COX Inhibition Profiles and Molecular Docking Studies of the Lignan Hinokinin and Some Synthetic Derivatives

Autor(es)

Borges, Alexandre ^[1] ; Casoti, Rosana ^[2] ; Andrade e Silva, Marcio Luis ^[3] ; da Cunha, Nayane Larissa ^[3] ; da Rocha Pissurno, Ana Paula ^[4] ; Kawano, Daniel Fabio ^[1] ; de Laurentiz, Rosangela da Silva ^[4]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Fac Pharmaceut Sci, Rua Candido Portinari 200, BR-13083871 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Lab Pharmacognosy, Ave Cafe S-N, BR-14040020 Ribeirao Preto, SP - Brazil

^[3] Univ Franca, UNIFRAN, Nucleus Res Exact & Technol Sci, Ave Dr Armando de Sales Oliveira 201, BR-14404600 Franca, SP - Brazil

^[4] Sao Paulo State Univ Julio de Mesquita Filho, UNESP, Fac Engn, Lab Nat Prod & Organ Synth, Ave Brasil 56, BR-15385000 Ilha Solteira, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR INFORMATICS; v. 37, n. 12 DEC 2018.
• Citações Web of Science: 1

Resumo

Figure Encouraged by the anti-inflammatory activity of hinokinin in vivo, which is also observed for the analogues dinitrohinokinin and diidrocubebin, herein we used in vitro and in silico methods to assess their selectivity profiles and predict their binding modes with Cyclooxygenases (COX-1 and 2). The in vitro assays demonstrated dinitrohinokinin is about 13 times more selective for COX-2 than for COX-1, a similar profile observed for the drugs celecoxib (selective index approximate to 9) and meloxicam (selective index approximate to 11). Predictions of the binding modes suggested dinitrohinokinin interacts with COX-2 very similarly to rofecoxib, exploring residues at the hydrophilic pocket of the enzyme that accessible to ligands only in this isoform. This lignan also interacts with COX-1 in a similar mode to meloxicam, blocking the access of the substrate to the catalytic cleft. Therefore, dinitrohinokinin is a promising lead for the design of selective COX-2 inhibitors. (AU)

• Processo FAPESP: 14/07493-5 - Síntese e avaliação biológica de compostos heterocíclicos, análogos de lignanas, obtidos por reação multicomponentes assistida por microondas
• Beneficiário: Rosangela da Silva de Laurentiz
• Modalidade de apoio: Auxílio à Pesquisa - Regular