Executive Summary : | The present investigation describes the synthesis of four lipid based N-mannich base prodrugs/compounds of norfloxacin and ciprofloxacin via salicylamide as linker and twelve NMannich based benzothiazoles clubbed norfloxacin and ciprofloxacin prodrugs. Moderate to good yield were obtained for the synthesized prodrugs and their physical constants were determined. Spectral analysis was carried out for characterization and structural determination of these synthesized prodrugs (FQF1), 4a-4l and other compounds (FQF2-FQF4). In vitro dissolution studies, enzymatic hydrolysis studies, plasma hydrolysis studies, kinetics studies and stability studies were carried out of selected prodrugs. The dissolution studies revealed that N-Mannich base of norfloxacin with salicylamide and benzothiazoles were found to be more stable at gastric pH than at intestinal pH. The partition coefficient and drug content of synthesized prodrugs were determined. N-Mannich base of amino compounds are helpful in 59 increasing the lipophilicity of parent compounds at physiological pH values by depressing protonation, resulting in enhanced biomembrane passage properties. The synthesized prodrug/compounds were found to possess improved partition coefficient and hence, better permeability across bacterial cell wall as well as selected human lung cancer cell. The synthesized prodrugs were screened for antimicrobial, anthelmintic and cytotoxic activities. Some of the synthesized prodrugs were found to possess significant antimicrobial, anthelmintic and cytotoxic potential due to modified partition coefficient. |