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

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(10), С. 8020 - 8042

Опубликована: Май 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.

Язык: Английский

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

Xingyu Chang

и другие.

Chemical Society Reviews, Год журнала: 2022, Номер 51(13), С. 5518 - 5556

Опубликована: Янв. 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.

Язык: Английский

Процитировано

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

Shu-Rui Li,

Yi-Min Tan,

Ling Zhang

и другие.

Pharmaceutics, Год журнала: 2023, Номер 15(5), С. 1348 - 1348

Опубликована: Апрель 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

Язык: Английский

Процитировано

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

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(3), С. 1982 - 2003

Опубликована: Янв. 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 (

Язык: Английский

Процитировано

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

и другие.

Chemistry - A European Journal, Год журнала: 2024, Номер 30(10)

Опубликована: Янв. 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.

Язык: Английский

Процитировано

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

Yi-Kui Yin,

Heng Zhang

и другие.

Coordination Chemistry Reviews, Год журнала: 2024, Номер 514, С. 215941 - 215941

Опубликована: Май 18, 2024

Язык: Английский

Процитировано

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

Emmanuel Faderin,

Terungwa H. Iorkula,

Omowunmi Rebecca Aworinde

и другие.

Medical Oncology, Год журнала: 2025, Номер 42(2)

Опубликована: Янв. 9, 2025

Язык: Английский

Процитировано

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

и другие.

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(23), С. 10407 - 10416

Опубликована: Июнь 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.

Язык: Английский

Процитировано

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

и другие.

Journal of Medicinal Chemistry, Год журнала: 2022, Номер 65(19), С. 13041 - 13051

Опубликована: Сен. 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.

Язык: Английский

Процитировано

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

и другие.

Journal of Medicinal Chemistry, Год журнала: 2022, Номер 65(13), С. 9447 - 9458

Опубликована: Июль 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.

Язык: Английский

Процитировано

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

Dongge Liu,

Shuqi Yan

и другие.

Toxics, Год журнала: 2022, Номер 10(5), С. 265 - 265

Опубликована: Май 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.

Язык: Английский

Процитировано

40