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Titolo:
Molecular dynamics simulation of the interaction of 5-keto substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran derivatives with cyclooxygenase-2
Autore:
Kothekar, V; Sahi, S; 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:
CURRENT SCIENCE
fascicolo: 6, volume: 80, anno: 2001,
pagine: 764 - 770
SICI:
0011-3891(20010325)80:6<764:MDSOTI>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
TIME-DEPENDENT INHIBITION; PROSTAGLANDIN-H SYNTHASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SELECTIVE-INHIBITION; ENDOPEROXIDE SYNTHASE; CRYSTAL-STRUCTURE; H-2 SYNTHASE; ACTIVE-SITE; AGENTS; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Physical, Chemical & Earth Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Kothekar, V All India Inst Med Sci, Dept Biophys, New Delhi 110029, India All India Inst Med Sci New Delhi India 110029 110029, India
Citazione:
V. Kothekar et al., "Molecular dynamics simulation of the interaction of 5-keto substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran derivatives with cyclooxygenase-2", CURRENT SCI, 80(6), 2001, pp. 764-770

Abstract

We present here results on molecular dynamics simulation of three 7-tert-butylbenzofurans with substituents at the fifth position: CONH(CH2)(2)OMe (BF1), CONH-c-Pr(cyclopropyl) (BF2) and 3-methylene-gamma -butyrolactonyl (BF3), complexed with cyclooxygenase-2 (COX-2), a target for non-steroidal anti-inflammatory drugs (NSAIDs), Perturbative changes in the enzyme structure, energetics of interaction and points of contact are monitored, Our results showed that difference in root mean square deviations (RMSDs) of backboneCa atoms in interdomain contact and heme binding loops, better interactionwith adjoining helical segments, H-bonding and electrostatic interaction with Arg120, Tyr355, Arg513, His90 and more 'relaxed conformation' at the channel entrance led to better COX-2 selectivity by BF1, Hydrophobic contactswith Met113, Pro86 and Va189 increase COX-2 selectivity. Higher potency ofBF3 is due to its better interaction with membrane-anchoring region of COX-2 and larger mobility of residues in the cavity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 23:31:37