Synthesis,molecular docking,antimicrobial, antiquorum-sensing and antiproliferative activities of new series of pyrazolo[3,4-b]pyridine analogs

New series of pyrazolo3,4-b]pyridines were prepared and evaluated for antimicrobial activity toward six selected microorganisms. Compounds 2a, 3b, 3d and 3e exhibited good activity toward B. cereus. On the other hand, 2a and 3b evinced interesting activity over C. albicans, whereas 2a, 3b and 3e displayed promising activity over A. fumigatus. Antiquorum-sensing effectiveness of the new members over C. violaceum was also assessed, where compounds 2a and 3b exhibited higher activity than that of the reference compound, indole. In vitro antiproliferative assessment toward HepG2, HCT-116 and MCF-7 cancer cells evidenced that 2f has notable effectiveness on all examined cell lines, whereas 3a–c were active but to a lower extent. In vivo antitumor activity of 2f and 3a–c against EAC cells was also esteemed, where 2f and 3c showed considerable activity comparable to that of doxorubicin. Cytotoxicity screening over WI38 and WISH normal cells evinced that 2f and 3a–c are less cytotoxic than doxorubicin. Compounds 2a, 2f, 3a–c and 3e were evaluated for DNA-binding affinity and topoisomerase IIβ inhibitory activity. Analogs 2a, 2f, 3a and 3b illustrated strong DNA-binding affinity, whereas 2a, 2f and 3a exhibited interesting topoisomerase IIβ inhibitory activity. Compounds 2a and 2f were docked into topoisomerase IIβ, where 2f showed preferential binding to topoisomerase IIβ. Computational studies articulated that the new members are in compliance with Veber's standards and Lipinski’s rule.