Design and synthesis of novel hydroxyanthraquinone nitrogen mustard derivatives as potential anticancer agents via a bioisostere approach.
A series of hydroxyanthraquinones having an alkylating N-mustard pharmacophore at 1'-position were synthesized via a bioisostere approach to evaluate their cytotoxicity against four tumor cell lines (MDA-MB-231, HeLa, MCF-7 and A549). These compounds displayed significant in vitro cytotoxicity against MDA-MB-231 and MCF-7 cells, reflecting the excellent selectivity for the human breast cancer. Among them, compound 5k was the most cytotoxic with IC50 value of 0.263 nM and is more potent than DXR (IC50 = 0.294 nM) in inhibiting the growth of MCF-7 cells. The excellent cytotoxicity and good selectivity of compound 5k suggest that it could be a promising lead for further design and development of anticancer agents, especially for breast cancer.
School of Chemistry and Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China. Electronic address: lmzhao@jsnu.edu.cn.
Li-Ming
LM
Zhao
School of Chemistry and Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China.
Feng-Yan
FY
Ma
School of Chemistry and Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China.
Hai-Shan
HS
Jin
RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
Shilong
S
Zheng
RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
Qiu
Q
Zhong
RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA. Electronic address: gwang@xula.edu.
Guangdi
G
Wang
D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C000608199:2-((bis(2-chloroethyl)amino)(4-fluorophenyl)methyl)-1,4-dihydroxyanthracene-9,10-dione; D000880:Anthraquinones; D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds
Anthraquinone; Antitumor activity; Nitrogen mustard; Synthesis