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Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir
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The derivatization of ACV with amino acids has been used for the development of ACV prodrugs. In fact, the valine derivative of ACV – valacyclovir – is a pro-drug of
widespread use in herpes treatment. Mitra and co-workers have recently reported the synthesis and properties of novel dipeptide prodrugs of ACV, two of which are included in the present work (3c and 3d) [1,2]. The compounds 3a-f prepared were screened for their in vitro antimicrobial activity against Gram positive (Bacillus cereus, Bacillus subtilis) and Gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria, and also for their fungicidal activity using Candida albicans. The antimicrobial activities were evaluated by diameter measurement of haloes formed by growth inhibition caused by compounds 3 at different concentrations in DMSO [3]. Compounds 3 exhibited antimicrobial activity
preferentially against Gram-positive bacteria and were all inactive against Pseudomonas aeruginosa. The minimal inhibitory concentrations (MIC) could be determined for some of the compounds in the concentration range assayed. Further dilutions are being done for MIC determination of most compounds against B. cereus and B. subtilis. The determined MIC were significantly lower than those of typical standards such as ampicilline, cloramphenicol or cyclohexamide. The parent drug, ACV, was also assayed and found to be less active than the corresponding dipeptide ester derivatives. These results suggest that compounds 3 might be activated by bacterial peptidases or actively transported through bacterial cell membrane.
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Pereira, Cláudia S.G.P., Santos, Cledir; Barreira, João C.M.; Moreira, Rui; Ferreira, Isabel C.F.R.; Estevinho, Letícia, Gomes, Paula (2005). Synthesis and antimicrobial activity of dipeptide esters of the anti-rectroviral drug acyclovir. Scientia Pharmaceutica. ISSN 0036-8709. 73:2, Sup, 1. In Abstracts of the Contributions of the Joint Meeting on Medicinal Chemistry