Details

Autor(en) / Beteiligte

• Żołek, Teresa
• Dömötör, Orsolya
• Żabiński, Jerzy

Titel

Binding mechanism of pentamidine derivatives with human serum acute phase protein α1-acid glycoprotein

Ist Teil von

• International journal of biological macromolecules, 2024-05, Vol.266, p.131405-131405, Article 131405

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Drug binding and interactions with plasma proteins play a crucial role in determining the efficacy of drug delivery, thus significantly impacting the overall pharmacological effect. AGP, the second most abundant plasma protein in blood circulation, has the unique capability to bind drugs and transport various compounds. In our present study, for the first time, we investigated whether AGP, a major component of the acute phase lipocalin in human plasma, can bind with pentamidine derivatives known for their high activity against the fungal pathogen Pneumocystis carinii. This investigation was conducted using integrated spectroscopic techniques and computer-based approaches. According to the results, it was concluded that compounds having heteroatoms (-NCH3) in the aliphatic linker and the addition of a Br atom and a methoxy substituent at the C-2 and C-6 positions on the benzene ring, exhibit strong interactions with the AGP binding site. These compounds are identified as potential candidates for recognition by this protein. MD studies indicated that the tested analogues complexed with AGPs reach an equilibrium state after 60 ns, suggesting the stability of the complexes. This observation was further corroborated by experimental results. Therefore, exploring the interaction mechanism of pentamidine derivatives with plasma proteins holds promise for the development of bis-benzamidine-designed pharmaceutically important drugs. •ADMET for tested compounds shows better drug-likeness properties than pentamidine alone•The presence of heteroatoms and a methoxy substituent in pentamidines isessential for strong interactions with AGP•Molecular dynamic simulation of AGP complexes showed the molecular interpretation of the quenching caused by pentamidines