To obtain next-generation metal drugs that can overcome the deficiencies of platinum (Pt) drugs and treat cancer more effectively, we proposed to develop a multitargeted palladium (Pd) agent to the tumor microenvironment (TME) based on the specific residue(s) of human serum albumin (HSA). To this end, we optimized a series of Pd(II) 2-benzoylpyridine thiosemicarbazone compounds to obtain a Pd agent (5b) with significant cytotoxicity. The HSA-5b complex structure revealed that 5b bound to the hydrophobic cavity in the HSA IIA subdomain and then His-242 replaced a leaving group (Cl) of 5b, coordinating with the Pd center. The results showed that the 5b/HSA-5b complex had significant capacity of inhibiting tumor growth, and HSA optimized the therapeutic behavior of 5b. In addition, we confirmed that the 5b/HSA-5b complex inhibited tumor growth through multiple actions on different components of TME: killing cancer cells, inhibiting tumor angiogenesis, and activating T cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.3c00248 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Deciphering Saquinavir-Bovine Serum Albumin Interactions: Spectroscopic and Computational Insights.
J Mol Recognit
January 2025
Biopolymer Modeling and Protein Chemistry Laboratory, Centre for Advanced Studies in Crystallography and Biophysics, University of Madras, Chennai, India.
Bovine serum albumin (BSA) plays a crucial role as a carrier protein in plasma, binding various ligands, including drugs. Understanding the interaction between BSA and saquinavir, an antiretroviral drug, is essential for predicting its pharmacokinetics and pharmacodynamics. We employed spectroscopic approaches, including circular dichroism spectrometry and fluorescence spectroscopy, to investigate the binding of saquinavir to BSA.
View Article and Find Full Text PDFProbing the Biomolecular Interactions of DNA/HSA with the New Sn(IV) Complex and Computational Perspectives: Design, Synthesis, Characterization, Anticancer Activity, and Molecular Modeling Approach.
J Med Chem
December 2024
Department of Pharmacy, Faculty of Medical Sciences, National University (Ibb Branch), Ibb 46654, Yemen.
Article Synopsis
- A Sn(IV) complex was synthesized using the ligands 2,2'-bipyridyl and indole-3-carboxylic acid, and thoroughly characterized with various analytical techniques such as elemental analysis, UV-vis, and NMR.
- Binding studies revealed that the Sn(IV) complex interacts strongly with the phosphate backbone of DNA and with the subdomain IIA of human serum albumin (HSA), indicating significant electrostatic interactions.
- The nature of the ligands attached to the Sn(IV) center influenced its binding properties, suggesting the complex has potential as an effective anticancer drug candidate.
Nonlinear van't Hoff Behavior in the Interaction of Two Water-Soluble Porphyrins with Bovine Serum Albumin (BSA).
ACS Omega
December 2024
Instituto de Física, Universidade Federal de Goiás, Goiânia, Goiás 74690-900, Brazil.
Thermodynamic analysis of the binding process of water-soluble negatively charged -tetrakis(-sulfonatophenyl) (TPPS) and positively charged -tetrakis(4-methylpyridyl) (TMPyP) porphyrins with bovine serum albumin (BSA) at different temperatures was carried out based on the data of BSA quenching fluorescence by porphyrins. The comparison of binding constants ( ) shows that negatively charged TPPS possesses higher affinity to BSA than positively charged TMPyP. Thermodynamic characteristics of the binding process were obtained in accordance with the van't Hoff theory by processing nonlinear dependences of ln on inverse absolute temperature within the framework of two models: taking into account the dependence or independence of the change in the standard heat capacity (Δ ) on temperature.
View Article and Find Full Text PDFThe presence of NSAIDs may affect the binding capacity of serum albumin to the natural products hymecromone and umbelliferone.
Int J Biol Macromol
December 2024
Departament of Organic Chemistry, Institute of Chemistry, Federal Rural University of Rio de Janeiro (UFRRJ), Seropédica 23890-000, RJ, Brazil. Electronic address:
The natural products 7-hydroxycoumarin (7HC) and 7-hydroxy-4-methylcoumarin (7H4MC), known as umbelliferone and hymecromone, respectively, are one of the simplest structural examples from coumarin's family, showing several biological activities. Bovine serum albumin (BSA) is the main model protein used in laboratory experiments to characterize the biophysical capacity of potential drugs to be carried until the target in the bloodstream. Thus, the interaction BSA:7HC and BSA:7H4MC was biophysically characterized by circular dichroism (CD), steady-state, and time-resolved fluorescence techniques combined with molecular docking calculations via cross-docking approach to better correlate with the biological medium.
View Article and Find Full Text PDFLapachol, a natural food component, interacts with human serum albumin: Insights of its impact on the pharmacokinetics of clinically used drugs.
Int J Biol Macromol
December 2024
Department of Chemistry, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS), University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal. Electronic address:
Lapachol (LAP), a natural 1,4-naphthoquinone used in popular medicine in South America, is an antioxidant and antimicrobial compound in teas and infusions and used as a food additive; however, its interactive profile with the main protein carrier of compounds in the human bloodstream (human serum albumin, HSA) was not still characterized. Additionally, the impact of LAP in binding clinically drugs to albumin is still unknown. Thus, the present work describes the interaction HSA:LAP using different biophysical techniques, i.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!