Synthesis and characterization of Schiff base derivatives and its effect on urinary parameters of Wistar rats: A comparative analysis with different classes of diuretics

Abstract

Structural modifications in previously studied substances are one of the strategies commonly used for the discovery of new drugs. In this study, we have reported the synthesis and characterization of a series of Schiff bases (SB) derivatives and the assessment of its effect on urinary parameters of Wistar rats. Different classes of diuretics were included in the study for comparative purposes. The synthesis of the SB 1–6 was carried out by the reaction between ethylenediamine and aldehydes derived from benzaldehyde in ethanol under agitation. Compounds 1–6 were acute orally given to rats (5 mg/kg) to assess its effects on kidney function. SB 1, 3, and 4 increased urinary volume, and showed natriuretic and kaliuretic effects associated with a Ca2+-sparing action; while compound 6 showed only an aquaretic effect. Besides, SB 1, 3, and 4, decreased the number of calcium oxalate crystals in the urine. All the results were similar to those obtained with the thiazide diuretic hydrochlorothiazide (Na+/Cl− cotransporter inhibitor), and do not resemble the characteristics provided by treatment with furosemide (Na+/K+/2Cl− cotransporter inhibitor) or amiloride (epithelial Na+ channel inhibitor). Comparative analysis of 1–6 indicated an inverse correlation between lower pKa values and pharmacological activity. Taking together, this study evaluated a series of SB derivatives for their effect on urine parameters, which the compounds 1, 3 and, 4 showed better activity with pharmacological properties similar to hydrochlorothiazide, even though they do not present similar structures or physical-chemical parameters.