Research Article ISSN: 0974-6943

Ghosh Swagatika et al. / Journal of Pharmacy Research 2009, 2(7),1237-1239

Available online through www.jpronline.info

Synthesis, characterisation and antifungal activity of some new 1, 2, 4 - triazolophenyl quinoline derivatives
Ghosh Swagatika*, Kumar Mandal Milan1, Banerjee Mritunjay1, Patro Saroj1, Kanungo Sunil1. *United Institute of Pharmacy, UCER, Industrial Area, Naini, Allahabad, U.P. 211 010. 1Department of Pharmaceutical Chemistry, Institute of Pharmacy & Technology, Salipur, Cuttack, Orissa, India 754 202. Received on: 09-03-2009; Accepted on: 26-05-2009 ABSTRACT A series of new 1,2,4-Triazole Phenylquinoline derivatives were synthesized by condensation of Aniline derivatives with Cinnamic Acid followed by cyclisation reaction with Hydrazine Hydrate & formic acid respectively via Schiff base formation and the structure of these compound were established on the basis of spectral and elemental analysis. All the compounds were screened for Antimicrobial activity and the synthesized compounds showed promising antimicrobial activity as compared with the standard drug Fluconazole. Keywords: 1, 2, 4-Triazolophenylquinoline, Aniline, Antifungal. INTRODUCTION The art of synthetic chemistry has always been a significant tool to design pharmacoactive molecules. A vast amount of pioneering work has been reported for synthesis and structure activity relation ship of Triazole ring structure in the last few decades. The discovery, development & identification of biologically active compounds at molecular level is gaining importance to any drug industry. Literature survey reveals that a large number of Triazole 1 , Thiadiazole 10 & Trizolothiadiazine6 particularly substituted at position 3 & 6 by aryl alkyl or heterocyclic moieties have been reported to posses CNS depressant, antibacterial7,9,antifungal8,anti-HIV,antitumor, anti-inflammatory activities 3, in addition to herbicidal, pesticidal & insecticidal properties. Also a number of quinoxaline2 derivatives have been shown to posses a variety of pharmacological properties like antibacterial, antifungal5, analgesic & hence it is found to be an important structural feature in some synthetic drugs. Therefore it was thought to combine phenyl quinoline6 moiety with 1, 2, 4-Trizolo 5 rings together in a molecular framework to see the additive effects of these rings towards biological activity. MATERIALS AND METHODS All the chemicals and solvents which were used are of AR grade & IR grade purchased from Himedia, Burgoyne Burbidges, Merk Mumbai & Bengal chemical & Pharmaceuticals Kolkata. General Procedure In the present work new 1,2,4-Triazole Molecules were synthesized using Schiff Base reaction3,7 by conventional method(scheme-1). Melting points were determined in open capillary method and are uncorrected. Purity of the compounds was checked on Silicagel-G TLC plates. IR spectra were recorded on Fourier Transform Infrared *Corresponding author. Tel.: + 91-9919698663 E-mail: swagatikaghosh@yahoo.co.in Spectrophotometer (FTIR 8400S, Schimadzu) using KBr disc method. 1HNMRspectra were recorded on Bruker DRX 300 MHz FT NMR with low and high temperature facility (-90oC - +80oC). The solvents used were CDCl3 & DMF for 1HNMR & graph of the specific samples were obtained. Synthesis of 4-phenylquinolin-2(1H)-one. (P1) Equimolar quantity i. e. 0.05 mol of Cinnamic acid (7.4gm) and aniline (4.7gm) were taken in a round bottom flask. Then to it 15 ml of ethanol was added. Then it was refluxed for about 5 hour. Then the whole concentrate was transferred to a beaker by filtration. Then a clear brownish colored liquid was obtained & it was kept for overnight which produced white solid transparent flakes of crystals, after draining out the mother liquor. Then it was recrystallized with ethanol. The yield obtained was 50%. (Scheme1) Synthesis of (2E)-4-phenylquinolin-2(1H)-one hydrazone. (2P1) Equimolar quantity i. e. 0.005 mol of compound P1 and hydrazine hydrate were taken in a round bottom flask. Then to it 20 ml of ethanol was added. It was refluxed for about 5 hour. The whole concentrate was transferred to a beaker by filtration. The filtrate was then warmed & to it crushed ice were added. Then it was recrystallized with ethanol. The yield obtained was 70%.(Scheme1) Synthesis of 5-phenyl-3,3a-dihydro [1, 2, 4]triazolo[4,3-a]quinoline. (3P1) Equimolar quantity i. e. 0.025 mol of compound 2P1 and formic acid were taken in a round bottom flask. Then to it 20 ml of ethanol was added with constant stirring. It was refluxed for about 6.5 hour. Then the whole concentrate was transferred to a beaker by filtration. The filtrate was then warmed & to it crushed ice were added, slowly crystal growth was seen. Then it was recrystallized with ethanol. The yield was obtained 60%.(Scheme1) Synthesis of 8-chloro-4-phenyl quinolin-2(1H)-one. (P2) Equimolar quantity i. e. 0.05 mol of Cinnamic acid (7.4gm) and Chloro aniline (4.7gm) were taken in a round bottom flask. Then to it 15 ml of ethanol was added. Then it was refluxed for about 6 hour. The whole

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Ghosh Swagatika et al. / Journal of Pharmacy Research 2009, 2(7),1237-1239 Scheme 1

O N H2 OH

Scheme - 2
Cl NH 2 O OH

+
(2 E ) - 3 - p h e n y l a c r y l i c a c i d aniline
ethanol

+
2-chloroaniline (2 E )-3-phenylacrylic acid
ethanol

H N

Cl

H N

O H2N NH2

H2N

N H2

hydrazine
ethanol

hydrazine

( P1 ) H N

ethanol ( P2 ) Cl H N

N NH 2 H

NH 2 H

+
( 2P1 )

O OH

+
( 2P2 )

O OH

formic acid

formic acid
ethanol

ethanol

Cl

N NH

N NH

( 3P1 )

( 3P2 )

Table 1: Physical & Chemical Data of compound Synthesized.

Compd. Yield m.p. (%) C P1 50 115C P2 2P1 2P2 3P1 3P2 54 70 65 60 65 120C 120C 115C 121C 123C Mol.Formula C15H11NO C15H10ClNO C15H13N3 C15H12ClN3 C16H13N3 C16H12ClN3 Rf Mol.Wt. Value 0.67 221.254 0.61 0.63 0.67 0.62 0.69 255.700 235.284 269.729 247.295 281.740 Calcd. C 81.43 (81.52) 70.46 (70.49) 76.57 (76.50) 66.76 (66.70) 77.71 (77.70) 68.21 (68.20) % (Found) H N 5.01 6.33 (5.02) (6.35) 3.96 5.48 (3.91) (5.5) 5.77 17.86 (5.90) (17.89) 4.48 15.58 (4.46) (15.60) 5.30 16.99 (5.34) (17.10) 4.29 14.91 (4.30) (14.90)

concentrate was transferred to a beaker by filtration. Then a clear brownish colored liquid was obtained & then it was kept for overnight which produced white solid transparent flakes of crystals after draining out the mother liquor. Then the product was recrystallized with ethanol. The yield was obtained 54%. (Scheme2)

Synthesis of (2E)-8-chloro-4-pheny l quinolin-2(1H)-one hydrazone. (2P2) Equimolar quantity i. e. 0.005 mol of compound P2 and hydrazine hydrate were taken in a round bottom flask. Then to it 20 ml of ethanol was added with constant stirring. Then it was refluxed for about 7

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Table 2: Spectral Data of compound Synthesized.

IR (cm-1) (Neat) 2P1 3598(-NH2-), 1731(C=N), 3026(CH=CH) 2P2 703(C-Cl), 1685(C=N), 3631(-NH2-) 3P1 1680(C=N), 3625(-NH-), 750(Ar-ring) 3P2 1681(C=N), 3631(-NH2-), 871.6(mono subsited benzene), 972(Triazo) Table 3: Minimal Inhibitory Concentration Compd.
Compd. 2P1 2P2 3P1 3P2 Control Fluconazole Candida albicans (1g/ml) (2g/ml) (4g/ml) ++ + ++ ++ + ++ ++ ++ ++ ++

HNMR (300 MHz, CDCl 3 & DMF) ( ppm) 3P1 6.44(d,H,CH=C), 6.9(S,1H,NH), 7.4(1H,CH), 7.8(m, Ar-H) 3P2 6.43(d,H,CH=C), 7.41(S,1H,CH) 7.83(m, Ar-H),

Aspergillus niger (1g/ml) (2g/ml) (4g/ml) ++ + ++ ++ ++ ++ ++ ++ ++ +

++: Denotes the growth, +-: Denotes the growth with less than 20 colonies, : Denotes no growth. Table 4: Zone of Inhibition (cm)
Compd. 2P1 2P2 3P1 3P2 Control Fluconazole (1g/ml) 0.9 1.2 1.2 1.3 0.0 0.8 Candida albicans Aspergillus niger (2g/ml) (4g/ml) (1g/ml) (2g/ml) (4g/ml) 1.3 1.6 1.1 1.3 1.3 1.4 1.9 1.1 1.2 1.4 1.3 1.8 1.2 1.5 1.8 1.3 1.5 0.9 1.2 1.3 0.0 0.0 0.0 0.0 0.0 1.4 1.6 0.8 1.2 1.6

hour. The filtrate was then warmed & to it crushed ice were added which showed slow crystal growth. Then it was recrystallized with ethanol. The yield was obtained 65%.(Scheme2) Synthesis of 9-chloro-5-phenyl-3,3a-di hydro[1,2,4]triazolo[4,3a]quinoline. (3P2) Equimolar quantity i. e 0.025 mol of compound 2P2 and formic acid were taken in a round bottom flask. Then to it 20 ml of ethanol was added with constant stirring. It was refluxed for about 6 hour. Then the whole concentrate was transferred to a beaker by filtration. The filtrate was then warmed & to it suddenly crushed ice were added. Slowly crystal growth was seen. Then it was recrystallized with ethanol and acetone. The yield was obtained 70%. (Scheme2). RESULTS & DISCUSSION The synthesized compounds were purified and the purity of all the compounds was checked by melting point determination and TLC (Table 1). The structures of these compounds were ascertained by finding prominent peaks in IR, 1H NMR spectral data (Table 2). The purified compounds were screened for antifungal activity was found satisfactory by almost all the compounds as compared with standard Fluconazole. The compounds 2P1, 3P1 & 2P2 were more potent (Table 3, 4). CONCLUSION All the compounds synthesized were screened for antifungal activity by tube dilution & agar diffusion method. Compound code 2P1, 3P1 & 2P2 have shown promising antifungal activity against the microbes compared with the standard drug Fluconazole and with the suitable molecular modification; potency of these compounds may be further increased.

ACKNOWLEDGEMENT: The author thanks to Sophisticated Analytical Instrument Facility, CDRI L c n w f r p o i i g1HNMR & C,H,N, analysis data, , uko, o rvdn I.P.T., Salipur for providing FTIR Data & other necessary facilities to carry out research work. The author is also grate full to Asst. Prof. M. Banerjee, Department of Pharmaceutical Chemistry, SOA University for providing necessary technical guidance.
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Source of support: Nil, Conflict of interest: None Declared Journal of Pharmacy Research Vol.2.Issue 7.July 2009

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