Design, Synthesis, Docking and Biological Study of Pyrazole-3,5-diamine Derivatives with Potent Antitubercular Activity

A new series of (E)-4-((4-substitutedphenyl)diazenyl)-1H-pyrazole-3,5-diamine derivatives were synthesized by using greener poly ethylene glycol-400 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 H37Rv strains with, pyrazinamide, isoniazid, ethambutol, and streptomycin as the standard drugs. The compounds 4a, 4b and 5a showed excellent activity while 5b exhibit moderate activity against Mycobacterium tuberculosis. Further, the molecular docking was done with an enzyme PDB:1G3U. The ligand thymidine monophosphate was completed in the crystal structure of mycobacterium tuberculosis, while Mtb Pks13 Thioesterase domain in complex with inhibitor TAM16 with PDB:5V3Y Crystal Structure showed excellent docking results. These newly synthesized derivatives of pyrazole may be useful in the development of new anti-tubercular agents.