Natural polyprenylated benzophenones inhibiting cysteine and serine proteases

Natural polyprenylated benzophenones inhibiting cysteine and serine proteases

Author Martins, Felipe T. Google Scholar
Assis, Diego M. Google Scholar
Santos, Marcelo H. dos Google Scholar
Camps, I. Google Scholar
Veloso, Marcia P. Google Scholar
Juliano, Maria A. Autor UNIFESP Google Scholar
Alves, Lira C. Google Scholar
Doriguetto, Antonio C. Google Scholar
Institution Univ Fed Alfenas
Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords Benzophenones
Guttiferone A
Cathepsin G
Flexible docking
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
FINEP (Financiadora de Estudos e Projetos)
Grant number FAPEMIG: EDT-3310/06
FINEP (Financiadora de Estudos e Projetos): 1110/06
Date 2009-03-01
Published in European Journal of Medicinal Chemistry. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 44, n. 3, p. 1230-1239, 2009.
ISSN 0223-5234 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1230-1239
Access rights Closed access
Type Article
Web of Science ID WOS:000264558600035

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