Fluorescein hydrazones: A series of novel non-intercalative topoisomerase IIα catalytic inhibitors induce G1 arrest and apoptosis in breast and colon cancer cells
- 주제(키워드) Apoptosis , Fluorescein , Fluorescein hydrazones , Topoisomerase IIα catalytic inhibitor
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier Masson SAS
- 발행년도 2017
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000139373
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.ejmech.2016.09.004
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Fluorescein hydrazones (5 and 7) were synthesized in three/four steps with 82–92% yields. All synthesized compounds were evaluated by topoisomerase I (topo I) and topoisomerase IIα (topo IIα)-mediated relaxation and cell viability assays. Among them, most of the compounds showed topo I & IIα inhibitory activity and nineteen compounds showed strong anti-proliferative activity against various cell lines. In brief, 5e inhibited 53% topo IIα (etoposide 29%) at 20 μM and showed excellent antiproliferative activity against DU145 (1.43 ± 0.04 μM), HCT15 (2.4 ± 0.03 μM) and MCF7 (11.4 ± 0.5 μM) cell lines in comparison with adriamycin, etoposide, and camptothecin. Compounds 5e, 5g and 5h were further evaluated to determine their mode of action. Compounds 5e, 5g and 5h functioned as non-intercalative topo IIα catalytic inhibitor with induction of G1 arrest and activation of apoptotic proteins in dose-dependent manner. © 2016 Elsevier Masson SAS
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