title: Combretastatin A-4 Analogue: A Dual-Targeting and Tubulin Inhibitor Containing Antitumor Pt(IV) Moiety with a Unique Mode of Action.
abstract: Three new Pt(IV) complexes comprising a combretastatin A-4 analogue were designed and synthesized. The resulting antitumor Pt(IV) complexes could significantly improve the antiproliferative activity and overcome the drug resistance of cisplatin in vitro. Interestingly, these novel compounds not only can carry the DNA binding Pt(II) warhead into the cancer cells but also have a small molecule fragment that can inhibit tubulin polymerization. Among them, complex 13, which was attached to an inhibitor of tubulin at one axial position of Pt(IV) octahedral coordination sphere, could effectively enter cancer cells, arrest the cell cycle in HepG-2 cancer cells at G2/M phases, and induce activation of caspases triggering apoptotic signaling via the mitochondrial-dependent apoptosis pathways. Moreover, complex 13 has the ability to effectively inhibit the tumor growth in the HepG-2 xenograft model without causing significant loss of animal body weight in comparison with cisplatin.
authors: Xiaochao
authors: X
authors: Huang
authors: Rizhen
authors: R
authors: Huang
authors: Shaohua
authors: S
authors: Gou
authors: Zhimei
authors: Z
authors: Wang
authors: Zhixin
authors: Z
authors: Liao
authors: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University , Guilin 541004, China.
authors: Hengshan
authors: H
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001632:Bibenzyls / Q000737:chemistry*; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011355:Prodrugs / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D017382:Reactive Oxygen Species / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001632:Bibenzyls; D009944:Organoplatinum Compounds; D011355:Prodrugs; D017382:Reactive Oxygen Species; D014404:Tubulin; D050257:Tubulin Modulators; C040105:combretastatin; D004247:DNA