Multispectroscopic and Theoretical Investigation on the Binding Interaction of a Neurodegenerative Drug, Lobeline with Human Serum Albumin: Perturbation in Protein Conformation and Hydrophobic-Hydrophilic Surface.

Lobeline (LOB), a naturally occurring alkaloid, has a broad spectrum of pharmacological activities and therapeutic potential, including applications in central nervous system disorders, drug misuse, multidrug resistance, smoking cessation, depression, and epilepsy. LOB represents a promising compound for developing treatments in various medical fields. However, despite extensive pharmacological profiling, the biophysical interaction between the LOB and proteins remains largely unexplored. In the current article, a range of complementary photophysical and cheminformatics methodologies were applied to study the interaction mechanism between LOB and the carrier protein HSA. Steady-state fluorescence and fluorescence lifetime experiments confirmed the static-quenching mechanisms in the HSA-LOB system. "K" (binding constant) of the HSA-LOB system was determined to be 105 M-1, with a single preferable binding site in HSA. The forces governing the HSA-LOB stable complex were analyzed by thermodynamic parameters and electrostatic contribution. The research also investigated how various metal ions affect complex binding. Site-specific binding studies depict Site I as probable binding in HSA by LOB. We conducted synchronous fluorescence, 3D fluorescence, and circular dichroism studies to explore the structural alteration occurring in the microenvironment of amino acids. To understand the robustness of the HSA-LOB complex, we used theoretical approaches, including molecular docking and MD simulations, and analyzed the principal component analysis and free energy landscape. These comprehensive studies of the structural features of biomolecules in ligand binding are of paramount importance for designing targeted drugs and delivery systems.

Protein-binding characteristics of yohimbine, a natural indole alkaloid-based drug for erectile dysfunction.

Even today, talking about sexual dysfunction largely remains a taboo. Therefore less studies have been recorded and fewer remedies given. Erectile dysfunction (ED) is one of the most commonly treated psychological disorders that leads to major distress, interpersonal limitation and reduces the quality of life and marriage. This study aimed to assess a plant-derived molecule, yohimbine (Yoh; a ß-carboline indole alkaloid often used for ED treatment) and its potential binding phenomenon with haemoglobin (Hb). Successful binding of Yoh with Hb is evident from spectroscopic and molecular-docking results. Yoh quenched the fluorescence of Hb efficiently through a static mode. The binding affinity was in the order of 105 M-1 with 1:1 stoichiometry. Thermodynamic analyses concluded that the protein-ligand association was spontaneous and was attributed to entropy-driven exothermic binding. Nonpolyelectrolytic factor was the core, dominating factor. Structural aspects were deciphered through infrared spectroscopy and computational methods. The giant 3D-protein moiety was significantly perturbed through drug binding. Hydrophobic forces and hydrogen bonding participation were stipulated by molecular modelling data. This study reveals the detailed interaction pattern and molecular mechanism of Hb-Yoh binding, correlating the structure-function relationship for the first time, and therefore holds enormous importance from the standpoint of rational and efficient drug design and development.