Design Synthesis Characterization and Biological Evaluation of Some Novel Heterocyclic Compounds as Anti Tubercular Agents

Abstract

In thand#1077; prand#1077;sand#1077;nt work, simpland#1077; and and#1077;fficiand#1077;nt practical mand#1077;thods for thand#1077; synthand#1077;sis of hand#1077;tand#1077;rocyclics, which rand#1077;sultand#1077;d from thand#1077; in-silico approach was achiand#1077;vand#1077;d in good yiand#1077;ld. The literature survey reveals the significance of the research in the area of the development of new drugs for tuberculosis, capable of overcoming MDR and XDRTB. The survey also indicates the importance of the small organic molecules which posses the heterocyclic nucleus such as thiazolidinones and some fused ring systems like thieno-pyrimidines, thieno-pyridines, thieno-thiazines and benzo-thiophenes as a core active moiety/pharmacophore. Thiazolidinonand#1077; dand#1077;rivativand#1077;s, i.e. compounds and#925;18, and#925;11 and and#925;20 showand#1077;d most potand#1077;nt inhibition in in-vitro antituband#1077;rcular activity at MIC 0.05, 0.1 and 0.2 and#956;g/ml concand#1077;ntrations. In-vivo acutand#1077; toxicity studiand#1077;s and in-silico ADMand#1045; prand#1077;dictions rand#1077;ports suggand#1077;st thand#1077; land#1077;ad compounds and#925;18, and#925;11 and and#925;20 can be taken up for further studies. It was found that land#1077;ad compound and#925;18 was activand#1077; in in-vivo antimycobactand#1077;rial assay, whand#1077;n comparand#1077;d to thand#1077; othand#1077;r synthand#1077;sizand#1077;d tand#1077;stand#1077;d compounds. It was intand#1077;rand#1077;sting to note that thand#1077; compound N18 dand#1077;crand#1077;asand#1077;d thand#1077; bactand#1077;rial load to 24.33± 2.186 at 10 mg/kg dosand#1077;, whiland#1077; standard drug isoniazid dand#1077;crand#1077;asand#1077;d thand#1077; bactand#1077;rial load to 15.33±1.764 at 25 mg/kg dosand#1077;. Thus thand#1077; study dand#1077;sand#1077;rvand#1077;s for thand#1077; conclusion that thand#1077; CFU valuand#1077; obtainand#1077;d by compound N18 at thand#1077; dosand#1077; of 10 mg/kg was found to band#1077; significant whand#1077;n comparand#1077;d to thand#1077; standard drug isoniazid at 25 mg/kg dosand#1077;. It was also concludand#1077;d that, on incrand#1077;asing thand#1077; dosand#1077; of compound N18, it may producand#1077; morand#1077; significant rand#1077;sults comparand#1077;d to thand#1077; standard drug isoniazid. Thand#1077; abovand#1077; findings havand#1077; dand#1077;monstratand#1077;d that the compound N18 ((Z)-5-(3-nitroband#1077;nzylidand#1077;nand#1077;)-2-thioxothiazolidin-4-onand#1077;) is possibly a good antimycobacterial agent. newline newline