title: Synthesis and biological evaluation of farnesylthiosalicylamides as potential anti-tumor agents.
abstract: Fourteen hybrids of farnesylthiosalicylic acid (FTS) with various diamines were synthesized and biologically evaluated. It was found that FTS-monoamide molecules (10a-g) displayed strong anti-proliferative activity against seven human cancer cell lines, superior to FTS and FTS-bisamide compounds (11a-g). The mono-amide 10f was the most active, with IC₅₀s of 3.78-7.63 μM against all tested cancer cells, even more potent than sorafenib (9.12-22.9 μM). In addition, 10f induced SMMC-7721 cell apoptosis, down-regulated the expression of Bcl-2 and up-regulated Bax and caspase-3. Furthermore, 10f had the improved aqueous solubility relative to FTS. Finally, treatment with 10f dose-dependently inhibited the Ras-related signaling pathways in SMMC-7721 cells. Collectively, 10f could be a promising candidate for the intervention of human cancers.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Medical College, Nantong University, Nantong 226001, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ling
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Medical College, Nantong University, Nantong 226001, PR China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Medical College, Nantong University, Nantong 226001, PR China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Medical College, Nantong University, Nantong 226001, PR China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Medical College, Nantong University, Nantong 226001, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Medical College, Nantong University, Nantong 226001, PR China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Zhangjian
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: zyhtgd@hotmail.com.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D005204:Farnesol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D012459:Salicylates / Q000138:chemical synthesis* / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol
keywords: Anti-cancer agents; Cell apoptosis; Diamines; Farnesylthiosalicylic acid; Ras-related signaling pathway