Synthesis and Preliminary Evaluation of L-Dopa/Benserazide Conjugates as Dual Acting Codrugs

Title: Synthesis and Preliminary Evaluation of L-Dopa/Benserazide Conjugates as Dual Acting Codrugs

Volume: 3 Issue: 10

Author(s): A. Di Stefano, P. Sozio, A. Iannitelli, A. Cocco, G. Orlando and M. Ricciutelli

Affiliation:

Keywords: Parkinson's disease, L-dopa, Benserazide, L-dopa codrugs, Chemical stability, Enzymatic stability

Abstract: The synthesis and “in vitro” chemical and enzymatic stability of Dopa/Benserazide conjugates (2 and 3) as dual acting codrugs are described. These codrugs possess a good lipophilicity (log P = -0.10) when compared to the parent drug LD and benserazide. Furthermore carbonyl and oxalyl spacers provide adequate stability in aqueous buffer solutions (pH 1.3 and 7.4). In 80% rat plasma at 37 °C, catechol esters and amide bonds of the studied derivatives were cleaved, and LD and benserazide were formed in one step. Our findings indicate that synthesized codrugs show good stability toward g.i. hydrolysis releasing LD and benserazide in rat plasma after enzymatic hydrolysis.

Cite this article as:

Di Stefano A., Sozio P., Iannitelli A., Cocco A., Orlando G. and Ricciutelli M., Synthesis and Preliminary Evaluation of L-Dopa/Benserazide Conjugates as Dual Acting Codrugs, Letters in Drug Design & Discovery 2006; 3 (10) . https://dx.doi.org/10.2174/157018006778631947