Design Synthesis Characterization and Biological Evaluation of Novel Heterocyclic Derivatives as Anti Tubuercular Agents

Abstract

In the present work, simple and efficient practical methods for the synthesis of heterocyclics, which resulted from the in-silico approach was achieved in good yield. Chalcone derivatives of (furan-2yl)-3 derivatives, ie. Compounds HLA, M4F and ATRIM showed most potent inhibition in in-vitro anti-tubercular activity at MIC 0.1, 0.1, 0.2 and 1.6 and#956;g/ml concentrations. In-vivo acute toxicity studies and in-silico ADME predictions reports suggest the lead compounds HLA, M4F and ATRIM can be taken up for further studies. It was found that lead compound ATRIM was active in in-vivo antimycobacterial assay, when compared to the other synthesized tested compounds. The three methoxy group of ATRIM may be responsible to contribute for the better in-vivo activity results. The compound ATRIM is having 100% Oral absorption is as compared to other synthesized compounds HLA and M4F, which may give better invivo Anti-tb activity. ATRIM follows the rule of five with human serum albumin binding value (0.215) which is less as compared to HLA and M4F(02.34 and 0.248 respectively). It was interesting to note that the compound ATRIM decreased the bacterial load to 38.0±4.0 at 15 mg/kg dose, while standard drug isoniazid decreased the bacterial load to 16.7±2.5 at same dose. Thus the study deserves for the conclusion that the CFU value obtained by compound ATRIM at the dose of 15mg/kg was found to be significant when compared to the standard drug isoniazid at same dose. It was also concluded that, on increasing the dose of compound ATRIM, it may produce more or equal significant results compared to the standard drug isoniazid. The above results findings have demonstrated that, the compound ATRIM with IUPAC name (2E)-1-(furan-2-yl)-3-(3, 4, 5-trimethoxyphenyl) prop-2-en-1-one is possibly a good antitb agent. Designed, synthesized, characterized and biologically evaluated novel hetero cyclic derivatives as Anti - tuberculosis agents which inhibit target enzyme Fab D.