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Multitargeted Platinum(IV) Anticancer Complexes Bearing Pyridinyl Ligands as Axial Leaving Groups. 2023

Qiyuan Zhou, and Shu Chen, and Zoufeng Xu, and Gongyuan Liu, and Shuyuan Zhang, and Zhigang Wang, and Man-Kit Tse, and Shek-Man Yiu, and Guangyu Zhu
Department of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P. R. China.

Although multitargeted PtIV anticancer prodrugs have shown significant activities in reducing drug resistance, the types of bioactive ligands and drugs that can be conjugated to the Pt center remain limited to O-donors. Herein, we report the synthesis of PtIV complexes bearing axial pyridines via ligand exchange reactions. Unexpectedly, the axial pyridines are quickly released after reduction, indicating their potential to be utilized as axial leaving groups. We further expand our synthetic approach to obtaining two multitargeted PtIV prodrugs containing bioactive pyridinyl ligands: a PARP inhibitor and an EGFR tyrosine kinase inhibitor; these conjugates exhibit great potential for overcoming drug resistance, and the latter conjugate inhibits the growth of Pt-resistant tumor in vivo. This research adds to the array of synthetic methods for accessing PtIV prodrugs and significantly increases the types of bioactive axial ligands that can be conjugated to a PtIV center.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D010984 Platinum A heavy, soft, whitish metal, resembling tin, with atomic number 78, atomic weight 195.084, symbol Pt. It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". Platinum Black
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

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