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

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]-1,3,4-oxadiazole-2-thiols have been synthesized by condensation of substituted quinoline-4-carbohydrazides and mixture of carbon disulphide and potassium hydroxide. All of these compounds were screened for their in vitro anti 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.


INTRODUCTION
Tuberculosis (TB) is a global epidemic caused by various strains of mycobacterium, usually Mycobacterium tuberculosis (H 37 RV). 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 back 1 . 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 year 2,3 ; 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 antiamoebic 5, antimalarial 6,7 , antiviral 8,9 , as well as anti-inflammatory activity 10,11 . In addition, the discovery of nalidixic acid, a urinary tract antimicrobial drug 12 , prompted the synthesis of many quinoline derivatives and evaluation for their antimicrobial activity [13][14][15] and antibacterial activity.
Norfloxacin, ofloxacin and ciprofloxacin (nalidixic acid analogs) were marketed as antibacterial agent 16 . Besides, oxadiazole rings are important examples of the heteroazoles that by themselves or in combination with other ring systems possess antimicrobial [17][18][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.

Antimicrobial and antitubercular activity
The products (4a-i) were assayed for their in vitro biological assay like antibacterial activity towards S.  Table in given below bold value presented that, these compounds are biological active near or above than the standard drugs.  All compounds were initially screened for their antitubercular activity at 6.25 μg/mL concentration against MTB H37Rv strain by the Tuberculosis Antimicrobial Acquisition & Coordinating Facility (TAACF) in BACTEC 12B medium using the Microplate Alamar Blue Assay 20 . Unfortunately In the preliminary screening all compounds (4a-i) were inactive against MABA assay and all compounds possess bothIC 50 > 100 and IC 90 > 100.

EXPERIMENTAL SECTION
All research chemicals were purchased from Sigma-Aldrich and used as such for the reactions. Reactions were monitored by thin-layer chromatography (TLC) on pre-coated silica gel GF254 plates from E-Merck Co and compounds visualized either by exposure to UV light or staining with reagents. Melting points were determined in open capillaries and are uncorrected. The IR spectra were recorded on SHIMADZU-FTIR-8400 spectrophotometer using KBr pellet method. 1 H NMR spectra were recorded on Bruker 300-MHz NMR spectrometer in CDCl 3 with TMS as internal standard. Mass spectrum was recorded on JOEL SX 102/DA-600-Mass spectrometer and elemental analysis was carried out using Heraus C, H, and N rapid analyzer

CONCLUSIONS
In the present paper, we report the synthesis, spectral studies and its Antimicrobial and antimycobacterial activity of various quinoline derivatives. The high bioactivity of these compounds makes them suitable hits for additional in vitro and in vivo evaluations, in order to develop new class of Antimicrobial and antimycobacterial drugs or prodrugs with potential use in the antibacterial, antifungal and tuberculosis treatment. Further studies in this area are in progress in our laboratory.