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

Qiyuan Zhou; Shu Chen; Zoufeng Xu; Gongyuan Liu; Shuyuan Zhang; Zhigang Wang; Man-Kit Tse; Shek-Man Yiu; Guangyu Zhu

doi:10.1002/anie.202302156

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

Qiyuan Zhou (Co-first Author), Shu Chen (Co-first Author), Zoufeng Xu, Gongyuan Liu, Shuyuan Zhang, Zhigang Wang, Man-Kit Tse, Shek-Man Yiu, Guangyu Zhu^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

27 Citations (Scopus)

66 Downloads (CityUHK Scholars)

Abstract

Although multitargeted Pt^IV 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 Pt^IV 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 Pt^IV 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 Pt^IV prodrugs and significantly increases the types of bioactive axial ligands that can be conjugated to a Pt^IV center. © 2023 Wiley-VCH GmbH.

Original language	English
Article number	e202302156
Journal	Angewandte Chemie - International Edition
Volume	62
Issue number	18
Online published	6 Mar 2023
DOIs	https://doi.org/10.1002/anie.202302156
Publication status	Published - 24 Apr 2023

Funding

We thank the Hong Kong Research Grants Council (Grant Nos. CityU 11307419, 11303320, 11302221, and 11313222), the National Natural Science Foundation of China (Grant Nos. 22077108 and 22277103), and the Science Technology and Innovation Committee of Shenzhen Municipality (Grant Nos. JCYJ20210324120004011 and 20200812135215001) for funding support.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

Antitumor Agents
Drug Resistance
Platinum(IV) Prodrug
Pyridine Ligands

Publisher's Copyright Statement

COPYRIGHT TERMS OF DEPOSITED POSTPRINT FILE: This is the peer reviewed version of the following article: Zhou, Q., Chen, S., Xu, Z., Liu, G., Zhang, S., Wang, Z., Tse, M-K., Yiu, S-M., & Zhu, G. (2023). Multitargeted Platinum(IV) Anticancer Complexes Bearing Pyridinyl Ligands as Axial Leaving Groups. Angewandte Chemie - International Edition, 62(18), [e202302156], which has been published in final form at https://doi.org/10.1002/anie.202302156.
This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

RGC Funding Information

RGC-funded

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title = "Multitargeted Platinum(IV) Anticancer Complexes Bearing Pyridinyl Ligands as Axial Leaving Groups",

abstract = "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. {\textcopyright} 2023 Wiley-VCH GmbH.",

keywords = "Antitumor Agents, Drug Resistance, Platinum(IV) Prodrug, Pyridine Ligands",

author = "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",

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doi = "10.1002/anie.202302156",

language = "English",

volume = "62",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley & Sons",

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Multitargeted Platinum(IV) Anticancer Complexes Bearing Pyridinyl Ligands as Axial Leaving Groups. / Zhou, Qiyuan (Co-first Author); Chen, Shu (Co-first Author); Xu, Zoufeng et al.
In: Angewandte Chemie - International Edition, Vol. 62, No. 18, e202302156, 24.04.2023.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Multitargeted Platinum(IV) Anticancer Complexes Bearing Pyridinyl Ligands as Axial Leaving Groups

AU - Zhou, Qiyuan

AU - Chen, Shu

AU - Xu, Zoufeng

AU - Liu, Gongyuan

AU - Zhang, Shuyuan

AU - Wang, Zhigang

AU - Tse, Man-Kit

AU - Yiu, Shek-Man

AU - Zhu, Guangyu

PY - 2023/4/24

Y1 - 2023/4/24

N2 - 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. © 2023 Wiley-VCH GmbH.

AB - 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. © 2023 Wiley-VCH GmbH.

KW - Antitumor Agents

KW - Drug Resistance

KW - Platinum(IV) Prodrug

KW - Pyridine Ligands

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DO - 10.1002/anie.202302156

M3 - RGC 21 - Publication in refereed journal

SN - 1433-7851

VL - 62

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

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ER -

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

Abstract

Funding

UN SDGs

Research Keywords

Publisher's Copyright Statement

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GRF: Synthesis and Anticancer Evaluation of Near-infrared-activatable Platinum Photooxidants

GRF: Development and Biological Evaluation of Ultrasound-activatable Platinum(IV) Anticancer Prodrugs

GRF: Photocaged Platinum Anticancer Prodrugs Targeting the Endoplasmic Reticulum to Conquer Drug Resistance

Cite this

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

Abstract

Funding

UN SDGs

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

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Projects

GRF: Synthesis and Anticancer Evaluation of Near-infrared-activatable Platinum Photooxidants

GRF: Development and Biological Evaluation of Ultrasound-activatable Platinum(IV) Anticancer Prodrugs

GRF: Photocaged Platinum Anticancer Prodrugs Targeting the Endoplasmic Reticulum to Conquer Drug Resistance

Cite this