Identification of novel topoisomerase II alpha inhibitors by virtual screening, molecular docking, and bioassay.
Chem Biol Drug Des
; 99(1): 92-102, 2022 01.
Article
in En
| MEDLINE
| ID: mdl-34310071
ABSTRACT
Breast cancer is one of the most common tumors, and its treatment still leaves room for improvement. Topoisomerase II alpha is a potential target for the treatment of human diseases such as breast cancer. In this article, we attempted to discover a novel anticancer drug. We have used the topoisomerase II alpha protein-Homo sapiens (Human) to hierarchically screen the Maybridge database. Based on their docking score, the top hit compounds have been assayed for inhibition in a topoisomerase II pBR322 DNA relaxation assay in vitro. Candidate compound 6 (CP6) was found to have the best inhibitory effect for topoisomerase II among the 20 tested compounds. In addition, CP6 had potent cytotoxicity against eight tested tumor cell lines. At the same time, CP6 was shown to have potential anti-multidrug resistance capabilities. This study identifies CP6, which can contribute to the development of new topoisomerase II inhibitors as anticancer agents.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Topoisomerases, Type II
/
Topoisomerase II Inhibitors
/
Molecular Docking Simulation
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Chem Biol Drug Des
Journal subject:
BIOQUIMICA
/
FARMACIA
/
FARMACOLOGIA
Year:
2022
Document type:
Article
Affiliation country:
China