Potent Cytotoxicity of Novel L-Shaped Ortho-Quinone Analogs through Inducing Apoptosis

Abstract

Twenty-seven L-shaped ortho-quinone analogs were designed and synthesized using a one pot double-radical synthetic strategy followed by removing methyl at C-3 of the furan ring and introducing a diverse side chain at C-2 of the furan ring. The synthetic derivatives were investigated for their cytotoxicity activities against human leukemia cells K562, prostate cancer cells PC3, and melanoma cells WM9. Compounds TB1, TB3, TB4, TB6, TC1, TC3, TC5, TC9, TC11, TC12, TC14, TC15, TC16, and TC17 exhibited a better broad-spectrum cytotoxicity on three cancer cells. TB7 and TC7 selectively displayed potent inhibitory activities on leukemia cells K562 and prostate cancer cells PC3, respectively. Further studies indicated that TB3, TC1, TC3, TC7, and TC17 could significantly induce the apoptosis of PC3 cells. TC1 and TC17 significantly induced apoptosis of K562 cells. TC1, TC11, and TC14 induced significant apoptosis of WM9 cells. The structure-activity relationships evaluation showed that removing methyl at C-3 of the furan ring and introducing diverse side chains at C-2 of the furan ring is an effective strategy for improving the anticancer activity of L-shaped ortho-quinone analogs.

Recent Advances in the Synthesis of 2-Hydroxy-1,4-naphthoquinone (Lawsone) Derivatives

“…Li et al 80 conducted a study involving the synthesis of two substituted naphtho[1,2-b]furan-4,5-diones (166a-e and 167a-e) derived from lawsone (1). The synthesis involved the treatment of lawsone (1) with allyl bromide (161), followed by a subsequent Claisen rearrangement to yield 2-allyl-3-hydroxynaphthene-1,4-dione (162).…”

“…The results of the study were used to evaluate the potential of these ortho-quinone derivatives as cytotoxic agents against these specific cancer cell lines. 80…”

Tanshinone analog inhibits castration-resistant prostate cancer cell growth by inhibiting glycolysis in an AR-dependent manner

“…Besides, it has been reported that TS-IIA analogs can be used as AR inhibitors ( 14 ). TS-IIA derivative PTS33 showed the effects of AR inhibition, blocking AR-regulated gene expression, and cell growth inhibition in AR-positive PCa cells ( 15 ). Thus, TS-IIA compounds have high potential in clinical applications against PCa by targeting AR.…”