Antitumor Agents. 250. Design and Synthesis of New Curcumin Analogues as Potential Anti-Prostate Cancer Agents

Abstract

In a continuing study of curcumin analogues as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogues classified into four series: monophenyl analogues (series A), heterocycle-containing analogues (series B), analogues bearing various substituents on the phenyl rings (series C), and analogues with various linkers (series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells, seven only against LNCaP, and one solely against PC-3. This study established an advanced structure-activity relationship (SAR), and these correlations will guide the further design of new curcumin analogues with better anti-prostate cancer activity.

Kurkumin ve analoglarının antikanserojen etkileri

“…Kurkumin; osteoblastik ve osteoklastik hücre bileşenleri ile prostat kanser hücreleri arasındaki büyüme faktörü işbirliğini engeller [47]. Diasetildemetoksikurkumin, triasetildemetilkurkumin ve 4-etoksikarboniletil kurkumin gibi bazı kurkumin türevlerinin; prostat kanserine karşı kurkuminden daha etkili olduğu bulunmuştur [49][50].…”

Perspectives on New Synthetic Curcumin Analogs and their Potential Anticancer Properties

“…Lin et al [81] have designed 4-fluoro-4-ethoxycarbonylethyl curcumin (83) and 4-ethoxycarbonylethylenyl curcumin (84) to overcome the problems inherent in the tautomerism of 4-Ethoxycarbonylethyl curcumin (ECECur) (82). These compounds and their synthetic intermediates (including compound 85) were evaluated for their inhibitory activity against LNCaP and PC-3 prostate cancer cell lines at a concentration of 3 M. While the keto-enol analogs showed varying anti-androgen potencies, the diketo compounds showed no activity.…”

“…Among them, compound 86 was found to be the most potent antiandrogenic agent and is considered to be a promising drug candidate for the treatment of prostate cancer. Lin et al [82] have synthesized further curcumin analogs containing monophenyl and substituted phenyl/heterocyclic moieties at the methylenic position of curcumin with various linkers. These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, viz.…”

Synthesis and Cytotoxic Evaluation of Monocarbonyl Analogs of Curcumin as Potential Anti‐Tumor Agents

“…Substituents on the 4/4′‐position of curcumin may represent an important pharmacophore for biological activity [Ohtsu et al, 2002; Lin et al, 2006a, 2006b; Quincoces Suarez et al, 2010]. The curcumin analog ASC‐J9, which has a methoxy group at the 4/4′‐position had enhanced anti‐androgenic activity and cytotoxicity against prostate cancer cell lines [Lin et al, 2006a, 2006b; Shi et al, 2009].…”

“…The curcumin analog ASC‐J9, which has a methoxy group at the 4/4′‐position had enhanced anti‐androgenic activity and cytotoxicity against prostate cancer cell lines [Lin et al, 2006a, 2006b; Shi et al, 2009]. …”