Synthesis, Characterization and Biological evaluation of some newer 5-[6-chloro/fluoro/nitro-2-(p-chloro/ fluoro/ methyl phenyl)-quinolin-4-yl]-1,3,4-oxadiazole-2-thiols

Available online at www.ilcpa.pl International Letters of Chemistry, Physics and Astronomy 6 (2014) 26-32 ISSN 2299-3843 Synthesis, Characterization and Biological evaluation of some newer 5-[6-chloro/fluoro/nitro-2(p-chloro/ fluoro/ methyl phenyl)-quinolin-4-yl]-1,3,4oxadiazole-2-thiols V. J. Faldu*, P. K. Talpara, N. H. Bhuva, P. R. Vachharajani, V. H. Shah Department of Chemistry, Saurashtra University, University Road, Rajkot 360 005, Gujarat, India *E-mail address: ABSTRACT Recent study shows that quinolines represent one of the most active classes of compounds possesses wide spectrum biodynamic activities and use as potent therapeutic agents. In present research work, 5-[6-chloro/fluoro/nitro-2-(p-chloro/fluoro/methyl phenyl)-quinolin-4-yl]-1,3,4oxadiazole-2-thiols have been synthesized by condensation of substituted quinoline-4carbohydrazides and mixture of carbon disulphide and potassium hydroxide. All of these compounds were screened for their in vitroanti microbial assay against gram (+ve), gram (-ve) bacteria and fungi activity compared with standard drugs viz., Ampicilin, Chloramphenicol, Ciprofloxacin, Norfloxacin, Griseofulvin and Nystatin at different concentrations. Keywords: Quinolines; 1,3,4-oxadiazole-2-thiols; therapeutic agents; anti-microbial assay 1. INTRODUCTION Tuberculosis (TB) is a global epidemic caused by various strains of mycobacterium, usually Mycobacterium tuberculosis (H37RV). Tuberculosis has been considered to be a disease of poverty for many years with quite rare occurrence in the developed countries. Unfortunately recently more people in the developed world are contracting tuberculosis because their immune systems are compromised by immunosuppressive drugs, substance abuse or AIDS. Several decades ago effective anti-TB drugs have been launched and one could hardly find a TB case to be demonstrated at the medicinal universities. But TB stroke back1. The return of tuberculosis was declared by World Health Organization (WHO) as a global emergency compared to a hypothetic third world war with 9 million new TB cases and two million deaths reported each year2,3; about one-third of the world’s population is already infected with M. tuberculosis.4 The quinoline was reported to exhibit various biological activity such as antiamoebic5, antimalarial6,7, antiviral8,9, as well as anti-inflammatory activity10,11. In addition, the International Letters of Chemistry, Physics and Astronomy 6 (2014) 26-32 discovery of nalidixic acid, a urinary tract antimicrobial drug12, prompted the synthesis of many quinoline derivatives and evaluation for their antimicrobial activity13-15and antibacterial activity. Norfloxacin, ofloxacin and ciprofloxacin (nalidixic acid analogs) were marketed as antibacterial agent16. Besides, oxadiazole rings are important examples of the heteroazoles that by themselves or in combination with other ring systems possess antimicrobial17-19,21 as well as antibacterial activity. In view of this fact and as a continuation of a research program carried out in our laboratory series of substituted oxadiazolyquinoline have been synthesized to investigate their antimicrobial activity and antitubercular activity. 2. RESULT AND DISCUSSION 2. 1. Chemistry Preparation of 5-(2-(4-chloro/flouro/methylphenyl)-6-fluoro/chloro/nitroquinoline-4yl)-1,3,4-oxadiazole-2-thiol (4a-i) is summarized in Scheme 1. Various 2-(4chloro/flouro/methylphenyl)-6-(fluoro/chloro/nitroquinoline)-4-carbohydrazide (3a-i) were treated with potassium hydroxide and carbon disulphide in ethanol was heated under reflux until the evolution of H2S ceases. The reaction mixture was concentrated and dissolved in water and acidified with HCl. The resulting product was recrystallised from methanol. The yields of the products were obtained in the range of 65-80 %. Designed series of molecules scheme-1 were characterized by 1H NMR, IR and Mass spectrometry techniques before evaluating for antimicrobacterial and antitubercular activity. HS O O OH R1 SOCl2 N 1(a-i) R R1 Cl O H2N NH2 2H2O R1 N R 2 (a-i) H N NH2 O KOH, CS2 R1 N 3 (a-i) R N R 4 (a-i) R= 4-Cl-C6H4, 4-F-C6H4, 4-CH3-C6H4 R1=4-F, 4-Cl, 4-NO2 Scheme 1. Comparative antimicrobial activity of 5-[6-chloro/fluoro/nitro-2-(p-chloro/ fluoro/ methyl phenyl)-quinolin-4-yl]-1,3,4-oxadiazole-2-thiols (4a-i). (Different Inhibition Concentration in μg/ml). 2. 2. Antimicrobial and antitubercular activity The products (4a-i) were assayed for their in vitro biological assay like antibacterial activity towards S. pyogens MTCC-442, S. aureus MTCC-96 (Gram positive) and E. coli MTCC- 443, P. aeruginosa MTCC-424 (Gram negative) bacterial strain and antifungal activity towards A. niger MTCC-282 and A. clavatus MTCC-1323 at different concentrations: i.e. 0 (control), 5, 25, 50, 100, 250 (μg/ml) for their MIC (Minimum Inhibitory Concentration) values. The biological activities of the synthesized compounds (Xa-i) were compared with standard drugs viz., Ampicilline, Chloramphenicol, Ciprofloxacin, Norfloxacin, Griseofulvin and Nystatin. The result of antimicrobial activity is 27 N N International Letters of Chemistry, Physics and Astronomy 6 (2014) 26-32 presented Table in given below bold value presented that, these compounds are biological active near or above than the standard drugs. Table 1 Antibacterial activity (Zone of inhibition in m.m.) S.Pyogens MTCC-442 S.aureus MTCC-96 5 25 50 100 250 5 25 50 100 250 4a 4-Cl-C6H4 4-F 09 14 17 15 19 13 14 19 4b 4-Cl-C6H4 4-Cl 10 13 15 17 10 12 16 18 4c 4-Cl-C6H4 4-NO2 10 12 14 16 11 13 14 17 4d 4-F-C6H4 4-F 11 13 14 17 11 13 17 16 4e 4-F-C6H4 4-Cl 09 11 14 10 13 15 16 19 4f 4-F-C6H4 4-NO2 10 13 14 18 12 13 17 16 4g 4-CH3-C6H4 4-F 11 13 15 18 09 11 14 19 4h 4-CH3-C6H4 4-Cl 10 14 17 10 13 14 20 18 4i 4-CH3-C6H4 4-NO2 11 14 09 14 18 20 17 20 Comparative activity of 4(a-i) with known chosen standard drugs Standard drug Antibacterial activity Ampicilline 11 14 19 18 19 10 13 14 16 18 Chloramphenicol 10 13 19 20 20 12 14 19 20 21 Ciprofloxacin 16 19 21 21 22 17 19 21 22 21 Norfloxacin 18 19 20 21 21 19 22 25 26 28 Entry R R1 Table 2 Antibacterial activity (Zone of inhibition in m.m.) Entry R R1 E.coli MTCC-443 P.aeruginose MTCC-424 5 25 50 100 250 5 25 50 100 250 4a 4-Cl-C6H4 4-F 12 13 14 15 15 17 20 21 4b 4-Cl-C6H4 4-Cl 12 13 17 19 13 15 19 18 4c 4-Cl-C6H4 4-NO2 14 17 10 12 13 15 16 21 4d 4-F-C6H4 4-F 11 12 15 10 13 15 17 21 4e 4-F-C6H4 4-Cl 12 15 12 14 16 19 19 21 4f 4-F-C6H4 4-NO2 14 17 18 11 15 16 18 16 4g 4-CH3-C6H4 4-F 12 13 15 17 12 14 16 18 4h 4-CH3-C6H4 4-Cl 18 11 14 16 19 15 17 20 4i 4-CH3-C6H4 4-NO2 10 12 16 17 15 17 19 22 Comparative activity of 4(a-i) with known chosen standard drugs Standard drug Antibacterial activity Ampicilline 14 15 16 19 20 14 15 15 18 20 Chloramphenicol 14 17 23 23 23 14 17 18 19 21 Ciprofloxacin 20 23 28 28 28 20 23 24 26 27 Norfloxacin 22 25 26 27 29 18 19 21 23 23 28 International Letters of Chemistry, Physics and Astronomy 6 (201 (...truncated)