title: Synthesis and cytotoxic effect of pseudodiosgenyl saponins with thio-ring F.
abstract: Both the sugar moieties and aglycons of steroid saponins play important roles for their bioactivities. In order to test the biological contribution of the glycosyl residue and search new saponins with notable anticancer activity, mono- and di-saccharide pseudodiosgenyl saponins 22-28 together with two pseudodiosgenyl conjugates 29 and 30 were conveniently synthesized, all of which were based on the aglycon 7 bearing the thio-ring F. The cytotoxicity on human cancer cells (MCF-7, HepG-2, A549) for all of the synthesized compounds 7 and 22-30 was evaluated by MTT method. The thio-aglycon 7 when conjugated with sugars exhibited potent cytotoxicity, and the introduction of d-glucosamine into aglycon 7 led to the most potent compound 28. Furthermore, DAPI staining, AV/PI staining, AO-relocation, AO-uptake and LysoTracker Red-uptake assays demonstrated that the cell death caused by neosaponin 28 was at least partially through apoptosis involving lysosomal membrane permeabilization.
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zan
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: National Glycoengineering Research Center, Shandong University, Jinan 250100, PR China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Gu
authors.affiliation: School of Oceanology, Shandong University, Weihai 264209, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China. Electronic address: louhongxiang@sdu.edu.cn.
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Lou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D012503:Saponins / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: C000592789:26-thiodiosgenin 3-O-2'-amino-2'-deoxyglucopyranoside; D000970:Antineoplastic Agents; D012503:Saponins; D013438:Sulfhydryl Compounds
keywords: Apoptosis; Cytotoxicity; Pseudodiosgenyl conjugates; Steroid saponins