title: Synthesis and biological evaluation of novel farnesylthiosalicylic acid derivatives for cancer treatment.
abstract: Novel farnesylthiosalicylic acid (FTS) derivatives were synthesized by coupling with different substituted diamines. Their in vitro growth inhibitory activities against seven human cancer cell lines were evaluated. The results revealed that the synthetic farnesylthiosalicylamides displayed significant antitumor activities compared to the positive control FTS. Especially, compound 8f exhibited the strongest antitumor activities with IC50 values of 6.20-7.83 µM, which were one- to threefold less than those of sorafenib and six- to tenfold less than that of FTS against each cell line in vitro. Furthermore, 8f could inhibit the Ras-related signaling pathway and induce SMMC-7721 cell apoptosis superior to FTS in a dose-dependent manner. These data indicate that 8f may hold greater promise as therapeutic agent for the intervention of human cancers.
authors.affiliation: School of Pharmacy, Nantong University, Nantong, P. R. China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ling
authors.forename: Xuemin
authors.initials: X
authors.lastname: Wang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Chenjun
authors.initials: C
authors.lastname: Xu
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005204:Farnesol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015394:Molecular Structure; D012459:Salicylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol; D018631:ras Proteins
keywords: Antitumor activity; Diamines; Farnesylthiosalicylic acid; Ras-related signal pathway; Synthesis