Biomolecules & Therapeutics
Anticancer Activity of Indeno[1,2-b]-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα
Kyung-Hwa Jeon1, Aarajana Shrestha2, Hae Jin Jang1, Jeong-Ahn Kim1, Naeun Sheen1, Minjung Seo1, Eung-Seok Lee2,* and Youngjoo Kwon1,*
1College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760,
2College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea
*E-mail: (Lee ES), (Kwon Y)
Tel: +82-53-810-2827 (Lee ES), +82-2-3277-4653 (Kwon Y)
Fax: +82-53-810-4654 (Lee ES), +82-2-3277-3051 (Kwon Y)
Received: December 18, 2020; Revised: March 16, 2021; Accepted: April 7, 2021; Published online: May 20, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα 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 IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, 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 IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.
Keywords: Topoisomerase IIα, Topoisomerase catalytic inhibitor, DNA minor groove binder, Trifluoromethyl 2-(3-trifluoromethylphenyl)-4-(3-h, Halogenated 2,4-diphenyl Indeno[1,2-b]-pyridinol derivative

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