Theoretical Study of Isoindolines to Identify them as Cyclooxygenase-1 and -2 Inhibitors by Docking Simulations

This work describes a theoretical study of two series ofisoindolines 1(a-h) and 2(a-h) as possible COX-1 and COX-2inhibitors by Docking method. Whereas, the same study was carriedout for isoindolilamides 3-5, which have shown anti-inflammatoryand analgesic effects, as well as ibuprofen 6 and dihydro...

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Detalles Bibliográficos
Autores: José Correa-Basurto, Karla S. Alavés Carbajal, Evelyn T. J. Sánchez Escalante, José Trujillo Ferrara, Teresa Mancilla
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2007
País:México
Institución:Instituto Politécnico Nacional
Repositorio:Redalyc-IPN
OAI Identifier:oai:redalyc.org:47551209
Acceso en línea:https://www.redalyc.org/articulo.oa?id=47551209
Access Level:acceso abierto
Palabra clave:Multidisciplinaria (Ciencias Naturales y Exactas)
anti
Docking
analgesic
amino acids
Isoindolines
Descripción
Sumario:This work describes a theoretical study of two series ofisoindolines 1(a-h) and 2(a-h) as possible COX-1 and COX-2inhibitors by Docking method. Whereas, the same study was carriedout for isoindolilamides 3-5, which have shown anti-inflammatoryand analgesic effects, as well as ibuprofen 6 and dihydrodimethylbenzofuran7, which are well-known as excellent anti-inflammatory.Compounds 6 and 7 were used to identify the active sites on thesetwo enzymes and compared with those obtained from isoindolinesunder docking studies. The analysis of Docking results show thatcompounds 1(a-h) and 2(a-h) could inhibit both cyclooxygenases(COXs), due to the fact that they act in the same region as those takenas reference (3-7) make several interactions with the amino acidresidues that conform the active sites of both COXs. ΔG values wereobtained for all compounds, they are between –9.87 and –6.65(Kcal/mol, COX-1) and -10.96 and –6.28 (Kcal/mol, COX-2), beingCOX-1-1h and COX-2-1h complexes more stable. Therefore, Kd(��M) values were obtained, they are in the range of 0.06 and 13.5 inCOX-1 and finally the values between 0.01 and 24.7 in COX-2,where 1h shows more affinity to both COX-1 and COX-2.