title: Synthesis of methyl 2-cyano-3,12-dioxo-18β-olean-1,9(11)-dien-30-oate analogues to determine the active groups for inhibiting cell growth and inducing apoptosis in leukemia cells.
abstract: Fourteen of the methyl 2-cyano-3,12-dioxo-18β-olean-1,9(11)-dien-30-oate (CDODO-Me-12, 10d) analogues with different structures of ring C were synthesized to determine the active groups for inhibiting cell growth and inducing apoptosis in human leukemia HL-60 cells. An unsaturated group in ring C was required to maintain the ability to inhibit cell growth and induce apoptosis. Compound 10e with 9(11),12-dien in ring C displayed comparable apoptosis induction ability to 10d associated with decreased levels of c-FLIP, but not Mcl-1 and XIAP. Compound 10e had decreased ability to deplete GSH compared to compound 10d. Compound 10e represents a new active compound acting through a different mechanism from that of compound 10d.
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang-110016, China. linxiang.zhao@vip.sina.com.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Li
authors.forename: Yuetong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Jing
authors.forename: Linxiang
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D006131:Growth Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D006131:Growth Inhibitors; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D005978:Glutathione; D006034:Glycyrrhetinic Acid