title: Synthesis and bio-evaluation of novel quinolino-stilbene derivatives as potential anticancer agents.
abstract: A series of 25 novel quinolino-stilbene derivatives were designed, synthesized and evaluated for their potential as anticancer agents. Three of them not only displayed quite potent antiproliferative activity with IC50 values<4μM but also showed approximately twofold selectivity against cancer cells, compared to non-cancerous cells. Three other compounds exhibited comparatively good activity with IC50 values in the range of 4-10μM, and the rest was moderately active or inactive. One of these viz. 3-[E-(4-fluorostyryl)]-2-chloroquinoline (compound 7B) caused substantial DNA damage and arrested cell cycle in S phase. Interestingly, 7B was very active against MDA-MB468 (IC50=0.12μM), but not against other cell lines examined. Compound 3-[Z-(3-(trifluoromethyl)styryl)]-2-chloroquinoline (12A), the most effective against all cancer cell lines examined, caused prolonged cell cycle arrest at mitosis and eventually apoptosis. Data from an in vitro study showed that compound 12A inhibited microtubule polymerization in a similar fashion to nocodazole. Further study using in silico molecular modeling revealed that 12A causes the impediment of microtubule polymerization by binding to tubulin at the same cavity where podophyllotoxin binds.
authors.affiliation: Advanced Medical Research Institute of Canada, Health Sciences North, 41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada; Division of Medical Sciences, Northern Ontario School of Medicine, 935 Ramsey Lake Road, Sudbury, Ontario P3E 2C6, Canada.
authors.forename: Vandana
authors.initials: V
authors.lastname: Srivastava
authors.affiliation: Advanced Medical Research Institute of Canada, Health Sciences North, 41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada; Division of Medical Sciences, Northern Ontario School of Medicine, 935 Ramsey Lake Road, Sudbury, Ontario P3E 2C6, Canada; Department of Medicine, The University of Ottawa, Ottawa, Ontario K1H 5M8, Canada. Electronic address: hlee@amric.ca.
authors.forename: Hoyun
authors.initials: H
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators
keywords: Anticancer agent; Apoptosis; Cell cycle; Quinoline; Spindle checkpoint; Stilbene; Tubulin