A Theoretical Analysis of Interaction Energies and Intermolecular Interactions between Amphotericin B and Potential Bioconjugates Used in the Modification of Nanocarriers for Drug Delivery.

Autor: Cuellar J; Línea de Investigación en Química Computacional, Grupo de Investigación GIFUJ, Departamento de Química, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogota 110231, Colombia., Parada-Díaz L; Línea de Investigación en Química Computacional, Grupo de Investigación GIFUJ, Departamento de Química, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogota 110231, Colombia., Garza J; Departamento de Química, Universidad Autonoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa, Ciudad de Mexico 09340, Mexico., Mejía SM; Línea de Investigación en Química Computacional, Grupo de Investigación GIFUJ, Departamento de Química, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogota 110231, Colombia.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2023 Mar 15; Vol. 28 (6). Date of Electronic Publication: 2023 Mar 15.
DOI: 10.3390/molecules28062674
Abstrakt: Amphotericin B (AmB) is an antibiotic with a wide spectrum of action and low multidrug resistance, although it exhibits self-aggregation, low specificity, and solubility in aqueous media. An alternative for its oral administration is its encapsulation in polymers modified with bioconjugates. The aim of the present computational research is to determine the affinity between AmB and six bioconjugates to define which one could be more suitable. The CAM-B3LYP-D3/6-31+G(d,p) method was used for all computational calculations. The dimerization enthalpy of the most stable and abundant systems at pH = 7 allows obtaining this affinity order: AmB_1,2-distearoyl-sn-glycerol-3-phosphorylethanolamine (DSPE) > AmB_γ-cyclodextrin > AmB_DSPEc > AmB_retinol > AmB_cholesterol > AmB_dodecanol, where DSPEc is a DSPE analog. Quantum theory of atoms in molecules, the non-covalent interactions index, and natural bond orbital analysis revealed the highest abundance of noncovalent interactions for AmB-DSPE (51), about twice the number of interactions of the other dimers. Depending on the interactions' strength and abundance of the AmB-DSPE dimer, these are classified as strong: O-H---O (2), N-H---O (3) and weak: C-H---O (25), H---H (18), C-H---C (3). Although the C-H---O hydrogen bond is weak, the number of interactions involved in all dimers cannot be underestimated. Thus, non-covalent interactions drive the stabilization of copolymers, and from our analysis, the most promising candidates for encapsulating are DSPE and γ-cyclodextrin.
Databáze: MEDLINE
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