Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/21170
Título: Structure-activity relationships for dipeptide prodrugs of acyclovir
Implications for prodrug design
Autor: Santos, Cledir R.
Capela, Rita
Pereira, Claudia S. G. P.
Valente, Emilia
Gouveia, Luis
Pannecouque, Christophe
De Clercq, Erik
Moreira, Rui
Gomes, Paula
Palavras-chave: Chemistry, Medicinal
Data: 2009
Citação: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - Vol. 44, n. 6 (JUN 2009), p. 2339-2346
Resumo: A series of water-soluble dipeptide ester prodrugs of the antiviral acyclovir (ACV) were evaluated for their chemical stability, cytotoxicity, and antiviral activity against several strains of Herpes Simplex-1 and -2, vaccinia, vesicular stomatitis, cytomegalovirus and varicella zoster viruses. ACV dipeptide esters were very active against herpetic viruses, independently of the rate at which they liberate the parent drug. Their minimum cytotoxic concentrations were above 100 mu M and the resulting MCC/EC50 values were lower than those of ACV. When comparing the reactivity of Phe-Gly esters and amides (ACV, zidovudine, paracetamol, captopril and primaquine) in pH 7.4 buffer it was found that the rate of drug release increases with drug's leaving group ability. Release of the parent drug from Phe-Gly in human plasma is markedly faster than in pH 7.4 buffer, thus suggesting that the dipeptide-based prodrug approach can be successfully applied to bioactive agents containing thiol, phenol and amine functional groups. (C) 2008 Elsevier Masson SAS. All rights reserved.. - Funda Ao para a Ciencia e Tecnologia (Portugal) ; CIQUP (PG) ; [SFRHBD/9277/2002]. - Thanks are due to Funda Ao para a Ciencia e Tecnologia (Portugal) for financial support through plurianual funding of research units CIQUP (PG), iMed.UL (RM) and through doctoral grant SFRHBD/9277/2002 (CRS). The authors also thank MEDINFAR for kindly offering acyclovir.
URI: http://hdl.handle.net/10451/21170
DOI: http://dx.doi.org/10.1016/j.ejmech.2008.08.009
ISSN: 0223-5234
Aparece nas colecções:FF - Produção Científica 2000-2009

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