Antidiabetic and Antioxidant Effects of Newly Synthesized Pyrimido[1,6-A] Pyrimidine Derivatives in Neonatal Streptozotocin-Induced Diabetic Rats

Abstract

Synthesis of some novel pyrimido[1,6-a]pyrimidine derivatives 4, 8 and 10 was described through the respective reactions of sodium salts of formyl ketones 1, 7 and 9 with 6-aminothiouracil. The characterization of the reaction products was confirmed by using the available elemental analysis and spectral data. One of these derivatives (4b), 1-thioxo-1,2,7,8,9,10-hexahydro-3H-pyrimido[1,6-a]quinazolin-3-one, was tested using sublethal dose level (10 mg/kg b. w./day for 3 weeks) and was found to have potent antihyperglycemic, antihyperlipidemic and antioxidant properties in neonatal streptozotocin-induced (n-STZ) diabetic male and female albino rats.

Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives: Molecular Modeling and Biological Evaluation with Histopathological Effect

“…Regarding liver tissue of groups treated with compound 4 or 5, the histopathology revealed vacuolar degeneration, most prominent being macro-vesicular in rats treated with compound 4 and less so in rats treated with compound 5. Renal tissue of groups treated with compound 4 and compound 5 showed prominent improvement within both glomeruli and tubules, glomeruli showed average cellularity, tubules showed patent lumina, being lined by low cuboidal epithelium, no vacuolar degeneration, no blood casts and no interstitial congestion [24,25].…”

“…Forty male Wister rats were equally divided into five groups: the negative control group receiving 1 mL of distilled water per day for 10 consecutive days and four groups of diabetic rats in which diabetes was induced by fasting for 24 h and subsequent intraperitoneal injection of a single dose of 45 mg/kg body weight of freshly prepared streptozotocin (STZ), dissolved in citrate buffer at pH 4.5, according to [19][20][21][22][23][24][25][26] After 48 h, the blood glucose level was measured for all rats. Rats with glucose levels greater than 300 mg/dL [27].…”

Advances in the chemical and biological diversity of heterocyclic systems incorporating pyrimido[1,6-a]pyrimidine and pyrimido[1,6-c]pyrimidine scaffolds

“…Ring closure of compound 105a was accomplished by an oxidative step by reaction with thionyl chloride to yield xanthine product 103a in 87% yield (Scheme 25). 85 The substituents of 2-(3-noradamantyl)-, such as 2-(adamantan-1-yl)-9-propyl-5,6-dihydro-4H,8H-pyrimidopurine-dione (102), have been veried to be selective antagonists for adenosine A1 receptor. 86,87…”

“…However, additional clinical research is necessary to estimate the safety and effectiveness of the investigated compound in diabetic human beings. 102 …”

Quinazoline pharmacophore in therapeutic medicine

“…Sublethal dosage testing for 1-thioxo-1,2,7,8,9,10-hexahydro-3H-pyrimido[1,6-a]quinazolin-3-one showed that it has remarkable potential in (n-STZ) diabetic male as antihyperglycemic agent (Ahmed et al, 2012). The (n-STZ) diabetic male model used in the study acquired biological and pathological diagnostic sign related to the type 2 diabetes in mankind (Islam and Loot, 2009).…”