New pyrazolopyridine and pyrazolothiazole-based compounds as anti-proliferative agents targeting c-Met kinase inhibition: design, synthesis, biological evaluation, and computational studies.

ABSTRACT: c-Met tyrosine kinase plays a key role in the oncogenic process. Inhibition of the c-Met has emerged as an attractive target for human cancer treatment. This work deals with the design and synthesis of a new set of derivatives bearing pyrazolo[3,4-b]pyridine, pyrazolo[3,4-b]thieno[3,2-e]pyridine, and pyrazolo[3,4-d]thiazole-5-thione scaffolds, 5a,b, 8a-f, and 10a,b, respectively, utilizing 3-methyl-1-tosyl-1H-pyrazol-5(4H)-one (1) as a key starting material. All the new compounds were evaluated as antiproliferative agents against HepG-2, MCF-7, and HCT-116 human cancer cell lines utilizing 5-fluorouracil and erlotinib as two standard drugs. Compounds 5a,b and 10a,b represented the most promising cytotoxic activity of IC₅₀ values ranging from 3.

SUBMITTER: Alamshany ZM 

PROVIDER: S-EPMC10128108 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature