Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: A computer modelling study
Autore:
Kothekar, V; Sahi, S; Srinivasan, M; Mohan, A; Mishra, J;
Indirizzi:
All India Inst Med Sci, Dept Biophys, New Delhi 110029, India All India Inst Med Sci New Delhi India 110029 s, New Delhi 110029, India
Titolo Testata:
INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS
fascicolo: 1-2, volume: 38, anno: 2001,
pagine: 56 - 63
SICI:
0301-1208(200102/04)38:1-2<56:ROC(AS>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
TIME-DEPENDENT INHIBITION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN G/H SYNTHASE-1; SELECTIVE-INHIBITION; CRYSTAL-STRUCTURE; ARACHIDONIC-ACID; H SYNTHASE-1; H-2 SYNTHASE; AGENTS; ENZYME;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Kothekar, V All India Inst Med Sci, Dept Biophys, Ansari Nagar, New Delhi 110029, India All India Inst Med Sci Ansari Nagar New Delhi India 110029 ia
Citazione:
V. Kothekar et al., "Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: A computer modelling study", I J BIOCH B, 38(1-2), 2001, pp. 56-63

Abstract

The energetics and models of COX-2 complexed with nonsteroidal anti-inflammatory drugs (NSAIDs) having different degrees of selectivity for two isoforms of COX (COX-2 and COX-I) have been studied using computer modelling approach. The models are obtained for complexes of NS398 (NS), a selective COX-2 inhibitor; indoprofen (Ind), a nonselective inhibitor; di-tert-butylbenzofurans (DHDMBFs) with substituents at the 5(th) position: CONH(CH2)(2)OMe (BF1), CONH-c-Pr (BF2), 3-methylene-gamma- butyrolactonyl (BF3) and oxicamsnamely, meloxicam (Mel), piroxicam (Pir) and tenoxicam (Ten). These were optimized using molecular mechanics (MM) and molecular. dynamics (MD) techniques. The binding energies and structures were compared with pharmacological parameters and available results with COX-I. In case of NS a larger difference in the binding energies between COX-2 and COX-I was noticed as compared to that of Ind. It also had stronger interaction with His90 and Tyr355 which is considered important for COX-2 selectivity. There was a difference in the compactness at the channel entrance between COX-2 selective and non-selective ligands. Models with DHDMBFs and oxicams showed a similar correlation. The results were used to design a peptide inhibitor, Tyr-Arg-Cys-Ala-Delta Phe-Cys (Pept) which could fit better in the COX-2 cavity. As per ourMD simulation results this peptide inhibitor showed both higher activity and COX-2 selectivity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 20:08:04