The Potential Antidiabetic Activity of Novel Nalidixic Acid-Based 1,2,4-Triazole Derivatives

Diabetes mellitus affects the body's ability to regulate glucose and maintain insulin homeostasis. It has been linked to complications in the heart, kidneys, eyes, and other organs. Recent studies have reported that triazole derivatives can act as antidiabetic drugs. Therefore, this study aimed to evaluate the effects of two newly synthesized triazole derivatives (MMTN and MPTN) of nalidixic acid on streptozotocin (STZ)-induced diabetes in mice.

Nalidixic acid was transformed into 1-ethyl-3-[5-mercapto-4-methyl-(4H)-1,2,4- triazol- 3-yl]-7-methyl-1,8-naphthyridin4(1H)-one (MMTN) and 1-ethyl-3-[5-mercapto- 4-phenyl-(4H)-1,2,4-triazol-3-yl]-7-methyl-1,8-naphthyridin-4(1H)-one (MPTN), through a multistep synthesis process. Forty adult male mice were divided into four groups (n=10): a control group, a diabetic group, a diabetic group treated with MMTN (100 mg/kg i.p), and a diabetic group treated with MPTN (50 mg/kg i.p). Diabetes was induced by intraperitoneal injection of STZ (50 mg/kg) for five consecutive days.

After 18 days, serum and pancreas samples were collected for analysis. Serum glucose levels were increased, pancreatic total antioxidant capacity (TAC) was decreased, and pancreatic malondialdehyde (MDA) levels were increased in the diabetic group.

However, the treatment of diabetic mice with the two compounds caused a notable reduction in blood glucose levels, a rise in serum insulin levels, a decrease in pancreatic MDA, and an increase in TAC levels. Furthermore, pancreatic and duodenal homeobox 1 gene (PDX-1) and insulin 1(INS-1) mRNA expression levels in the pancreas were upregulated in the diabetic + MMTN or MPTN-treated groups.

The synthetic compounds exhibited significant anti-hyperglycemic and antioxidant activity, protected and enhanced the function of pancreatic β-cells, and stimulated insulin secretion.