Molecular modeling QSAR studies and synthesis of novel azolo cinnoline analogs as antitubercular agents

Abstract

Medicinal Chemistry concerns the discovery, development, identification and screening of the biologically active compounds at its molecular level, utilizing all branches of chemistry and biology. Heterocyclic ring is the unique basis for the activity of most of the drugs of natural origin and for the discovery of many synthetic drugs with versatile pharmacological action. Most of the synthetic drugs have resulted by simple or more involved modifications of the structures of the natural drugs, or by pure synthesis. The fused analogs of heterocyclic rings also have been represented in numerous natural products with biological and pharmaceutical activities, which indicate that on meticulous research heterocyclic derivatives will persist to yield novel medicinal agents. The current treatment of tuberculosis (TB) recommended by WHO is Directly observed treatment short course (DOTS) a standard chemotherapeutic regimen at least for six months. The inconvenience of this drug course has precluded rigorous adherence and led to the development of multidrug-resistant strains of Mycobacterium tuberculosis (MDR-TB) and a new phenomenal level of drug resistance, extensively drug resistant tuberculosis (XDR-TB) due to MTB bacilli s complex cell wall and nucleus. Conclusion: In this study In-silico design was developed to accelerate and assist hit identification, hit-to-lead selection, and lead optimisation. The computational tools were found to advance efficiency and effectiveness of drug discovery process, reduce use of animals and increase predictability of biological action. Computer-aided drug discovery and development utilised here was based on the incerebro-in silico-chemico-biological approach. Thus the molecular modelling studies of azolo cinnoline analogs by targeting the inhibition of enzyme cytochrome P450 14and#945;-sterol demethylase followed by its synthesis and in vitro screening for antitubercular and antifungal activity shown that azolo cinnoline analogs will be safe, fast acting, less toxic,potent antitubercular