title: Cytotoxic activity, apoptosis induction and structure-activity relationship of 8-OR-2-aryl-3,4-dihydroisoquinolin-2-ium salts as promising anticancer agents.
abstract: As our continuing research, a series of 2-aryl-8-OR-3,4-dihydroisoquinolin-2-ium bromides were evaluated for cytotoxic activity on cancer cells and apoptosis induction in the present study. SAR was derived also. Among them, 23 compounds showed the higher cytotoxicity on MKN-45 cells with IC50values of 1.99-11.3μM than a standard anticancer drug cis-platinum (IC50=11.4μM) or their natural model compound chelerythrine (IC50=12.7μM); 16 compounds possessed the medium to high activity on NB4 cells with IC50values of 1.67-4.62μM. SAR analysis showed that both substitution patterns of the N-aromatic ring and the type of 8-OR significantly impact the activity. AO/EB staining and flow cytometry analysis with Annexin V/PI double staining showed that the compounds were able to induce apoptosis in a concentration-dependent manner. The results above suggested that the title compounds are a class of promising compounds for the development of new anti-cancer drugs.
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Fang-Jun
authors.initials: FJ
authors.lastname: Cao
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Zhu
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Kuang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Xing-Qiang
authors.initials: XQ
authors.lastname: Li
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Bo-Hang
authors.initials: BH
authors.lastname: Zhou
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: yxjsn2@163.com.
authors.forename: Xin-Juan
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: zhoulechem@nwsuaf.edu.cn.
authors.forename: Le
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D006041:Goats; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D012492:Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D012492:Salts
keywords: Apoptosis induction; Benzo[c]phenanthridine alkaloid; Cytotoxicity; Isoquinoline; Structure–activity relationship