title: Discovery of novel AHLs as potent antiproliferative agents.
abstract: Three series of novel AHL analogs were synthesized and evaluated for their in vitro cytotoxic activity against four human cancer cell lines. The SARs investigation indicated that AHLs with a terminal phenyl group, especially those with the chalcone scaffold had remarkably enhanced cytotoxicity than those with the hydrophobic side chains. Besides, some of these compounds were much more potent than 5-Fu and natural OdDHL. Through the detailed SARs discussions, we found that compounds 10a-k and 14 with the 4-amino chalcone scaffold showed excellent inhibition against all the tested cancer cell lines and were much more potent than 5-Fu and AHLs. Such scaffold may act as a template for further lead optimization. Compound 10i with a 3, 4, 5-trimethoxy group was the most potent one against all the tested cancer cell lines. Flow cytometry analysis indicated that analog 11e induced the cellular apoptosis and cell cycle arrest of MCF-7 cells at G2/M phase in a concentration-and time-dependent manner.
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Jing-Li
authors.initials: JL
authors.lastname: Ren
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Xu-Yao
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Xi-Xin
authors.initials: XX
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Kun-Peng
authors.initials: KP
authors.lastname: Shao
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Xiao-Ge
authors.initials: XG
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Liu
mesh_terms: D054742:Acyl-Butyrolactones / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D013329:Structure-Activity Relationship
chemical_list: D054742:Acyl-Butyrolactones; D000970:Antineoplastic Agents; D002599:Chalcone
keywords: AHLs; Apoptosis; Cell cycle arrest; Chalcones; Cytotoxicity; Dithiocarbamates