Efficient approach to acyloxymethyl esters of nalidixic acid and in vitro evaluation as intra-ocular prodrugs.
Various alkylcarbonyloxymethyl esters of nalidixic acid ranging from 3 to 15 carbon units in the pro-moiety have been prepared and assessed as potential prodrugs. Their chromatographic retention factors k', silicone oil solubilities and in vitro conversion to nalidixic acid by a commercial esterase were determined together with their in vitro antimicrobial activity and cytotoxicity. The preliminary results suggest that silicone oil may have potential for the intra-ocular delivery of antibacterial compounds. Moreover, the in vitro release rate can be controlled by the lipophilicity of the prodrug.
Azéma
Joëlle
J
Groupe de RMN Biomédicale, Laboratoire de Synthèse et Physicochimie de Molécules d'Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex 9, France.
Guidetti
Brigitte
B
Malet-Martino
Myriam
M
Martino
Robert
R
Roques
Christine
C
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D004333:Drug Administration Routes; D004952:Esters / Q000737:chemistry*; D005123:Eye; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D011355:Prodrugs; D012827:Silicone Oils / Q000737:chemistry; D012995:Solubility
D000900:Anti-Bacterial Agents; D004952:Esters; D011355:Prodrugs; D012827:Silicone Oils; D009268:Nalidixic Acid