Copper-Catalyzed Syntheses of Pyrene-Pyrazole Pharmacophores and Structure Activity Studies for Tubulin Polymerization.

ABSTRACT: Tubulin polymerization is critical in mitosis process, which regulates uncontrolled cell divisions. Here, we report a new class of pyrene-pyrazole pharmacophore (PPP) for targeting microtubules. Syntheses of seven pyrenyl-substituted pyrazoles with side-chain modification at N-1 and C-3 positions of the pyrazole ring were accomplished from alkenyl hydrazones via C-N dehydrogenative cross-coupling using copper catalyst under aerobic condition. Tubulin polymerization with PPPs was investigated using docking and biological tools to reveal that these ligands are capable of influencing microtubule polymerization and their interaction with α-, β-tubulin active binding sites, which are substituent specific. Furthermore, cytotoxicity response of these PPPs was tested on cancer cells of different o

SUBMITTER: Sar D 

PROVIDER: S-EPMC6130796 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature