title: Design, synthesis and cytotoxicity of cell death mechanism of rotundic acid derivatives.
abstract: In the present investigation, 16 new rotundic acid (RA) derivatives modified at the C-3, C-23 and C-28 positions were synthesized. The cytotoxicities of the derivatives were evaluated against HeLa, A375, HepG2, SPC-A1 and NCI-H446 human tumor cell lines by MTT assay. Among these derivatives, compounds 4-7 exhibited stronger cell growth inhibitory than RA and compound 4 was found to be the best inhibition activity on five human tumor cell lines with IC50 <10 μM. The apoptosis mechanism of compound 4 in HeLa cells was investigated by western blot analysis. The results indicated that compound 4 could induce apoptosis through increasing protein expression of cleaved caspase-3 and Bax, and decreasing protein expression of Bcl-2. In summary, the present work suggests that compound 4 might serve as an effective chemotherapeutic candidate.
authors.affiliation: School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: He
authors.forename: Min-Lun
authors.initials: ML
authors.lastname: Nan
authors.forename: Jia-Ming
authors.initials: JM
authors.lastname: Sun
authors.forename: Zhao-Jie
authors.initials: ZJ
authors.lastname: Meng
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C572089:rotundic acid; D053148:Caspase 3