Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines.
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.
Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, and Key Laboratory of Cancer Prevention and Therapy, Tianjin 30060, China. carfield@medmail.com.cn.
Ye-Hui
YH
Shi
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. dongfangshion@163.com.|High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. dongfangshion@163.com.
Dong-Fang
DF
Dai
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. zh116z@163.com.|High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. zh116z@163.com.
Jing
J
Li
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. ywdong_good@126.com.|High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. ywdong_good@126.com.
Yan-Wei
YW
Dong
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. jiangyin_001@163.com.|High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. jiangyin_001@163.com.
Yin
Y
Jiang
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. 2120151007@mail.nankai.edu.cn.|High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. 2120151007@mail.nankai.edu.cn.
Huan-Gong
HG
Li
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. icanfly0@163.com.|High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. icanfly0@163.com.
Yuan
Y
Gao
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. chongchuanke@mail.nankai.edu.cn.|High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. chongchuanke@mail.nankai.edu.cn.
Chuan-Ke
CK
Chong
High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. lihuiying130892@163.com.
Hui-Ying
HY
Li
High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. chuxiaoqian8@163.com.
Xiao-Qian
XQ
Chu
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. cyang66_2001@yahoo.com.|High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. cyang66_2001@yahoo.com.
Cheng
C
Yang
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. zhangquan@nankai.edu.cn.
Quan
Q
Zhang
Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, and Key Laboratory of Cancer Prevention and Therapy, Tianjin 30060, China. yuechen@nankai.edu.cn.
Zhong-Sheng
ZS
Tong
High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, Tianjin 300457, China. baicuigai@tjab.org.
Cui-Gai
CG
Bai
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. tongzhongsheng@tjmuch.com.
Yue
Y
Chen
D000147:Acids, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry; D061986:MCF-7 Cells; D013454:Sulfoxides
D000147:Acids, Heterocyclic; D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D000444:Aldehyde Dehydrogenase; C505407:CASP3 protein, human; D053148:Caspase 3; C016766:sulforaphane
ALDH+; KG-1a; MCF-7; SUM-159; analogues; caspase-3; sulforaphane (SFN); water soluble derivative