Design, Synthesis, and Anticancer Activity of Novel Trimethoxyphenyl-Derived Chalcone-Benzimidazolium Salts

Jun-Li Yang; Yong-Hui Ma; Yan-Hua Li; Yi-Peng Zhang; Hong-Chang Tian; Yuan-Cheng Huang; Yan Li; Wen Chen; Li-Juan Yang

doi:10.1021/acsomega.9b03077

Design, Synthesis, and Anticancer Activity of Novel Trimethoxyphenyl-Derived Chalcone-Benzimidazolium Salts

ACS Omega. 2019 Nov 20;4(23):20381-20393. doi: 10.1021/acsomega.9b03077. eCollection 2019 Dec 3.

Authors

Jun-Li Yang^{1

2}, Yong-Hui Ma¹, Yan-Hua Li², Yi-Peng Zhang¹, Hong-Chang Tian¹, Yuan-Cheng Huang¹, Yan Li³, Wen Chen¹, Li-Juan Yang²

Affiliations

¹ Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. China.
² School of Chemistry & Environment, Engineering Research Center for Green Preparation Technology of Biobased Materials, Yunnan Minzu University, Kunming 650500, P. R. China.
³ State Key Laboratory for Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650204, P. R. China.

Abstract

A series of novel trimethoxyphenyl-derived chalcone-benzimidazolium salts were synthesized. The biological properties of the compounds were screened in vitro against five different human tumor cell lines. The results suggest that the 5,6-dimethyl-benzimidazole or 2-methyl-benzimidazole ring as well as the 2-naphthylmethyl, 4-methylbenzyl, or 2-naphthylacyl substituent at position-3 of the benzimidazole ring was important to the cytotoxic activity. Notably, (E)-5,6-dimethyl-3-(naphthalen-2-ylmethyl)-1-(3-(4-(3-(3,4,5-trimethoxyphenyl)acryloyl)phenoxy)propyl)-1H-benzo[d]imidazol-3-ium bromide (7f) was more selective to HL-60, MCF-7, and SW-480 cell lines with IC₅₀ values 8.0-, 11.1-, and 5.8-fold lower than DDP. Studies of the antitumor mechanism of action showed that compound 7f could induce cell-cycle G1 phase arrest and apoptosis in SMMC-7721 cells.