Design, Synthesis, Docking and Biological Study of Pyrazole-۳,۵-diamine Derivatives with Potent Antitubercular Activity

A new series of (E)-۴-((۴-substitutedphenyl)diazenyl)-۱H-pyrazole-۳,۵-diamine derivatives were synthesized by using greener poly ethylene glycol-۴۰۰ as a reaction solvent. The drug resistance capacity and growing incidence of Mycobacterium tuberculosis infections have been increasing day by day. There is high demand for the synthesis of multidrug resistance anti-tubercular drugs. Herein, all the newly prepared ligand was subjected to the Vitro anti-tubercular activity against Mycobacterium tuberculosis against H۳۷Rv strains with, pyrazinamide, isoniazid, ethambutol, and streptomycin as the standard drugs. The compounds ۴a, ۴b and ۵a showed excellent activity while ۵b exhibit moderate activity against Mycobacterium tuberculosis. Further, the molecular docking was done with an enzyme PDB:۱G۳U. The ligand thymidine monophosphate was completed in the crystal structure of mycobacterium tuberculosis, while Mtb Pks۱۳ Thioesterase domain in complex with inhibitor TAM۱۶ with PDB:۵V۳Y Crystal Structure showed excellent docking results. These newly synthesized derivatives of pyrazole may be useful in the development of new anti-tubercular agents.

Keywords:

Mycobacterium Tuberculosis , Pyrazole derivatives , PEG-۴۰۰