2. Academic Validation
  3. Secondary metabolites from Isodon ternifolius (D. Don) Kudo and their anticancer activity as DNA topoisomerase IB and Tyrosyl-DNA phosphodiesterase 1 inhibitors

Secondary metabolites from Isodon ternifolius (D. Don) Kudo and their anticancer activity as DNA topoisomerase IB and Tyrosyl-DNA phosphodiesterase 1 inhibitors

  • Bioorg Med Chem. 2020 Jun 1;28(11):115527. doi: 10.1016/j.bmc.2020.115527.
Hong-Li Zhang 1,  Yu Zhang 1,  Xue-Long Yan 1,  Long-Gao Xiao 1,  De-Xuan Hu 1,  Qian Yu 2,  Lin-Kun An 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • 2 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Clinical Pharmacy (School of Integrative Pharmacy, Institute of Integrative Pharmaceutical Research), Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: yuxi3@mail.sysu.edu.cn.
  • 3 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou 510006, China. Electronic address: lssalk@mail.sysu.edu.cn.
PMID: 32345458 DOI: 10.1016/j.bmc.2020.115527
Abstract

Based on DNA Topoisomerase IB (TOP1) and tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibition of the ethanol extract of the roots of Isodon ternifolius (D. Don) Kudo (Labiatae), its secondary metabolites has been studied. Two new compounds, an ent-abietane diterpenoid isodopene A (1) and a 2,3-seco-triterpene isodopene B (13), along with 25 known compounds were isolated. Their structures were elucidated by spectroscopic analysis and theoretical calculations. The enzyme-based assays indicated that 1 and 13 showed strong (+++) and moderate (++) TOP1 inhibition, respectively. Two chalcone derivatives 11 and 12 were firstly found as dual TDP1 and TOP1 natural inhibitors, and showed synergistic effect with the clinical TOP1 inhibitors topotecan in MCF-7 cells. Compounds 8, 16, and 22 acted as TOP1 catalytic inhibitors with equipotent TOP1 inhibition to camptothecin (++++). Compounds 7 and 8 exhibited significant cytotoxicity against MCF-7, A549, and HCT116 cells with GI50 values in the range of 2.2-4.8 μM. This work would provide valuable information that secondary metabolites from I. ternifolius could be developed as Anticancer agents.

Keywords

Cytotoxicity; DNA topoisomerase; Isodon ternifolius; Secondary metabolite; Tyrosyl–DNA phosphodiesterase.

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