Cyanopyridinone- and Cyanopyridine-Based Cancer Cell Pim-1 Inhibitors: Design, Synthesis, Radiolabeling, Biodistribution, and Molecular Modeling Simulation.

ABSTRACT: In this study, two new series of 3-cyanopyridinones (3a-e) and 3-cyanopyridines (4a-e) were synthesized and evaluated for their cytotoxicity and Pim-1 kinase inhibitory activity adopting 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and in vitro Pim-1 kinase inhibition assay, respectively. Most of the tested compounds revealed promising cytotoxicity against HepG-2, HCT-116, MCF-7, and PC-3 cell lines. Among them, compounds 4c and 4d showed more potent cytotoxicity against the HePG2 cell line with IC₅₀ = 8.02 ± 0.38 and 6.95 ± 0.34 μM, respectively, than that of the reference 5-FU (IC₅₀ = 9.42 ± 0.46 μM). Moreover, compound 4c was more potent against HCT-116 (IC₅₀ = 7.15 ± 0.35 μM) than 5-

SUBMITTER: Mansour B 

PROVIDER: S-EPMC10249106 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature