Design, Synthesis, Toxicity Estimation and Molecular Docking Studies of N-(furan-2-yl)-1-(5-substituted) phenyl-1,3,4-oxadiazol-2-yl) methanimine as Antitubercular Agents

B Mathew; J Suresh; Githa E Mathew; George Sonia; G K Krishnan

Design, Synthesis, Toxicity Estimation and Molecular Docking Studies of N-(furan-2-yl)-1-(5-substituted) phenyl-1,3,4-oxadiazol-2-yl) methanimine as Antitubercular Agents

Indian J Pharm Sci. 2014 Sep;76(5):401-6.

Authors

B Mathew¹, J Suresh², Githa E Mathew¹, George Sonia³, G K Krishnan⁴

Affiliations

¹ Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Grace College of Pharmacy, Palakkad-678 004, India.
² Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College Chennai-600 003, India.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, SRIPS, Coimbatore-641 044, India.
⁴ Department of Pharmaceutical Chemistry, College of Pharmaceutical Science, Govt. Medical College, Trivandrum-695 011, India.

PMID: 25425753
PMCID: PMC4243256

Abstract

A series of novel N-(furan-2-yl)-1-(5-substituted) phenyl-1,3,4-oxadiazol-2-yl) methanimines (Fa-e) were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (H37Rv) strain by using alamar blue assay. The synthesized compounds were characterized based on IR, (1)HMR and mass spectral analysis. The toxicity profile was predicted by organic chemistry portal, a web based application for predicting in silico absorption, distribution, metabolism, excretion and toxicity, and the novel derivatives under study did not show any toxicity issues. The mechanism of action of the titled derivatives was predicted by docking on the Mycobacterium tuberculosis Enoyl-ACP reductase enzyme. The docking study concluded that Fb and Fa possessed good binding energy indicating more prominent interaction towards the active sites NAD and TYR 158. The antitubercular studies showed that the both Fa and Fb possessed significant activity with the MIC as low as 3.125 μg/ml.

Keywords: 1,3,4-oxadiazole; Enoyl-ACP reductase; in silico ADMET; molecular docking.