Abstract
DIURETIC EFFECT OF NOVEL STRUCTURAL ANALOGUES OF ETHACRYNIC ACID

Syed Ayaz Ali*, Afreen Begum, Santosh N. Mokale and Shweta More

ABSTRACT

Ethacrynic acid is a highly effective clinically used loop diuretic. Literature reveals that it can produce diuresis in patients with chronic renal failure. The present research study aims to develop novel structural analogues of ethacrynic acid having greater diuretic effect. Designed compounds were docked against NKCC2 (PDB: 5DBX) using Ethacrynic acid as standard. After evaluation of docking results compounds were slected for synthesis. Synthesis was completed in three steps with the Convenient synthetic route as shown in the scheme. The Structures of novel synthesized molecules were confirmed by spectral characterization such as FTIR, 1HNMR, 13CNMR and Mass spectrometry. Toxicological and ADME studies were done to ensure safety and drug like properties of the novel compounds.Ten structural analogues of ethacrynic acid were synthesized and evaluated for diuretic effect in albino wistar rats. The diuretic effect was measured by calculating different parameters such as urine volume, urinary electrolyte levels (Na, K, Cl ions mmol/lit), urine pH, and conductivity. Diuretic index was calculated to correlate the diuretic potential of novel synthesized compounds. Compounds C1, C3, C4, C5, C6 have maximum docking score as well as found with higher diuretic index/ diuretic action.We have succeeded in developing structural analogues of ethacrynic acid. All the Compounds were found with diuretic activity. Compound C3, C5, C6, were found with higher diuretic effect where as compound C4 was found with the excellent diuretic activity. The research studies presented here was found to be helpful in development of new therapeutic agents with high diuretic potential.

Keywords: Structural analogues, Ethacrynic acid, Diuretic potential, Molecular docking, Spectroscopy, Diuretic Index.


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