar C-H stretch-
ing), 2872 (C-mOax-CH3), 2621 (S-H stretching), 1606 (Ar C=C stretching), 1541
(C=N stretching), 1377 (C-N stretching), 678 (C-S stretching); 1H NMR (400
MHz DMSO-d δ ppm) 3.79 (s, 3H, -O-CH ), 7.67 (s, 1H, N=CH), 7.25-7.80
(m, 8H, aromat6ic protons), 11.02 (s, 1H, SH3). Anal. calcd. for C15H13N5SO: C,
57.86; H, 4.21; N, 22.49. Found: C, 57.84; H, 4.22; N, 22.46. FABMS (m/z)
310 (M+), 311 (M++1). Mol. Wt.: 311.
Preparation of agar wells
A variety of devices such as stainless-steel or ceramic cylinders, single
or multiple in design, and paper discs of several sizes are commonly used for
antimicrobial assays performed by the agar diffusion method. Holes cut in agar
(agar wells) are occasionally useful for the assay of such materials as serum,
milk, eggs, or viscous materials. The routine use of agar wells is hampered by
the tedium of cutting and removing the agar plugs without disrupting the agar
layer19. Sealing the wells with melted agar is often necessary to obtain uniform
inhibition zones20. Agar wells are cut from seeded agar plates by a cylindrical
metal tube attached through a trap to a vacuum source. A section of a no. 4 cork
borer is a convenient cutter. A most important addition is a 1.5 mm diameter
hole in the side of the cutter, about 10 mm from the cutting edge, which acts
as a vacuum bypass and prevents tearing the agar from the bottom of the plate.
The agar plate is placed in the template on which are marked six evenly spaced
locations for the agar wells. The operator cuts the agar with rapid strokes, hold-
ing the cutter vertical to assure even contact with the base of the plate. Cutting
is greatly simplified if the plates are refrigerated at least 30 min prior to cutting.
The firmness of cold agar is very helpful. An agar layer 5 to 6 mm thick makes
convenient-size wells.
4-[{1-(3’-chlorophenyl)methylidine}amino]-3-(4-pyridyl)-5-mercapto-
4H-1,2,4- triazole, (3f), colourless solid, yield 51%, mp 296-298°C, R :
0.81, UV λmax (DMF) 240.6 nm; FTIR (KBr) ν cm-1 2975 (Ar C-H stretcfh-
ing), 2648 (S-H stretching), 1664 (Ar C=C), 1523 (C=N stretching), 1365
1
(C-N stretching), 815 (C-Cl stretching), 682 (C-S stretching). H NMR (400
MHz DMSO-d δ ppm) 5.69 (s, 1H, N=CH), 7.72- 7.90 (m, 4H, Aromatic pro-
tons) 8.01-8.136(m, 4H, aromatic protons), 12.49 (s, 1H, S-H). Anal. calcd. for
C14H10N5SC: C, 53.25; H, 3.19; N, 22.18. Found: C, 53.29; H, 3.17; N, 22.20.
FABMS (m/z) 314(M++1), 315(M++1). Mol. Wt.: 315.
N-[5-(4’-chlorophenyl)-1H-1,2,3-triazol 1-yl]isonicotinamide, (5a), co-
lourless solid, yield 70.01%, mp 202-204°C , R 0.73, UV λmax (DMF) 310.6
nm; FTIR (KBr) ν cm-1 3428 (N-H stretching)f, 3067 (Ar C-H stretching),
1664 (C=O stretching), 1550 (C=N), 1334 (C-N stretching), 818 (C-Cl stretch-
ing); 1H NMR (400 MHz DMSO-d6 δ ppm) 5.32 (s, 1H, CH of triazole), 7.64-
7.85 (m, 6H, aromatic protons), 8.06 (m, 2H, aromatic protons),11.83 (s, 1H,
CONH). Anal. calcd for C14H10N5OCl: C, 60.83; H, 3.53; N, 21.83. Found: C,
60.80; H, 3.54; N, 21.84. FABMS (m/z) 298 (M+), 299 (M++1). Mol. Wt.: 299.
N-[5-(4’-dimethylaminophenyl)-1H-1,2,3-triazol-1-yl]isonicotinamide,
(5b), colourless solid, yield 77%, mp 196-198°C, Rf 0.77, UV λ (DMF)
363.2 nm; FTIR (KBr) ν cm-1 3421(N-H stretching), 3067 (Ar Cm-Hax ), 1667
(C=O stretching), 1597 (C=N stretching), 1393(C-N of triazole); 1H NMR (400
MHz DMSO-d δ ppm) 3.20 (s, 6H, N(CH ) ), 5.58 ( s, 1H, C-H of triazole),
7.59-9.28 ( m, 68H, aromatic protons), 11.6372(s, 1H, CONH). Anal. calcd. for
C16H16N6O: C, 67.90; H, 5.70; N, 26.24. Found: C, 67.91; H, 5.73; N, 26.39.
FABMS (m/z) 307 (M+), 308 (M++1). Mol. Wt.:308.
RESULTS AND DISCUSSION
Chemistry
The synthesis of compounds 3a-f and 5a-e were undertaken as per the
scheme 1 and 2. The required 4-amino-3-(4-pyridyl)-5-mercapto-4H-1,2,4-tri-
azol (2) was prepared by the action of isonicotinic acid hydrazide and carbodi-
sulfide. The various 4-[{1-(substituted)methylidine}-amino]-3-(4-pyridyl)-5-
mercapto-4H-1,2,4-triazol derivatives (3a-f) were synthesized by condensation
of 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol with various aromatic
aldehydes in dimethyl formamide, in a yield ranging between 31 to 68%. Some
N-[5-(4-substituted)-1H-1,2,3-triazol-1-yl]isonicotinamide derivatives (5a-e)
were synthesized by a sequence of reactions starting from isonicotinic acid
N-[5-(3’,4’-dimethoxyphenyl)-1H-1,2,3-triazol-1-yl]isonicotinamide,
(5c), colourless solid, yield 68%, mp 172°C, Rf 0.77, UV λmax (DMF) 363.2
nm; FTIR (KBr) ν cm-1 3428 (N-H stretching), 3044 (Ar C-H stretching), 2835
360

J. Chil. Chem. Soc., 55, Nº 3 (2010)
1
hydrazide with aromatic aldehydes in glacial acetic acid. H-NMR, Mass and
or weak activity against C. albicans and A. niger. The results indicated that
the longer the side chain of a compound, the more antimicrobial activity it
possesses. Among the benzene ring ortho-substitution series, methyl deriva-
tives are more active than the hydroxyl and methoxyl substituted derivatives.
However, all the tested compounds exhibited low antifungal activity against C.
albicans. Moreover, the compounds 3b, 5a, 5b having the side chain showed
higher activity than oxime-ether derivatives with the same side chain against
S. aureus. This bioisosteric replacement resulted in a slightly increased an-
timicrobial activity. Our study revealed that all the compounds had stronger
antibacterial activity against Gram positive bacteria when compared to Gram
negative bacteria. The reason for the weaker antifungal activity according to
antibacterial effect might be postulated as different action in the mechanism
of the compounds such as inhibition effect on respiratory systems of fungal
cells, rather than cell wall destruction. The antimicrobial activity revealed that
newly synthesized compound 3b, 5a and 5b showed good significant activity.
The results of the preliminary antimicrobial testing of the prepared compounds,
the typical broad spectrum antibacterial drug Ciprofloxacin (50 µg/mL) and
the potent antifungal drug Fluconazole (50µg/mL) are shown in Table 1 and 2.
IR spectra were recorded on Bruker DRX-300 (300 MHz), MS Jeol SX-102
(FAB) and BIORAD FTIR Spectrometer instruments respectively. The ele-
mental analysis data of compounds was found to be within ±0.4 % limit. The
IR spectra of final compounds (3a-f) and (5a-e) showed absorption bands at
2544-2648 cm-1 and 1644-1681 cm-1 appearing due to the presence of a C=O
functional group and a SH functional group respectively, while the band ob-
served at 1516-1598 cm-1 corresponds to C=N linkage. Through the 1 H-NMR
spectra the synthesis of the compounds (3a-f) was confirmed on the basis that
-SH proton which was observed as singlet at δ 11.02 - δ 14.02. The CONH pro-
ton resonated in compounds (5a-e) at δ values between 11.02-14.02 as singlet
to broad singlet and this signal was absent when 1H-NMR was recorded in the
presence of D2O.
Antimicrobial activity
The results revealed that majority of the synthesized compounds showed
varying degrees of inhibition against the tested microorganisms. In general,
the inhibitory activity against the tested gram-positive bacteria was higher than
that of the gram-negative bacteria, and some derivatives showed moderate
Table 1- Antibacterial activity of compounds.
Diameter of zone of inhibition (mm)
Bacillus subtilis
Escherichia coli
Staphylococcus aureus
100mg
ml-1
Compd. No.
2
25 mg ml-1
50 mg ml-1
100 mg ml-1
25 mg ml-1
50 mg ml-1
100mg ml-1
25 mg ml-1
50 mg ml-1
10.76 ±0.15
13.83 ±0.20
4.93
±0.26
15.23
±0.15
4.46
±0.30
14.36
±0.15
16.6
±0.20
9.86 ±0.15
8.8 ±0.20
4.66 ±0.20
8.63 ±0.15
16.13
±0.05
8.23
±0.15
19.33
±0.20
20.23
±0.20
3a
8.16 ±0.20
20.6 ±0.20
13.16 ±0.10
10.8
±0.20
17.86
±0.12
22.83
±0.15
8.93
±0.15
14.80
±0.15
9.4
± 0.20
16.4
±0.10
21.3
±0.10
3b
20.26 ±0.15
7.8
±0.20
14.96
±0.20
19.71
±0.20
7.9
±0.10
13.83
±0.25
18.16
±0.20
14.63
±0.15
19.96
±0.15
3c
8.40 ±0.10
7.8 ±0.20
7.1
±0.10
14.13
±0.15
19.7
±0.10
7.76
±0.15
12.8
±0.20
18.13
±0.05
12.63
±0.05
19.06
±0.25
3d
11.66
±0.11
18.26
±0.12
9.76
±0.15
15.63
±0.20
20.8
±0.10
10.3
±0.10
17.36
±0.15
22.4
±0.20
3e
23.83 ±0.15
18.9 ±0.10
22.8 ±0.20
6.9
±0.10
5.33
±0.56
11.45
±0.37
16.45
±0.00
12.56
±0.05
3f
12.93 ±0.15
6.71 ±0.26
18.6 ±0.20
23.7 ±0.10
18.86
±0.12
10.33
±0.20
14.7
±0.30
10.63
±0.15
17.4
±0.20
5a
9.13 ±0.10
20.9 ±0.20
10.9
±0.15
19.7
±0.26
23.3
±0.17
10.2
±0.17
15.16
±0.10
21.16
±0.10
19.6
±0.20
24.83
±0.15
5b
10.76 ±0.15
5.9
±0.10
10.76
±0.15
16.53
±0.12
4.43
±0.15
11.36
±0.21
17.73
±0.25
6.16
±0.15
11.63
±0.15
17.86
±0.11
5c
9.06
±0.15
16.23
±0.15
21.03
±0.15
8.13
±0.13
14.13
±0.10
20.6
±0.20
16.7
±0.26
22.71
±0.26
5d
5e
9.7 ±0.10
11.03
±0.15
5.7
±0.10
10.7
±0.26
6.63
±0.15
12.70
±0.26
18.86
±0.12
6.33 ±0.20
18.7 ±0.10
15.33 ±0.20
26.76
±0.15
33.8
±0.20
23.32
±0.20
29.7
±0.26
25.63
±0.15
33.43
±0.15
Ciprofloxacin
Ciprofloxacin was used as standard drug at 50 mg/ml. All the values are in Mean ± S.D (n=3). Statistical analysis of data was carried out by one-way ANOVA.
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J. Chil. Chem. Soc., 55, Nº 3 (2010)
Table 2- Antifungal activity of compounds.
Diameter of zone of inhibition (mm)
Candida albicans
Aspergillus niger
Compound
25 mg ml-1
No.
50 mg ml-1
100 mg ml-1
19.33 ±0.11
25 mg ml-1
6.66±0.11
50 mg ml-1
100 mg ml-1
18.16 ±0.20
2
7.16 ±0.15
9.46±0.30
10.5±0.10
9.17 ±0.20
10.3±0.10
11.3±0.10
9.2±0.20
12.5 ±0.10
15.7 ±0.26
16.53±0.31
14.6 ±0.10
13.16 ±0.05
17.6 ±0.20
14.23 ±0.25
18.1 ±0.10
18.0 ±0.10
15.16±0.20
17.23±0.15
11.76±0.05
15.36 ±0.05
15.63±0.20
13.2±0.20
3a
3b
3c
3d
3e
3f
21.13 ±0.05
22.7 ±0.10
20.7 ±0.26
21.7 ±0.26
24.46 ±0.25
20.46 ±0.11
24.16 ±0.15
23.1±0.10
8.93±0.05
10.33±0.41
8.6±0.20
20.16 ±0.20
22.16 ±0.20
20.16 ±0.20
21.23 ±0.25
23.8 ±0.20
20.23 ±0.15
23.73 ±0.05
22.3 ±0.32
20.5 ±0.10
22.16 ±0.20
9.73 ±0.30
11.03±0.05
8.7±0.26
16.36±0.20
17.6 ±0.05
14.16 ±0.20
17.2 ±0.20
16.56±0.32
14.3±0.26
5a
5b
5c
5d
11.13±0.15
10.6 ±0.20
8.63±0.20
10.26 ±0.15
9.4 ±0.20
10.7 ±0.10
10.2 ±0.10
8.23±0.15
9.6±0.20
21.23 ±0.15
23.53±0.46
16.16±0.20
5e
15.43±0.20
24.16±0.20
22.2±0.10
9.13±0.15
15.63 ±0.20
23.5±0.10
21.63±0.20
30.23±0.15
Fluconazole
31.56±0.32
Fluconazole was used as standard at 50 mg/ml. Data are given as Mean ± S.D. (n=3). Statistical analysis of data was carried out by paired t- test.
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CONCLUSIONS
Various 4-[{1-(substituted)methylidine}-amino]-3-(4-pyridyl)-5-mercap-
to-4H-1,2,4-triazol and N-[5-(4-substituted)-1H-1,2,3-triazol-1-yl]isonico-
tinamide derivatives were synthesized from isonicotinic acid hydrazide. The
structure antimicrobial activity relationship of the synthesized compounds,
based on the structures of the final compound, which possessed good anti-
microbial activity, revealed that the introduction of an aryl moiety generally
reduced the antimicrobial activity according to the nature of the aryl moiety.
The antimicrobial activities including antibacterial and antifungal properties
of the synthesized compounds showed a significant activity as compared with
standard drugs.
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