Design, synthesis, molecular docking, and biological activity of pyrazolo[3,4- b ]pyridines as promising lead candidates against Mycobacterium tuberculosis

Pyrazolo[3,4- b ]pyridine is a medicinally privileged structure. We have achieved a new and facile synthesis of a combinatorial library of its tetra- and persubstituted derivatives by trifluoracetic acid catalyzed condensation of a group of 5-aminopyrazoles and a group of α-oxoketene dithioacetals. Furthermore, we demonstrated structural modification of the products via reductive desulfurization, hydrolysis of the ester, and Suzuki coupling of the bromo derivative with aryl boronic acids. Some products were subjected to in vitro Microplate Alamar Blue assay (MABA) assay against M. tuberculosis H37Rv strain and in silico analysis by binding to Pantothenate Synthetase from M. tuberculosis (MTBPS). The results indicated that the pyazolo[3,4- b ]pyridine with N(1)CH 3 , C(3)C 6 H 5 , C(4) p CH 3 C 6 H 5 , C(5)CO 2 Et, C(6)SMe substitutions exhibits promising antituberculotic activity.