A new phenolic series of indenopyridinone as topoisomerase inhibitors: Design, synthesis, and structure-activity relationships
- 주제(키워드) Indenopyridinone , Phenolic group , Topoisomerase inhibitor , DNA intercalator , Anti-proliferative activity
- 주제(기타) Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic
- 설명문(일반) [Shrestha, Aarajana; Katila, Pramila; Shrestha, Ritina; Lee, Eung-Seok] Yeungnam Univ, Coll Pharm, Gyongsan 712749, South Korea; [Park, Seojeong; Jang, Hae Jin; Kwon, Youngjoo] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Ewha Global Top Program 5, Seoul 120750, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 PERGAMON-ELSEVIER SCIENCE LTD
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156169
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bmc.2018.09.021
초록/요약
DNA Topoisomerase II alpha (topo II alpha) is one of the most effective therapeutic targets to control cancer. In an effort to develop novel and effective topo II alpha targeting anti-proliferative agent, a phenolic series of indenopyridinone and indenopyridinol were designed and prepared using efficient multi-component one pot synthetic method. Total twenty-two synthesized compounds were assessed for topo I and II alpha inhibition, and anti-proliferation in three different human cancer cell lines. Overall structure-activity relationship study explored the significance of meta-phenolic group at 4-position and para-phenolic group at 2- and/or 4-position of indenopyridinone skeleton for strong topo II alpha-selective inhibition and anti-proliferative activity against human cervix (HeLa) and colorectal (HCT15) cell lines. Compound 12 with excellent topo II alpha inhibition (93.7%) was confirmed as a DNA intercalator that could be a new promising lead to develop effective topo II alpha-targeted anticancer agents.
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