DESIGN, SYNTHESIS AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF NEW METFORMIN DERIVATIVES

Abstract

<p><strong>Objective: </strong>The purpose of this work was to enhance oral bioavailability of metformin by incorporation of different amino acid residues through the glycolic acid spacer.</p><p><strong>Methods: </strong>Two series of metformin derivatives (V a-e) and (VI a-e) were synthesized by incorporation of five amino acids (glycine, alanine, phenylalanine, proline and GABA amino butyric acid) and their methyl esters respectively into metformin through glycolic acid spacer and preliminary evaluation for the antihyperglycemic activity was carried out using streptozotocin-induced diabetic rats model.</p><p><strong>Results: </strong><em>In vivo</em> anti-hyperglycemic activity of the final compounds (V a-e) and (VI a-e) showed that compounds (V b, V c, VI c and V e) produced higher percent of decrease in blood glucose level compared to metformin after 5 h of the treatment while compounds (VI b, VI c, V d, VI d, V e and VI e) showed profound effect after 24 h of the treatment. Although compounds (V a, VI a, V b and V c) showed a significant decrease in blood glucose level at 5 h but their effect diminished at 24 h. Compound (V e) showed higher anti-hyperglycemic effect than metformin and its effect continued up to 24 h.</p><p><strong>Conclusion: </strong>From this study, it was concluded that incorporation of these amino acids or their methyl esters maintained or enhanced the antihyperglycemic effect of metformin. </p>