title: Hybrid molecule from Farnesylthiosalicylic acid-diamine and phenylpropenoic acid as Ras-related signaling inhibitor with potent antitumor activities.
abstract: Novel series of Farnesylthiosalicylic acid-diamine/phenylpropenoic acid hybrids were designed and synthesized. Their in vitro growth inhibitory assays showed that most compounds displayed strong antiproliferation activity against seven cancer cells. Especially, the new hybrid 12 f, by the conjugation of 10a with ferulic acid, could selectively suppress the proliferation of tumor cells and display significantly lower toxicities to normal cells than its intermediate 10a. Furthermore, 12 f dose-dependently induced SMMC-7721 cell apoptosis. Additionally, our observations demonstrated that 12 f inhibited both Ras-related signaling and phosphorylated NF-κB synergistically, which may be advantageous to the strong antitumor activities of 12 f. Our findings suggest that these novel hybrids may hold a great promise as therapeutic agents for the intervention of human cancers.
authors.affiliation: School of Pharmacy, Nantong University, Nantong, 226001, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ling
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Xuemin
authors.initials: X
authors.lastname: Wang
authors.forename: Xianghua
authors.initials: X
authors.lastname: Li
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Dai
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003959:Diamines / Q000737:chemistry / Q000494:pharmacology; D005204:Farnesol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D010666:Phenylpropionates / Q000737:chemistry* / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012459:Salicylates / Q000737:chemistry* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003959:Diamines; D016328:NF-kappa B; D010666:Phenylpropionates; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol; D018631:ras Proteins
keywords: NF-κB; Ras-related signaling pathway; antitumor agents; farnesylthiosalicylic acid; hybrids; phenylpropenoic acid