AUTHOR=Wan Minghui , Zhang Lei , Chen Yiming , Li Qiang , Fan Wenli , Xue Qingxia , Yan Fang , Song Weiguo 

TITLE=Synthesis and Anticancer Activity Evaluation of Novel Phenanthridine Derivatives

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00274

DOI=10.3389/fonc.2019.00274

ISSN=2234-943X

ABSTRACT=<p>Based on the structure of sanguinarine, fourteen phenanthridine derivatives were designed and synthesized in the current study. The cytotoxic activities of synthesized compounds were evaluated against five human cancer cell lines (MCF-7, PC3, Hela, A549, and HepG2 cell lines) via MTT assay. Among all the compounds tested, molecule <bold>8a</bold> exhibited significant cytotoxic activity against MCF-7 cells with a IC<sub>50</sub> value of 0.28 μM. A following up enzymatic assay indicated that compound <bold>8a</bold> could inhibit the activity of DNA topoisomerase I/II. Further mechanistic studies performed in the MCF-7 cell line revealed that compound <bold>8a</bold> could arrest cell cycle in S phase and induce cell apoptosis via downregulation of Bcl-2 and upregulation of Bax. Collectively, a potent DNA topoisomerase inhibitor (<bold>8a</bold>) was discovered, which exhibited potential as a candidate chemotherapeutic agent for the management of tumors in the present study.</p>