Potent Cytotoxicity of Novel L-Shaped Ortho-Quinone Analogs through Inducing Apoptosis.
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.
['Li|Sheng-You|SY|', 'Sun|Ze-Kun|ZK|', 'Zeng|Xue-Yi|XY|', 'Zhang|Yue|Y|', 'Wang|Meng-Ling|ML|', 'Hu|Sheng-Cao|SC|', 'Song|Jun-Rong|JR|', 'Luo|Jun|J|', 'Chen|Chao|C|0000-0002-0378-0589', 'Luo|Heng|H|', 'Pan|Wei-Dong|WD|']
D000970:Antineoplastic Agents D017209:Apoptosis D045744:Cell Line, Tumor D049109:Cell Proliferation D003603:Cytotoxins D004354:Drug Screening Assays, Antitumor D006801:Humans D020014:K562 Cells D009369:Neoplasms D000078722:PC-3 Cells D011809:Quinones D013329:Structure-Activity Relationship
ortho-quinones antitumor activity beta-lapachone tanshione IIA