|
|||||
|
|
Hybrid Molecule from Farnesylthiosalicylic Acid-diamine and Phenylpropenoic Acid as Ras-related Signaling Inhibitor with Potent Antitumor Activities |
|
| Authors: | Yong Ling Zhiqiang Wang Xuemin Wang Xianghua Li Xinyang Wang Wei Zhang Hong Dai Li Chen Yihua Zhang |
| Affiliation: | 1. School of Pharmacy, Nantong University, Nantong, 226001 China State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009 China;2. School of Pharmacy, Nantong University, Nantong, 226001 China Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009 China;3. School of Pharmacy, Nantong University, Nantong, 226001 China;4. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009 China |
| 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 12f , 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, 12f dose-dependently induced SMMC-7721 cell apoptosis. Additionally, our observations demonstrated that 12f inhibited both Ras-related signaling and phosphorylated NF-κB synergistically, which may be advantageous to the strong antitumor activities of 12f . Our findings suggest that these novel hybrids may hold a great promise as therapeutic agents for the intervention of human cancers. |
| Keywords: | antitumor agents farnesylthiosalicylic acid hybrids NF-κB phenylpropenoic acid Ras-related signaling pathway |