Synthesis and antitumor activity of novel hybrid compounds between 1, 4‐benzodioxane and imidazolium salts. Issue 10 (8th June 2022)

• Record Type: Journal Article
• Authors: Liu, Zhengfen; Zhang, Yaguan; Dong, Jianwei; Fang, Yongsheng; Jiang, Yonggang; Yang, Xiaodong; Cheng, Feixiang
• Is Part Of: Archiv der Pharmazie. Volume 355:Issue 10(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-08
• Subjects: 1, 4‐benzodioxane -- biological evaluation -- cytotoxic activity -- imidazolium salts -- structure–activity relationship; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202200109
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: A series of novel hybrid compounds between 1, 4‐benzodioxane and imidazolium salts was designed and prepared. The compounds were evaluated in vitro against a panel of human tumor cell lines (K562, SMMC‐7721, and A‐549). The structure–activity relationship results demonstrated that the 2‐methyl‐benzimidazole or 5, 6‐dimethyl‐benzimidazole ring and substitution of the imidazolyl‐3‐position with a 4‐phenylphenacyl substituent were critical for promoting cytotoxic activity. Particularly, compound 25 was found to be the most potent compound with IC50 values of 1.06–8.31 μM against the three human tumor cell lines and exhibited higher selectivity to K562 and SMMC‐7721 cells with IC50 values 4.5‐ and 4.7‐fold lower than cisplatin. Moreover, compound 25 inhibited cell proliferation by inducing the G0/G1 cell cycle arrest and apoptosis in SMMC‐7721 cells. Abstract : The designed and synthesized 1, 4‐benzodioxane imidazolium salts derivative 25 was found to be the most potent compound, with IC50 values of 1.06–8.31 μM against three human tumor cell lines (K562, SMMC‐7721, and A‐549), and exhibited higher selectivity to K562 and SMMC‐7721 cells than cisplatin. Compound 25 inhibited cell proliferation by inducing the G0/G1 cell cycle arrest and apoptosis in SMMC‐7721 cells.