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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Rapid Screening of Active Components with Topoisomerase I Inhibitory Activity in Sophora alopecuroides L. Based on Ultrafiltration Coupled with UPLC-QTOF-MS

Author(s): Lin Zhang, Xiaoying Yin*, Xi Wan, Yun Sun, Menghui Cao and Sheng Ouyang

Volume 23, Issue 7, 2022

Published on: 11 August, 2021

Page: [998 - 1008] Pages: 11

DOI: 10.2174/1389201022666210602105609

Price: $65

Abstract

Background: Topoisomerase I (Topo I) is a key target of many antitumor drugs in vivo. Alkaloids in Sophora alopecuroides L. can reportedly inhibit Topo I activity, but the pharmacodynamic material basis has not yet been determined.

Objective: This study aimed to rapidly identify active components which inhibit Topo I in S. alopecuroides L.

Methods: Affinity ultrafiltration coupled with ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UF-UPLC-QTOF-MS) screening system based on Topo I protein was established to screen and isolate a total alkaloid fraction in S. alopecuroides L. Topo I inhibitory activity and anti-tumor proliferation activity of the screened components were evaluated, and their molecular mechanisms were studied.

Results: Six compounds that bound specifically to Topo I were obtained. Further screening showed that matrine, cytisine, and sophoridine presented higher inhibitory activity on Topo I and were able to inhibit the proliferation of breast cancer MDA-MB-468 cells with IC50 values of 9.40 ± 1.12 mM, 17.4 ± 2.20 mM, and 10.4 ± 1.37 mM, respectively. To the best of our knowledge, their dual molecular mechanisms against Topo I have not discussed to date. In this study, the following dual mechanisms are reviewed for the first time: (1) stabilization of the Topo I-DNA complex and (2) inhibition or blocking of Topo I binding to DNA.

Conclusion: Matrine, cytisine, and sophoridine from S. alopecuroides L. were defined as the active components possessing Topo I inhibitory activity, and their pharmacological mechanism was confirmed, which provided an important base for further research and development of antitumor components from S. alopecuroides L.

Keywords: Sophora alopecuroides L., topoisomerase I inhibitory avtivity, UF-UPLC-QTOF-MS, active components group, molecular mechanisms, effective substances.

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