ADMET PREDICTIONS, PHARMACOKINETICS AND IN-SILICO MOLECULAR DOCKING SIMULATION STUDIES OF CARBOXAMIDE DERIVATIVES AS ANTI-TUBERCULAR AGENTS

Shruti Y.*, Prabhudev S.M., Dr. Channamma M., Dr. Kishore Singh C. and Hanamanth J.K.

ABSTRACT

Molecular docking simulation of 6 molecules of N-(2-phenoxy) ethyl imidazo [1, 2-a] pyridine-3-carboxamide (IPA) with Mycobacterium tuberculosis target (DNA gyrase) was carried out so as to evaluate their theoretical binding affinities. The docking operation was carried out using PyRx virtual screening software. Molecule SY1-6 with the highest binding affinity of − 7.2 kcal/mol was selected as the lead molecule for structural modification which led to the development of four newly hypothetical molecules S1, S2, S3 and S4. In addition, the S4 molecule with the highest binding affinity value of − 9.4 kcal/mol formed more H-bond interactions signifying better orientation of the ligand in the binding site compared to SY6 and Isoniazid standard drug. In-silico ADMET and drug-likeness prediction of the molecules showed good pharmacokinetic properties having high gastrointestinal absorption, orally bioavailable, and less toxic.

Keywords: Molecular docking simulation, Pharmacokinetics, ADMET & drug-likeness prediction, Molecular Interactions.