Red‐Light Photocatalytic Activation Of Pt(IV) Anticancer Prodrugs Using Methylene Blue DOI
Ana C. Carrasco, Greta Bajetto, Stefano Scoditti

et al.

ChemCatChem, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Abstract Catalysis‐based approaches offer versatile strategies for activating anticancer prodrugs, potentially allowing precise control over drug release and localization within tumor tissues while reducing systemic toxicity. In this study, we explore the role of phenothiazine dye methylene blue ( MB + ) as a photocatalyst in conjunction with biologically relevant electron donors to facilitate red‐light conversion two Pt(IV) complexes, denoted cis,cis,trans ‐[PtCl 2 (NH 3 (O CCH CH COOH) ] 1 trans ‐[Pt(O 1R,2R‐ (DACH)(ox)] ), into cisplatin oxaliplatin, respectively. Combining spectroscopic techniques (NMR, UV–vis, flash photolysis) computational methods, reveal that doubly reduced (leucomethylene blue, LMB triggers reductive elimination axial ligands precursors, generating corresponding Pt(II) drugs. vitro experiments conducted on human cervical cancer cell line CaSki, which harbors multiple copies integrated HPV‐16 genome, nontumoral cells (HaCat) demonstrate coadministration prodrugs improves ’s antiproliferative efficacy cells, particularly under red light exposure. This enhancement could be attributed catalytic production species cellular environment.

Language: Английский

Reduction of anticancer prodrugs cis-diamminetetrachloroplatinum(IV) and ormaplatin by a large series of thiols: Phenomenal structure-reactivity correlations DOI

Yanqing Xia,

Hongwu Tian,

Zili Yin

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: 1329, P. 141394 - 141394

Published: Jan. 11, 2025

Language: Английский

Citations

1
Pt(iv) anticancer prodrugs bearing an oxaliplatin scaffold: what do we know about their bioactivity? DOI
Alvaro Lopez-Sanchez, Hélène Bertrand

Inorganic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(6), P. 1639 - 1667

Published: Jan. 1, 2024

Oxaliplatin( iv ) prodrugs, classified by the role of their axial ligands, are presented with a focus on in vitro stability and activity vivo models, illustrating potential to address current Pt-based chemotherapy's main limitations.

Language: Английский

Citations

7
Current Status of Novel Multifunctional Targeted Pt(IV) Compounds and Their Reductive Release Properties DOI Creative Commons

Lingwen Xu,

Xiangyu Kong, Xinzhi Li

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(4), P. 746 - 746

Published: Feb. 6, 2024

Platinum-based drugs are widely used in chemotherapy for various types of cancer and considered crucial. Tetravalent platinum (Pt(IV)) compounds have gained significant attention been extensively researched among these drugs. Traditionally, Pt(IV) reduced to divalent (Pt(II)) after entering cells, causing DNA lesions exhibiting their anti-tumor effect. However, the available evidence indicates that some derivatives may differ from traditional mechanism exert effect through overall structure. This review primarily focuses on existing literature regarding targeted Pt(II) compounds, with a specific emphasis vivo mode action properties reduction release multifunctional compounds. provides comprehensive summary design synthesis strategies employed selectively target enzymes (glucose receptor, folate, telomerase, etc.) or substances (mitochondria, oleic acid, etc.). Furthermore, it thoroughly examines summarizes rational design, action, reductive capacity novel such as those targeting p53-MDM2, COX-2, lipid metabolism, dual drugs, drug delivery systems. Finally, this aims provide theoretical support development new

Language: Английский

Citations

7
Pt(IV) Complexes as Anticancer Drugs and Their Relationship with Oxidative Stress DOI Creative Commons

Vlad Iova,

R.C. Tincu,

Ioana Scrobotă

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 981 - 981

Published: April 17, 2025

Despite continuous research, cancer is still a leading cause of death worldwide; therefore, new methods management improvement are emerging. It well known that in the pathophysiology cancer, oxidative stress (OS) significant factor. Nevertheless, there currently no quick or easy way to identify OS patients using blood tests. Currently, treatments, Pt(IV) complexes preferred Pt(II) terms adverse effects, drug resistance, and administration methods. Intracellular reductants convert their analogs, which Pt compounds with anti-carcinogenic effects. Our aim was find out if could be used assess indicators and, consequently, monitor development cancer. In this review, we analyzed previous research PubMed Google Scholar public databases verify potential use management. We found two main serum antioxidants, glutathione ascorbic acid, easily measured conventional methods, react favorably complexes. results suggest as therapeutic anticancer drugs diagnosis agents. However, further must conducted hypothesis.

Language: Английский

Citations

0
Recent advances in antitumor Pt(IV) complexes: Dual targeting and chemoimmunotherapy DOI
Daniil Spector,

A. Zharova,

Vladislav Bykusov

et al.

Coordination Chemistry Reviews, Journal Year: 2025, Volume and Issue: 541, P. 216808 - 216808

Published: May 21, 2025

Language: Английский

Citations

0
Platinum(IV) Prodrugs Incorporating an Indole-Based Derivative, 5-Benzyloxyindole-3-Acetic Acid in the Axial Position Exhibit Prominent Anticancer Activity DOI Open Access
Angelico D. Aputen, Maria George Elias, Jayne Gilbert

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2181 - 2181

Published: Feb. 11, 2024

Kinetically inert platinum(IV) complexes are a chemical strategy to overcome the impediments of standard platinum(II) antineoplastic drugs like cisplatin, oxaliplatin and carboplatin. In this study, we reported syntheses structural characterisation three that incorporate 5-benzyloxyindole-3-acetic acid, bioactive ligand integrates an indole pharmacophore. The purity structures resultant complexes, P-5B3A, 5-5B3A 56-5B3A were confirmed via spectroscopic means. evaluated for anticancer activity against multiple human cell lines. All proved be considerably more active than carboplatin in most lines tested. Remarkably, demonstrated greatest activity, displaying GI50 values between 1.2 150 nM. Enhanced production reactive oxygen species paired with decline mitochondrial as well inhibition histone deacetylase also by HT29 colon cells.

Language: Английский

Citations

2
Drugs from drugs: New chemical insights into a mature concept DOI Creative Commons
Eloy Lozano Baró, Federica Catti,

Carolina Estarellas

et al.

Drug Discovery Today, Journal Year: 2024, Volume and Issue: unknown, P. 104212 - 104212

Published: Oct. 1, 2024

Language: Английский

Citations

2
Red-Light Photocatalytic Activation Of Pt(IV) Anticancer Prodrugs Using Methylene Blue DOI Creative Commons
Ana C. Carrasco, Greta Bajetto, Stefano Scoditti

et al.

Published: March 6, 2024

Catalysis-based approaches offer versatile strategies for activating anticancer prodrugs, potentially allowing precise control over drug release and localization within tumor tissues, while reducing systemic toxicity. In this study, we explore the role of phenothiazine dye methylene blue (MB+) as a photocatalyst in conjunction with biologically relevant electron donors to facilitate red-light conversion two Pt(IV) complexes, denoted cis,cis,trans-[PtCl2(NH3)2(O2CCH2CH2COOH)2] (1) trans-[Pt(O2CCH2CH2COOH)21R,2R-(DACH)(ox)] (2), into cisplatin oxaliplatin, respectively. Combining spectroscopic techniques (NMR, UV-Vis, flash photolysis) computational methods, reveal that doubly reduced MB+ (leucomethylene blue, LMB) triggers reductive elimination axial ligands precursors, generating corresponding Pt(II) drugs. vitro experiments conducted on human cervical cancer cell line CaSki, which harbors multiple copies integrated HPV-16 genome, non-tumoral cells (HaCat) demonstrate co-administration prodrugs improves MB+'s antiproliferative efficacy cells, particularly under red light exposure. This enhancement arises from catalytic production species cellular environment.

Language: Английский

Citations

1
Machine Learning-Based Prediction of Reduction Potentials for PtIV Complexes DOI
Vincenzo Vigna, Tânia Cova, Sandra C. C. Nunes

et al.

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: 64(9), P. 3733 - 3743

Published: April 29, 2024

Some of the well-known drawbacks clinically approved PtII complexes can be overcome using six-coordinate PtIV as inert prodrugs, which release corresponding four-coordinate active species upon reduction by cellular reducing agents. Therefore, key factor prodrug mechanism action is their tendency to reduced which, when involved outer-sphere type, measured value potential. Machine learning (ML) models used effectively capture intricate relationships within complex data, leading highly accurate predictions potentials and other properties, offering significant insights into electrochemical behavior potential applications. In this study, a machine learning-based approach for predicting based on relevant molecular descriptors presented. Leveraging data set experimentally determined diverse range descriptors, proposed model demonstrates remarkable predictive accuracy (MSE = 0.016 V2, RMSE 0.13 V, R2 0.92). Ab initio calculations different algorithms feature engineering techniques have been employed systematically explore relationship between structure similarity Specifically, it has investigated whether these compounds described combining ML across combinations constitutional, topological, electronic descriptors. Our results not only provide crucial factors influencing but also offer rapid effective tool rational design with tailored properties pharmaceutical This significantly expedite development screening novel candidates. The analysis principal components features extracted from highlights significance structural 2D Atom Pairs type lowest unoccupied orbital energy. just 20 appropriately selected notable separation achieved.

Language: Английский

Citations

1
Red-Light Photocatalytic Activation Of Pt(IV) Anticancer Prodrugs Using Methylene Blue DOI Creative Commons
Ana C. Carrasco, Greta Bajetto, Stefano Scoditti

et al.

Published: Aug. 16, 2024

Catalysis-based approaches offer versatile strategies for activating anticancer prodrugs, potentially allowing precise control over drug release and localization within tumor tissues, while reducing systemic toxicity. In this study, we explore the role of phenothiazine dye methylene blue (MB+) as a photocatalyst in conjunction with biologically relevant electron donors to facilitate red-light conversion two Pt(IV) complexes, denoted cis,cis,trans-[PtCl2(NH3)2(O2CCH2CH2COOH)2] (1) trans-[Pt(O2CCH2CH2COOH)21R,2R-(DACH)(ox)] (2), into cisplatin oxaliplatin, respectively. Combining spectroscopic techniques (NMR, UV-Vis, flash photolysis) computational methods, reveal that doubly reduced MB+ (leucomethylene blue, LMB) triggers reductive elimination axial ligands precursors, generating corresponding Pt(II) drugs. vitro experiments conducted on human cervical cancer cell line CaSki, which harbors multiple copies integrated HPV-16 genome, non-tumoral cells (HaCat) demonstrate co-administration prodrugs improves MB+'s antiproliferative efficacy cells, particularly under red light exposure. This enhancement could be attributed catalytic production species cellular environment.

Language: Английский

Citations

1