Bicyclic Chalcones as Mitotic Inhibitors for Overcoming Androgen Receptor-Independent and Multidrug-Resistant Prostate Cancer.

ABSTRACT: To improve the biological effects of the lead compound 5'-chloro-2,2'-dihydroxychalcone (Cl-DHC), bicyclic aromatic chalcones were designed, synthesized, and evaluated against androgen-independent prostate cancer (PCa) DU145 and PC-3 cell proliferation. Newly synthesized bi-naphthyl derivatives 2 and 3 suppressed the proliferation of these two cell lines and also taxane-resistant prostate cancer cell lines at a submicromolar level. The two compounds were 4-18 times more potent than the parent molecule Cl-DHC. A structure-activity relationship analysis revealed that the orientation of the 10π-electron ring-A naphthalene had a significant effect on the activity. Mode-of-action studies in KB-VIN cells demonstrated that 2 and 3 arrested cells in mitosis at prometaph

SUBMITTER: Saito Y 

PROVIDER: S-EPMC7905931 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature