Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 4; p. 514
• Main Authors: Shi, Ye-Hui, Dai, Dong-Fang, Li, Jing, Dong, Yan-Wei, Jiang, Yin, Li, Huan-Gong, Gao, Yuan, Chong, Chuan-Ke, Li, Hui-Ying, Chu, Xiao-Qian, Yang, Cheng, Zhang, Quan, Tong, Zhong-Sheng, Bai, Cui-Gai, Chen, Yue
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 21.04.2016; MDPI AG
• Subjects: Acids, Heterocyclic - chemical synthesis; Acids, Heterocyclic - chemistry; Acids, Heterocyclic - pharmacology; Aldehyde Dehydrogenase - metabolism; ALDH; analogues; Anticarcinogenic Agents - chemical synthesis; Anticarcinogenic Agents - chemistry; Anticarcinogenic Agents - pharmacology; Caspase 3 - metabolism; caspase-3; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Gene Expression Regulation - drug effects; Humans; Isothiocyanates - chemistry; KG-1a; MCF-7; MCF-7 Cells; sulforaphane (SFN); SUM-159; water soluble derivative; KG-1a; SUM-159; analogues; ALDH; MCF-7; sulforaphane (SFN); water soluble derivative; caspase-3
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21040514

Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH⁺ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH⁺ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX) increased the ALDH⁺ subpopulation.