Exploring the Anti-Cancer Mechanism of Novel 3,4'-Substituted Diaryl Guanidinium Derivatives.

ABSTRACT: We previously identified a guanidinium-based lead compound that inhibited BRAF through a hypothetic type-III allosteric mechanism. Considering the pharmacophore identified in this lead compound (i.e., "lipophilic group", "di-substituted guanidine", "phenylguanidine polar end"), several modifications were investigated to improve its cytotoxicity in different cancer cell lines. Thus, several lipophilic groups were explored, the di-substituted guanidine was replaced by a secondary amine and the phenyl ring in the polar end was substituted by a pyridine. In a structure-based design approach, four representative derivatives were docked into an in-house model of an active triphosphate-containing BRAF protein, and the interactions established were analysed. Based on these com

SUBMITTER: Previtali V 

PROVIDER: S-EPMC7767381 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature