Journal of Veterinary and Applied Sciences

Abstract
Despite the availability of several chemotherapeutic agents for the management of diabetes mellitus, its global prevalence is on the increase, and the disease therefore poses a significant and complex health challenge that calls for intensified research efforts. The present study evaluated the anti-hyperglycemic activity of a series of novel pyrrolidine carboxamide derivatives synthesized by coupling different amines on a proline-glycine based sulphonamide. The reaction products of glycine with either phenylsulphonylproline or tosylproline were coupled in a condensation reaction with different amines to give the target carboxamide derivatives, which were purified using column chromatography, and their structural characteristics elucidated using mass spectrometry (MS), Fourier-transform infrared (FT-IR), carbon-13 nuclear magnetic resonance (¹³C-NMR) and proton nuclear magnetic resonance (¹H-NMR) spectral data. The condensation reaction gave products (Compounds A – D) with outstanding yield. The synthesized compounds were administered to alloxan-induced hyperglycemic rats and their anti-hyperglycemic effect compared with that of a reference drug. The new compounds were also evaluated for their anti-oxidant activity in vitro, using DPPH and FRAP methods. Single dose administration of the new carboxamides compounds caused significant (p < 0.05) reduction in fasting blood glucose of alloxan-induced hyperglycemic rats compared to an untreated hyperglycemic control. Compound B with methyl group para-substituted at the aromatic amine of a tosylpyrrolidine carboxamide gave the best anti-hyperglycemic effect six hours post administration. It was concluded that carboxamide derivatives synthesized by combining glycine proline-based sulphonamides with carboxylic functional group and an amine showed anti-hyperglycemic activity in experimentally induced diabetic rats. These compounds may therefore be considered potential candidates in the development of new class of anti-diabetic drugs.

Keywords: Carboxamides; Anti-diabetic activity; Fasting blood glucose; Hyperglycemia; Alloxan.

How to cite this article:
Onyejekwe BO, Attah SI, Aba PE, Onoja SO, Udem SC and Okoro UC (2024). Anti-hyperglycaemic activity of novel synthesized
carboxamide derivatives in alloxan-induced diabetic rats. Journal of Veterinary and Applied Sciences, 14(1): 618 – 633.

*Correspondence: E-mail: obinna.onyejekwe@unn.edu.ng Phone: +2348035633818

Anti-hyperglycaemic activity of novel synthesized carboxamide derivatives in alloxan-induced diabetic rats

Benedict O. Onyejekwe ^{1 *}, Solomon I. Attah ², Patrick E. Aba ¹, Samuel O. Onoja ³, Samuel C. Udem ¹ and Uchechukwu C. Okoro ²
¹ Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria.
² Department of Pure and Industrial Chemistry, Faculty of Physical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria.
³ Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Michael Okpara University of Agriculture, Umudike, Abia State, Nigeria.