Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 44, Issue 3, Pages 1230-1239Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2008.09.018
Keywords
Benzophenones; Proteases; Guttiferone A; Cathepsin G; SAR; Flexible docking
Categories
Funding
- Brazilian Research Council CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
- APEMIG (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais) [EDT-3310/06]
- FINEP (Financiadora de Estudos e Projetos) [1110/06]
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We have investigated the in vitro inhibition of papain, trypsin, and cathepsins B and G by five benzophenone-type compounds, three natural ones isolated from Garcinia brasiliensis and two synthetic derivatives. The activities of pentaprenylated trihydroxy-substituted benzophenone guttiferone A (1) on all assayed enzymes were approximately 2-69 folds higher than that manifested by mono-hydroxylated tetraprenylated and triprenylated compounds epiclusianone (2) and garciniaphenone (3), respectively, the other natural benzophenones that also inhibited significantly the four enzymes. Differently, the synthetic derivatives 2,2',4-trihydroxybenzophenone (4) and diphenylmethanone (5) have inhibited weakly the studied proteases. Furthermore, compound 1 has bonded preferentially to cathepsin G, once its IC(50) value (2.7 +/- 0.1 mu M) on such peptidase is quite similar to that of the classical inhibitor of serine proteases, chymostatin (2.1 +/- 0.1 mu M). Interesting structure-activity relationships (SARs) were confirmed by flexible docking simulations, likewise the potential usefulness of natural compound 1 as antitumoral drug is strengthened by our results concerning the antiproteolytic activity. (C) 2008 Elsevier Masson SAS. All rights reserved.
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