A Chalcone Annulated Pyrazoline Conjugates as a Potent Antimycobacterial Agents: Synthesis and in Silico Molecular Modeling Studies

Abstract

Pyrazolines are well known and important nitrogen containing 5-membered heterocyclic compounds could effective against diversity of biological issue in which the tuberculosis is one of them. An effort was made to design and synthesis the series of chalcone annulated pyrazoline conjugates as a target candidate for antimycobacterial activity against Mycobacterium tuberculosis. The synthesized compounds were subjected to characterization by diverse analytical methods and to foreword in silico screening study for testing their antimycobacterial activity via their docking simulation on bioinformatics software, Molecular Operating Environment 2009.10. suite. The wonderful number of interactions with active site residues coupled with favorable binding energy state that these target molecules may serve as an effective replacement agent for the antimycobacterial drugs. The preliminary SAR of the chalcone annulated pyrazoline conjugates reveals that compounds possessing electron withdrawing groups such as halogen atom (P1, P2) in its structure favors better activity and anchored tightly inside the active site canyon (Site I) of the protein. It is also observed that the presence of methoxy and dimethylamino substitutions at aromatic ring (P3, P4 & P7) doesn t seem to influence the activity, this is may be due to its high electro negativity and the presence of lone pair of electron with this substitutions. Thus, the synthesized chalcone annulated pyrazoline conjugates might serve as the best drug candidate for the existence menacing pathogen Mycobacterium tuberculosis. The predictive model can be employed further for virtual screening of new compounds in this series.