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Molecular Modeling of β‐Cyclodextrin Complexes with Nootropic Drugs

1992; Elsevier BV; Volume: 81; Issue: 12 Linguagem: Inglês

10.1002/jps.2600811205

1520-6017

Maria E. Amato, Florence Djedaïni, Giuseppe Pappalardo, Bruno Perly, Giuseppe Scarlata,

Drug Solubulity and Delivery Systems

The geometry and structural features of the inclusion complexes of β‐cyclodextrin (β‐CD) with the chiral antiamnesic drugs (±)‐1‐benzyl‐4‐hydroxymethylpyrrolidin‐2‐one (WEB‐1868). (±)‐1‐benzenesulfonyl‐5‐ethoxypyrrolidin‐2‐one (RU‐35929), and (±)‐1‐(3‐pyridinlysulfonyl)‐5‐ethoxypyrrolidin‐2‐one (RU‐47010) were studied by the molecular modeling method (Macro Model interactive computer program). Docking procedures yielded the most stable complexes, which showed the aromatic ring of the guests inside the cavity and the pyrrolidinone ring out from the side of the β‐CD secondary hydroxyl groups. The binding energies were essentially due to hydrogen‐bonded structures involving the C=O group of the guests. Selective interactions allowed chiral discrimination, and accordingly, separate β‐CD complexes of the R and S enantiomers of each guest compound were studied. The almost round β‐CD structure, in all the cases, assumed an elliptic shape on passing from the isolated molecule to the docked complex. The optimized structures and conformations of β‐CD and its inclusion compounds showed acceptable general agreement with information from proton nuclear magnetic resonance studies.