Author:
Yu Ling,Li Jian-hui,Zhu Ju,Wang You-de,Yan Zhi-wei,Zhang Li-ying,Li Shuai
Abstract
AbstractAs an essential marker of cancer treatment, PARP-1 inhibitors could effectively kill tumor cells through a mechanism known as synthetic lethality and are used to treat a variety of cancers. In order to explore novel PARP-1 inhibitors, a series of 22 novel erythrina derivatives were reported and preliminarily explored their mechanism of action. The antitumor activities against four human cancer cell lines including A549, OVCAR-3, HCT-116, and MCF-7 were evaluated, and the preliminary SARs were summarized. Among them, compound 11b exhibited better anti-proliferative effects against A549 cells (IC50 = 1.95 µM). The SI results showed that compound 11b had low toxicity. Moreover, compound 11b displayed excellent PARP-1 inhibitory activities with IC50 values of 19.24 nM. In addition, molecular docking studies provided the rational binding modes of compound 11b in complexes with PARP-1. The flow cytometry assays revealed that compound 11b could induce apoptosis of A549 cells (P < 0.001). Simultaneously, compound 11b could effectively reduce the formation of PAR (P < 0.001). The ADMET prediction results indicated compound 11b had similar properties to rucaparib. Collectively, compound 11b has potential research value for further investigation.
Funder
National Natural Science Foundation of China
the Biological Medicine Joint Fund of Natural Science Foundation of Hebei Province
the Funded by Science and Technology Project of Hebei Education Department
the 2022 Research Start‐up Fund for High‐level Talents of Chengde Medical University
the Chengde Medical University basic research funds special project
Publisher
Springer Science and Business Media LLC