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

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ACS Omega. 2021 Feb 9;6(7):4842-4849. doi: 10.1021/acsomega.0c05822. eCollection 2021 Feb 23.


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 prometaphase and metaphase followed by induction of sub-G1 accumulation. Thus, 2 and 3 have good potential as leads for continued development of treatments for cancers especially for not only androgen-independent PCa but also multidrug-resistant tumors.

PMID:33644592 | PMC:PMC7905931 | DOI:10.1021/acsomega.0c05822