Niacin-ligated platinum(iv)-ruthenium(ii) chimeric complexes synergistically suppress tumor metastasis and growth with potentially reduced toxicity in vivo

Liwei Shu; Lulu Ren; Yuchen Wang; Tao Fang; Zhijian Ye; Weidong Han; Chao Chen; Hangxiang Wang

doi:10.1039/c9cc09016a

Niacin-ligated platinum(iv)-ruthenium(ii) chimeric complexes synergistically suppress tumor metastasis and growth with potentially reduced toxicity in vivo

Chem Commun (Camb). 2020 Mar 10;56(20):3069-3072. doi: 10.1039/c9cc09016a.

Authors

Liwei Shu¹, Lulu Ren², Yuchen Wang³, Tao Fang⁴, Zhijian Ye⁴, Weidong Han², Chao Chen⁵, Hangxiang Wang⁶

Affiliations

¹ The First Affiliated Hospital, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, 310003, P. R. China. wanghx@zju.edu.cn and Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, P. R. China.
² Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, P. R. China.
³ The First Affiliated Hospital, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, 310003, P. R. China. wanghx@zju.edu.cn and Department of Chemical Engineering, Zhejiang, University, Hangzhou, P. R. China.
⁴ Jinhua People's Hospital, Jinhua, Zhejiang Province 321000, P. R. China.
⁵ College of Life Sciences, Huzhou University, Huzhou, 313000, P. R. China. chenc@zjhu.edu.cn.
⁶ The First Affiliated Hospital, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, 310003, P. R. China. wanghx@zju.edu.cn.

PMID: 32049075
DOI: 10.1039/c9cc09016a

Abstract

Niacin-ligated platinum(iv)-ruthenium(ii) chimeric complexes (PtRu 1-4) have been synthesized and evaluated for their antitumor performance. Using the optimal complex, PtRu-1, we show that this water-soluble chimeric prodrug not only potently inhibits the metastasis and proliferation of tumor cells but also has an unexpectedly higher safety margin in animals compared with the traditionally-used, clinically approved drug cisplatin.

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Body Weight / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cisplatin / chemistry
Cisplatin / pharmacology
Coordination Complexes / chemical synthesis
Coordination Complexes / chemistry
Coordination Complexes / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Inbred ICR
Mice, Nude
Molecular Structure
Neoplasms, Experimental / drug therapy
Neoplasms, Experimental / pathology
Niacin / chemistry
Niacin / pharmacology*
Platinum / chemistry
Platinum / pharmacology*
Ruthenium / chemistry
Ruthenium / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Coordination Complexes
Niacin
Platinum
Ruthenium
Cisplatin