Driving forces and large scale affinity calculations for piperine/γ-cyclodxetrin complexes: Mechanistic insights from umbrella sampling simulation and DFT calculations.

Autor: Kumar P; Structural Bioinformatics Lab, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, HP 176061, India; Biotechnology division, CSIR-IHBT, Palampur, HP 176061, India; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India., Purohit R; Structural Bioinformatics Lab, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, HP 176061, India; Biotechnology division, CSIR-IHBT, Palampur, HP 176061, India; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India. Electronic address: rituraj@ihbt.res.in.
Jazyk: angličtina
Zdroj: Carbohydrate polymers [Carbohydr Polym] 2024 Oct 15; Vol. 342, pp. 122350. Date of Electronic Publication: 2024 Jun 02.
DOI: 10.1016/j.carbpol.2024.122350
Abstrakt: Piperine (PiP), a bioactive molecule, exhibits numerous health benefits and is frequently employed as a co-delivery agent with various phytomedicines (e.g., curcumin) to enhance their bioavailability. This is attributed to PiP's inhibitory activity against drug-metabolizing proteins, notably CYP3A4. Nevertheless, PiP encounters solubility challenges addressed in this study using cyclodextrins (CDs). Specifically, γ-CD and its derivatives, Hydroxypropyl-γ-CD (HP-γ-CD), and Octakis (6-O-sulfo)-γ-CD (Octakis-S-γ-CD), were employed to form supramolecular complexes with PiP. The conformational space of the complexes was assessed through 1 μs molecular dynamics simulations and umbrella sampling. Additionally, quantum mechanical calculations using wB97X-D dispersion-corrected DFT functional and 6-311 + G(d,p) basis set were conducted on the complexes to examine the thermodynamics and kinetic stability. Results indicated that Octakis-S-γ-CD exhibits superior host capabilities for PiP, with the most favorable complexation energy (-457.05 kJ/mol), followed by HP-γ-CD (-249.16 kJ/mol). Furthermore, two conformations of the Octakis-S-γ-CD/PiP complex were explored to elucidate the optimal binding orientation of PiP within the binding pocket of Octakis-S-γ-CD. Supramolecular chemistry relies significantly on non-covalent interactions. Therefore, our investigation extensively explores the critical atoms involved in these interactions, elucidating the influence of substituted groups on the stability of inclusion complexes. This comprehensive analysis contributes to emphasizing the γ-CD derivatives with improved host capacity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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