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

Ye-Hui Shi,Quan Zhang,Hui-Ying Li,Chuan-Ke Chong,Jing Li,Yin Jiang,Xiao-Qian Chu,Zhong-Sheng Tong,Cheng Yang,Cui-Gai Bai,Dong-Fang Dai,Huan-Gong Li,Yuan Gao,Yue Chen,Yan-Wei Dong

doi:10.3390/molecules21040514

Abstract

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.

Highlights

The natural compound, sulforaphane (SFN), was first isolated from broccoli in 1992
SFN analogues heterocyclic ring were prepared as shown in Schemes 1–4, and water soluble derivatives were prepared as shown in
The aldehyde dehydrogenase (ALDH)+ population in breast cancer cell line SUM-159 was stem cell-like cells, and it was recently reported that SFN can selectively inhibit the growth of this cell population [8]

Summary

Introduction

The natural compound, sulforaphane (SFN), was first isolated from broccoli in 1992. SFN has been found to be an effective chemo-preventive agent, and it exhibits anti-inflammatory, antioxidant, anti-proliferative and anti-cancer activities [1–7]. Sun et al reported that SFN inhibits the growth of the ALDH+ subpopulation of the breast cancer stem cell line, SUM-159, via down regulation of the Wnt/β-catenin self-renewal pathway [8]. Analogs of SFN were subsequently synthesized and their anti-cancer activities against various cancer cell lines were examined in the literature [1,4,9–19], and it was found that the replacement of the methyl group yielded compounds. A series of SFN analogues containing a heterocyclicring were synthesized, and were evaluated for their activities against the breast cancer cell lines MCF-7. SUM-159, and the leukemia stem cell-like KG-1a

Methods

Results

Conclusion