Abstract
Molecular dynamics (MD) simulations were used to investigate the dynamics and host-guest interactions of the inclusion complexes between a potent anti-HIV agent, UC781, and three different types of cyclodextrins (CDs) including βCD, 2,6-dimethyl-βCD (MβCD), and 2-hydroxypropyl-βCD (HPβCD) in aqueous solution with ethanol (EtOH) as a co-solvent. The MD simulation results revealed that EtOH as the co-solvent and the type of cyclodextrin affected the inclusion complex formation. From this study, UC781/MβCD provided the most stable inclusion complex. The competition for the cavity of βCD between UC781 and EtOH and the ensuing occupation of βCD cavities by EtOH resulted in a weaker interaction between βCD and UC781. In HPβCD, a supramolecular complex of UC781−HPβCD−EtOH was formed. The EtOH could easily fill the residual void space of the interior of unoccupied HPβCD due to the movement of UC781. In MβCD, the strong hydrogen bond interactions between the UC781 amide group and the secondary hydroxyl groups of MβCD significantly stabilized the inclusion complex in the presence of EtOH.
Highlights
N-[4-Chloro-3-[(3-methyl-2-buten-1-yl)oxy]phenyl]-2-methyl-3-furancarbothioamide (UC7 81) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with potent inhibition of HIV-1 replication in cell culture systems (50% effective concentration (EC50) only about 3.0 ng/mL) [1,2,3,4]
Molecular dynamics (MD) simulations of the 1:1 inclusion complexes of UC781 in aqueous solution have already been performed by our group [16], as well as on the behaviour of β-cyclodextrin in various water-alcohol mixtures [17]
Influence of EtOH as a Co-Solvent in CD Inclusion Complexation: A MD Study than 3 Å between UC781 and CD molecules were considered as inclusion complex formations in which the phenyl group of UC781 stayed inside the CD cavities
Summary
Kanokthip BOONYARATTANAKALIN 1, Helmut VIERNSTEIN 2, Peter WOLSCHANN 2, Luckhana LAWTRAKUL * 1. Published: Accepted: February 9th 2015 February 9th 2015 doi:10.3797/scipharm.1412-08. © Boonyarattanakalin et al.; licensee Österreichische Apotheker-Verlagsgesellschaft m.
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