Design Synthesis and Anti Tubercular Evaluation of Novel Heterocycles

Abstract

Tuberculosis (TB) is a leading disease and a major cause of death which is predominantly newlinerelated to anti-tubercular (anti-TB) resistance acquired during the course of treatment. newlineGlobally, a large number of people have been found to develop multidrug resistance to TB newline(MDR-TB). New forms of MDR-TB and extensively drug-resistant TB (XDR-TB), pose a new newlinechallenge for the medicinal chemist to prepare novel derivatives by proper selection of novel newlinetargets having minimum cross-resistance with existing drugs. Thus, it is the need of the hour newlineto develop new anti-TB agents that could act via unique mechanisms and therefore show newlineminimum cross-resistance with the drugs prevailing in the market. newlineBy using different aspects of drug designing, several heterocyclic rings, reactions, and newlinetheir biological activities, it was planned to conduct a study on the following aspects to develop newlinea pharmacologically effective research molecule, especially for treating TB using INH as a lead newlinemolecule. The present study was aimed to design, synthesize, and screen novel heterocyclic newlinederivatives viz., thiazolidinone, pyrazolo-thiazole, thiazole, azetidinone, thiadiazole, and newlineisoxazole, which could improve the physicochemical, pharmaceutical or biopharmaceutical newlineand biological properties of drug molecules. newlineIn the first scheme, a series of heterocyclic thiazolidinone and their pyrazolo-thiazole newlinederivatives 3a-i and 4a-i were synthesized by facile condensation reaction of isoniazid (INH) newlineindependently with various aromatic aldehydes. All the synthesized compounds of the series newlinewere characterized by IR, 1HNMR, and Mass spectra and were evaluated for their in vitro newlineinhibitory activity against Mycobacterium tuberculosis H37Rv using the tube dilution method newlineand by employing INH and rifampicin as standard drugs. Compounds 3i and 4i showed good newlineactivity with MIC value of 25.25and#956;g/ml and compound 4i also exhibited activity with a MIC newlinevalue of 14.66and#956;g/ml. Compounds 3a, 3e, 4a, and 4e showed moderate anti-TB activity with newlineMIC values of 36.6, 40.50, 30.70, and 3