title: Design, synthesis, and anticancer evaluation of long-chain alkoxylated mono-carbonyl analogues of curcumin.
abstract: Curcumin is a nontoxic phenolic compound that modulates the activity of several cellular targets that have been linked with cancers and other chronic diseases. However, the efficacy of curcumin in the clinic has been limited by its poor bioavailability and rapid metabolism in vivo. We have previously reported the design and discovery of series of 5-carbon linker-containing mono-carbonyl analogues of curcumin (MACs) as anti-cancer agents. In continuation of our ongoing research, we designed and synthesized 37 novel long-chain alkoxylated MACs for anti-cancer evaluation here. The MTS assay was used to determine the cytotoxicity of compounds in gastrointestinal cancer cells. Compounds 5, 28, and 29 showed strongest inhibition against gastric cancer cell proliferation and were subjected to further analysis. The effects of 5, 28, and 29 on cell apoptosis were measured by flow cytometry. Expression levels of Bcl-2, cleaved poly ADP-ribose polymerase (PARP), and pro-caspase-3 were detected by western blotting. Compounds 5, 28, and 29 induced apoptosis in human gastric carcinoma cells, increased PARP cleavage, and decreased expression of Bcl-2 and pro-caspase-3 protein. We then showed that compound 28, which possessed the strongest activity among the test compounds in vitro, exhibited significant tumor inhibition in SGC7901-driven xenograft mouse model. Taken together, the novel compound 28 could be further explored as an effective anticancer agent for the treatment of human gastric cancer.
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China.
authors: Qiaoyou
authors: Q
authors: Weng
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors: Lili
authors: L
authors: Fu
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors: Gaozhi
authors: G
authors: Chen
authors: Department of Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China.
authors: Junguo
authors: J
authors: Hui
authors: Department of Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China.
authors: Jingjing
authors: J
authors: Song
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors: Jianpeng
authors: J
authors: Feng
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors: Dengjian
authors: D
authors: Shi
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors: Yuepiao
authors: Y
authors: Cai
authors: Department of Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China. Electronic address: jjstcty@sina.com.
authors: Jiansong
authors: J
authors: Ji
authors: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: wzmcliangguang@163.com.
authors: Guang
authors: G
authors: Liang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin
keywords: Anticancer drug; Apoptosis; Drug design; Gastric cancer; MACs