Molecular modeling of beta-cyclodextrin complexes with nootropic drugs.

Abstract:

:The geometry and structural features of the inclusion complexes of beta-cyclodextrin (beta-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 (MacroModel 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 beta-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 beta-CD complexes of the R and S enantiomers of each guest compound were studied. The almost round beta-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 beta-CD and its inclusion compounds showed acceptable general agreement with information from proton nuclear magnetic resonance studies.

journal_name

J Pharm Sci

authors

Amato ME,Djedaïni F,Pappalardo GC,Perly B,Scarlata G

doi

10.1002/jps.2600811205

subject

Has Abstract

pub_date

1992-12-01 00:00:00

pages

1157-61

issue

12

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)49005-7

journal_volume

81

pub_type

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