A new phenolic series of indenopyridinone as topoisomerase inhibitors: Design, synthesis, and structure-activity relationships
- Bioorg Med Chem. 2018 Oct 1;26(18):5212-5223. doi: 10.1016/j.bmc.2018.09.021.
- 1. College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
- 2. College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
- 3. College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: [email protected].
- 4. College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: [email protected].
DNA Topoisomerase IIα (topo IIα) is one of the most effective therapeutic targets to control Cancer. In an effort to develop novel and effective topo IIα 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 IIα 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 IIα-selective inhibition and anti-proliferative activity against human cervix (HeLa) and colorectal (HCT15) cell lines. Compound 12 with excellent topo IIα inhibition (93.7%) was confirmed as a DNA intercalator that could be a new promising lead to develop effective topo IIα-targeted Anticancer agents.