Secondary metabolites from Isodon ternifolius (D. Don) Kudo and their anticancer activity as DNA topoisomerase IB and Tyrosyl-DNA phosphodiesterase 1 inhibitors.
Animals
Antineoplastic Agents, Phytogenic
/ chemistry
Cattle
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
DNA Topoisomerases, Type I
/ metabolism
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Isodon
/ chemistry
Molecular Structure
Phosphodiesterase Inhibitors
/ chemistry
Phosphoric Diester Hydrolases
/ metabolism
Structure-Activity Relationship
Topoisomerase I Inhibitors
/ chemistry
Tumor Cells, Cultured
Cytotoxicity
DNA topoisomerase
Isodon ternifolius
Secondary metabolite
Tyrosyl–DNA phosphodiesterase
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
27
02
2020
revised:
17
04
2020
accepted:
20
04
2020
pubmed:
30
4
2020
medline:
2
6
2021
entrez:
30
4
2020
Statut:
ppublish
Résumé
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 GI
Identifiants
pubmed: 32345458
pii: S0968-0896(20)30353-9
doi: 10.1016/j.bmc.2020.115527
pii:
doi:
Substances chimiques
Antineoplastic Agents, Phytogenic
0
Phosphodiesterase Inhibitors
0
Topoisomerase I Inhibitors
0
Phosphoric Diester Hydrolases
EC 3.1.4.-
TDP1 protein, human
EC 3.1.4.-
DNA Topoisomerases, Type I
EC 5.99.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115527Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.