Anticancer Activity of Indeno[1,2-b]-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase II alpha
- 주제(키워드) Topoisomerase II alpha , Topoisomerase catalytic inhibitor , DNA minor groove binder , Trifluoromethyl 2-(3-trifluoromethylphenyl)-4-(3-h , Halogenated 2 , 4-diphenyl Indeno[1 , 2-b]-pyridinol derivative
- 주제(기타) Biochemistry & Molecular Biology; Pharmacology & Pharmacy
- 설명문(일반) [Jeon, Kyung-Hwa; Jang, Hae Jin; Kim, Jeong-Ahn; Sheen, Naeun; Seo, Minjung; Kwon, Youngjoo] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Seoul 03760, South Korea; [Shrestha, Aarajana; Lee, Eung-Seok] Yeungnam Univ, Coll Pharm, Gyongsan 38541, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- 발행기관 KOREAN SOC APPLIED PHARMACOLOGY
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183500
- 본문언어 영어
- Published As http://dx.doi.org/10.4062/biomolther.2020.231
초록/요약
Topoisomerase II alpha has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase Ila targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase II alpha through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase II alpha, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase II alpha inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in anti-proliferative activity.
more