title: A new chiral 2-(ethylthio)-thiazolone analogue shows strong antitumor activities by inducing cancer cell apoptosis and inhibiting angiogenesis.
abstract: Our initial study showed the potent cytotoxic effects of a series of new chiral 2-(ethylthio)-thiazolone analogues we synthesized. In the present study, we used computer prediction and found that nitro functionality and the modification of substituents R could further improve their activities in the presence of the nitro group. Compound 1s with nitro, naphthyl, ethyl groups, and a chiral center was predicted to be the most effective. We showed that compound 1s could inhibit the growth of five different cancer cell lines in a time-dependent and dose-dependent manner. 1s could induce Hela cell apoptosis by activating the mitochondria apoptotic pathway. In addition, 1s could inhibit the proliferation, migration, tuber formation, and adhesion of human umbilical vein endothelial cells, suggesting its antiangiogenesis effects. Furthermore, we confirmed the in-vivo antitumor effects of 1s on sarcoma S-180-bearing mice. Taken together, chiral 2-(ethylthio)-thiazolone analogue 1s is a promising compound for further anticancer drug development.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, People's Republic of China.
authors.forename: Hongjin
authors.initials: H
authors.lastname: Song
authors.forename: Ming
authors.initials: M
authors.lastname: Kai
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Yin
authors.forename: Qian
authors.initials: Q
authors.lastname: Zeng
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yao
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D013844:Thiazoles