title: Design, synthesis and biological evaluation of C6-modified celastrol derivatives as potential antitumor agents.
abstract: New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468). The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84-0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer.
authors.affiliation: Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China. tangkaiyong@huatuodrug.com.
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Tang
authors.affiliation: Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China. qqhuang@sat.ecnu.edu.cn.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Shanghai Hotmed Sciences Co., Ltd., Shanghai 201201, China. zengjiafeng@huatuodrug.com.
authors.forename: Jafeng
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Shanghai Hotmed Sciences Co., Ltd., Shanghai 201201, China. wuguangming@huatuodrug.com.
authors.forename: Guangming
authors.initials: G
authors.lastname: Wu
authors.affiliation: Shanghai Hotmed Sciences Co., Ltd., Shanghai 201201, China. huangjinwen@hotmail.com.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Huang
authors.affiliation: Shanghai Hotmed Sciences Co., Ltd., Shanghai 201201, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Pan
authors.affiliation: Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China. wlu@chem.ecnu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol