DESIGN, SYNTHESIS AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF NEW METFORMIN DERIVATIVES


Monther F. Mahdi, Inam S. Arif, Najwan K. Jubair

Abstract


Objective: The purpose of this work was to enhance oral bioavailability of metformin by incorporation of different amino acid residues through the glycolic acid spacer.

Methods: 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.

Results: In vivo 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.

Conclusion: From this study, it was concluded that incorporation of these amino acids or their methyl esters maintained or enhanced the antihyperglycemic effect of metformin. 


Keywords


Metformin, Intestinal di/tripeptide transporter, Amino acids, In vivo antidiabetic study

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About this article

Title

DESIGN, SYNTHESIS AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF NEW METFORMIN DERIVATIVES

Keywords

Metformin, Intestinal di/tripeptide transporter, Amino acids, In vivo antidiabetic study

DOI

10.22159/ijpps.2017v9i1.15250

Date

31-12-2016

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 1, 2017 Page: 239-245

Online ISSN

0975-1491

Authors & Affiliations

Monther F. Mahdi
Department of pharmacology and pharmaceutical chemistry, college of pharmacy, Al- Mustansiriyia University, Baghdad, Iraq
Iraq

Inam S. Arif
Department of pharmacology and pharmaceutical chemistry, college of pharmacy, Al- Mustansiriyia University, Baghdad, Iraq

Najwan K. Jubair
Department of pharmacology and pharmaceutical chemistry, college of pharmacy, Al- Mustansiriyia University, Baghdad, Iraq


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