Glycyrrhetinic Acid as a Hepatocyte Targeting Ligand-Functionalized Platinum(IV) Complexes for Hepatocellular Carcinoma Therapy and Overcoming Multidrug Resistance DOI

Xiaochao Huang,

Guimei Li,

Huifang Li

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(10), P. 8020 - 8042

Published: May 10, 2024

Promising targeted therapy options to overcome drug resistance and side effects caused by platinum(II) drugs for treatment in hepatocellular carcinoma are urgently needed. Herein, six novel multifunctional platinum(IV) complexes through linking agents glycyrrhetinic acid (GA) were designed synthesized. Among them, complex 20 showed superior antitumor activity against tested cancer cells including cisplatin than simultaneously displayed good liver-targeting ability. Moreover, can significantly cause DNA damage mitochondrial dysfunction, promote reactive oxygen species generation, activate endoplasmic reticulum stress, eventually induce apoptosis. Additionally, effectively inhibit cell migration invasion trigger autophagy ferroptosis HepG-2 cells. More importantly, demonstrated stronger tumor inhibition ability or the combo of cisplatin/GA with almost no systemic toxicity A549 xenograft models. Collectively, could be developed as a potential anti-HCC agent treatment.

Language: Английский

Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases DOI
Yunlong Lu, Xiaoyan Ma,

Xingyu Chang

et al.

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(13), P. 5518 - 5556

Published: Jan. 1, 2022

In this review, the recent progress in gold( i ) and iii complexes are comprehensively summarized, their anti-cancer activity mechanism of action documented.

Language: Английский

Citations

150
Comprehensive Insights into Medicinal Research on Imidazole-Based Supramolecular Complexes DOI Creative Commons

Shu-Rui Li,

Yi-Min Tan,

Ling Zhang

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(5), P. 1348 - 1348

Published: April 27, 2023

The electron-rich five-membered aromatic aza-heterocyclic imidazole, which contains two nitrogen atoms, is an important functional fragment widely present in a large number of biomolecules and medicinal drugs; its unique structure beneficial to easily bind with various inorganic or organic ions molecules through noncovalent interactions form variety supramolecular complexes broad potential, being paid increasing amount attention regarding more contributions imidazole-based for possible application. This work gives systematical comprehensive insights into research on complexes, including anticancer, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, anti-inflammatory aspects as well ion receptors, imaging agents, pathologic probes. new trend the foreseeable near future toward chemistry also prospected. It hoped that this provides help rational design drug agents effective diagnostic pathological

Language: Английский

Citations

43
Simultaneous Activation of Immunogenic Cell Death and cGAS-STING Pathway by Liver- and Mitochondria-Targeted Gold(I) Complexes for Chemoimmunotherapy of Hepatocellular Carcinoma DOI
Fuwei Li,

Zhenfan Wen,

Chuanxing Wu

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(3), P. 1982 - 2003

Published: Jan. 23, 2024

Induction of immunogenic cell death (ICD) and activation the cyclic GMP-AMP synthase stimulator interferon gene (cGAS-STING) pathway are two potent anticancer immunotherapeutic strategies in hepatocellular carcinoma (HCC). Herein, 12 liver- mitochondria-targeting gold(I) complexes (

Language: Английский

Citations

22
Development of Platinum Complexes for Tumor Chemoimmunotherapy DOI
S. Jin, Yan Guo, Xiaoyong Wang

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(10)

Published: Jan. 3, 2024

Abstract Platinum complexes are potential antitumor drugs in chemotherapy. Their impact on tumor treatment could be greatly strengthened by combining with immunotherapy. Increasing evidences indicate that the activity of platinum is not limited to chemical killing effects, but also extends immunomodulatory actions. This review introduced general concept chemoimmunotherapy and summarized progress as chemoimmunotherapeutic agents recent years. developed into inducers immunogenic cell death, blockers immune checkpoint, regulators signaling pathway, modulators microenvironment, etc. The synergy between chemotherapeutic effects reinforces complexes, helps them circumvent drug resistance systemic toxicity. exploration for may create new opportunities revive discovery metal anticancer drugs.

Language: Английский

Citations

16
Metal N-heterocyclic carbene complexes as potential metallodrugs in antitumor therapy DOI
Yifan Zhang,

Yi-Kui Yin,

Heng Zhang

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 514, P. 215941 - 215941

Published: May 18, 2024

Language: Английский

Citations

16
Platinum nanoparticles in cancer therapy: chemotherapeutic enhancement and ROS generation DOI

Emmanuel Faderin,

Terungwa H. Iorkula,

Omowunmi Rebecca Aworinde

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(2)

Published: Jan. 9, 2025

Language: Английский

Citations

2
Target Profiling of an Iridium(III)-Based Immunogenic Cell Death Inducer Unveils the Engagement of Unfolded Protein Response Regulator BiP DOI
Xiaolin Xiong, Ke-Bin Huang, Yuan Wang

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(23), P. 10407 - 10416

Published: June 3, 2022

Clinical chemotherapeutic drugs have occasionally been observed to induce antitumor immune responses beyond the direct cytotoxicity. Such effects are coined as immunogenic cell death (ICD), representing a "second hit" from host system tumor cells. Although chemo-immunotherapy is highly promising, ICD inducers remain sparse with vague drug–target mechanisms. Here, we report an endoplasmic reticulum stress-inducing cyclometalated Ir(III)–bisNHC complex (1a) new inducer, and based on this compound, clickable photoaffinity probe was designed for target identification, which unveiled engagement of master regulator protein BiP (binding immunoglobulin protein)/GRP78 unfolded response pathway. This has confirmed by series cellular biochemical studies including fluorescence microscopy, thermal shift assay, enzymatic assays, so forth, showing capability 1a destabilization. Notably, besides 1a, previously reported KP1339, mitoxantrone, oxaliplatin were also found engage interaction, suggesting important role in eliciting anticancer immunity. We believe that ICD-related information work will help understand mode action beneficial designing agents high specificity improved efficacy.

Language: Английский

Citations

55
A Photoactivated Sorafenib-Ruthenium(II) Prodrug for Resistant Hepatocellular Carcinoma Therapy through Ferroptosis and Purine Metabolism Disruption DOI

Yidan Lai,

Nong Lu,

Shuangling Luo

et al.

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(19), P. 13041 - 13051

Published: Sept. 22, 2022

The curative effect of sorafenib in hepatocellular carcinoma (HCC) is limited and resistance remains a major obstacle for HCC. To overcome this obstacle, new photoactive sorafenib-Ru(II) complex Ru-Sora has been designed. Upon irradiation (λ = 465 nm), rapidly releases generates reactive oxygen species, which can oxidize intracellular substances such as GSH. Cellular experiments show that irradiated highly cytotoxic toward Hep-G2 cells, including sorafenib-resistant Hep-G2-SR cells. Compared to sorafenib, significant photoactivated chemotherapeutic against cancer cells 3D multicellular tumor spheroids. Furthermore, inducing apoptosis ferroptosis proved by GSH depletion, GPX4 downregulation, lipid peroxide accumulation. Metabolomics results suggest exerts photocytotoxicity disrupting the purine metabolism, expected inhibit development. This study provides promising strategy enhancing chemotherapy combating drug-resistant HCC disease.

Language: Английский

Citations

50
Developing a Copper(II) Agent Based on His-146 and His-242 Residues of Human Serum Albumin Nanoparticles: Integration To Overcome Cisplatin Resistance and Inhibit the Metastasis of Nonsmall Cell Lung Cancer DOI
Ming Jiang, Zhenlei Zhang, Wenjuan Li

et al.

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(13), P. 9447 - 9458

Published: July 4, 2022

To overcome the resistance of nonsmall cell lung cancer (NSCLC) cells to cisplatin and inhibit their metastasis, we proposed develop a Cu(II) agent based on specific residue(s) HSA nanoparticles (NPs) for multitargeting tumor microenvironment (TME). this end, not only synthesized four 2-hydroxy-3-methoxybenzaldehyde thiosemicarbazone compounds (C1–C4), obtaining Cu compound (C4) with significant cytotoxicity by studying structure–activity relationships, but also revealed binding mechanism C4 through X-ray crystallography confirmed successful construction new HSA-C4 NPs delivery system. inhibited A549cisR growth optimized anticancer behavior C4. We further C4/HSA-C4 NP TME resistance: killing acting mtDNA inducing apoptosis, polarizing M2-type macrophages M1-type, inhibiting angiogenesis.

Language: Английский

Citations

44
Adverse Effects of Perfluorooctane Sulfonate on the Liver and Relevant Mechanisms DOI Creative Commons
Pingwei Wang,

Dongge Liu,

Shuqi Yan

et al.

Toxics, Journal Year: 2022, Volume and Issue: 10(5), P. 265 - 265

Published: May 19, 2022

Perfluorooctane sulfonate (PFOS) is a persistent, widely present organic pollutant. PFOS can enter the human body through drinking water, ingestion of food, contact with utensils containing PFOS, and occupational exposure to have adverse effects on health. Increasing research shows that liver major target damage tissue disrupt its function; however, exact mechanisms remain unclear. In this study, we reviewed cells, as well function, provide reference for subsequent studies related toxicity injury caused by PFOS.

Language: Английский

Citations

40