Site-Selective Interaction of Human Serum Albumin with 4‑Chloro-7-nitro-1,2,3-benzoxadiazole Modified Olanzapine Derivative and Effect of β‑Cyclodextrin on Binding: In the Light of Spectroscopy and Molecular Docking

• Published in: ACS applied bio materials 2019-08, Vol.2 (8), p.3551-3561
• Main Authors: Sasmal, Mihir, Islam, Abu Saleh Musha, Bhowmick, Rahul, Maiti, Debjani, Dutta, Ananya, Ali, Mahammad
• Format: Article
• Language: English
• ISSN: 2576-6422; 2576-6422
• DOI: 10.1021/acsabm.9b00429

Here, we present a detailed investigation on the interaction of 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD) embedded olanzapine derivative (OLA-NBD) with a model transport protein, human serum albumin (HSA). The thermodynamic parameters, ΔH o, ΔS o, and ΔG o, as evaluated by considering the van’t Hoff relationship imply the major contribution of electrostatic/ionic interactions for the HSA–OLA-NBD association. The OLA-NBD induced quenching of HSA emission occurs through static quenching mechanism, indicating a 1:1 association, as portrayed from Benesi–Hildebrand plot, with ∼104 M–1 association constant value, and it is in good harmony with the value estimated from anisotropy experiment. The invariance of the time-resolved decay behavior of HSA with added OLA-NBD concentration, along with matching dependency of the binding constant (K b) value on temperature, also supports the occurrence of static quenching. The effect of β-cyclodextrin on HSA–OLA-NBD binding is characterized by a smaller K b value revealing that the OLA-NBD molecules are gradually removed from β-CD by HSA to achieve its medicinal outcome of drug delivery. The outcome from circular dichroism (CD) illustrates the variation of HSA secondary structure upon interaction with OLA-NBD. Concurrently, HSA–OLA-NBD association kinetics is also explored by applying the fluorescence technique. The possible interaction zone of OLA-NBD in HSA is investigated from AutoDock-based docking simulation study.