Comparative investigation on interaction between potent antimalarials and human serum albumin using multispectroscopic and computational approaches.

This study performed a comparative investigation to explore the interaction mechanisms between two potential antimalarial compounds, JMI 346 and JMI 105, and human serum albumin (HSA), a vital carrier protein responsible for maintaining important biological functions. Our aim was to assess the pharmacological efficiency of these compounds while comprehensively analyzing their impact on the dynamic behavior and overall stability of the protein. A comprehensive array of multispectroscopic techniques, including UV-Vis. spectroscopy, steady-state fluorescence analysis, synchronous fluorescence spectroscopy, three-dimensional fluorescence and circular dichroism spectroscopy, docking studies, and molecular dynamics simulations, were performed to probe the intricate details of the interaction between the compounds and HSA. Our results revealed that both JMI 346 and JMI 105 exhibited promising pharmacological effectiveness within the context of malaria therapy. However, JMI 346 was found to exhibit a significantly higher affinity and only minor altered impact on HSA, suggesting a more favorable interaction with the protein on the dynamic behavior and overall stability of the protein in comparison to JMI 105. Further studies can build on these results to optimize the drug-protein interaction and enable the development of more potent and targeted antimalarial treatments.

Collagen-PVA Films Plasticized with Choline Acetate Ionic Liquid for Sustained Drug Release: UV Shielding, Mechanical, Antioxidant, and Antibacterial Properties.

Collagen and poly(vinyl alcohol) films as topical drug delivery systems were developed by plasticization with glycerol and different concentrations of choline acetate ([Cho]Ac) ionic liquid (IL). The results showed that [Cho]Ac improved the performance of the materials and can serve as an alternative to synthetic plasticizers such as glycerol. Ciprofloxacin (CIP) was used as a model drug to study its release behavior. Ready-to-use films were characterized for their optical opacity, solubility, swelling, mechanical properties, water contact angle, surface morphology, surface roughness, antioxidant, and antimicrobial activities. Moreover, X-ray diffraction and Fourier Transform Infrared (FTIR) studies were carried out for molecular characterization of the films. [Cho]Ac used as a plasticizing agent showed excellent antioxidant properties, mechanical strength, and UV shielding properties. Further, [Cho]Ac improves the roughness and decreases the solubility of films. The in vitro release behavior of CIP was investigated at physiological pH (7.4), and the results showed that CIP was released in a more controlled manner due to the incorporation of [Cho]Ac into the films' matrix, while the films constructed with glycerol exhibited burst release of CIP. Moreover, the films loaded with CIP showed excellent antibacterial activity against Gram-negative (Escherichia coli) as well as Gram-positive (Staphylococcus aureus) bacteria. This study provides insight into the use of choline-based ILs as plasticizing agents for the fabrication of protein-polymer composite films for wound dressing and many other applications.

A multi-spectroscopic and computational simulations study to delineate the interaction between antimalarial drug hydroxychloroquine and human serum albumin.

Hydroxychloroquine (HCQ), a quinoline based medicine is commonly used to treat malaria and autoimmune diseases such as rheumatoid arthritis. Since, human serum albumin (HSA) serves as excipient for vaccines or therapeutic protein drugs, it is important to understand the effect of HCQ on the structural stability of HSA. In this study, the binding mechanism of HCQ and their effect on stability of HSA have been studied using various spectroscopic techniques and molecular dynamic simulation. The UV-VIS results confirmed the strong binding of HCQ with HSA. The calculated thermodynamics parameters confirmed that binding is spontaneous in nature and van der Waals forces and hydrogen bonding are involved in the binding system which is also confirmed by molecular docking results. The steady-state fluorescence confirms the static quenching mechanism in the interaction system, which was further validated by time-resolved fluorescence. The synchronous fluorescence confirmed the more abrupt binding of HCQ with tryptophan residue of HSA compared to Tyr residue of HSA. Isothermal titration calorimetry (ITC) was done to validate the thermodynamics parameters of HSA-HCQ complex in one experiment, supporting the values obtained from the spectroscopic techniques. The circular dichroism (CD) demonstrated that the HCQ affected the secondary structure of HSA protein by reducing their α-helical content. The docking and molecular dynamic simulation results further helped in understanding the effect of HCQ on conformational changes of HSA. Overall, present work defined the physicochemical properties and interaction mechanism of HCQ with HSA that have extensively been elucidated by both in vitro and in silico approaches.Communicated by Ramaswamy H. Sarma.