A new series of 2-phenol-4-aryl-6-chlorophenyl pyridine derivatives as dual topoisomerase I/II inhibitors: Synthesis, biological evaluation and 3D-QSAR study
- 주제(키워드) 2-phenol-4-aryl-6-chlorophenyl pyridine , 3D-QSAR , Antitumor agents , CoMFA , Cytotoxicity , Dual topoisomerase I and II inhibition
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier Masson SAS
- 발행년도 2016
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000125469
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.ejmech.2016.02.050
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
As a continuous effort to develop novel antitumor agents, a new series of forty-five 2-phenol-4-aryl-6-chlorophenyl pyridine compounds were synthesized and evaluated for cytotoxicity against four different human cancer cell lines (DU145, HCT15, T47D, and HeLa), and topoisomerase I and II inhibitory activity. Several compounds (10-15, 20, 22, 24, 28, 42, and 49) displayed strong to moderate dual topoisomerase I and II inhibitory activity at 100 μM. It was observed that hydroxyl and chlorine moiety at meta or para position of phenyl ring is favorable for dual topoisomerase inhibitory activity and cytotoxicity. Most of the compounds displayed stronger cytotoxicities than those of all positive controls against the HCT15 and T47D cell lines. For investigation of the structure-activity relationships, a 3D-QSAR analysis using the method of comparative molecular field analysis (CoMFA) was performed. The generated 3D contour maps can be used for further rational design of novel terpyridine derivatives as highly selective and potent cytotoxic agents. © 2016 Elsevier Masson SAS. All rights reserved.
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