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

Osama Mohamed Ahmed,Ahmed M Hussein

doi:10.4172/2161-0444.1000108

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.

Highlights

Pyrimidopyrimidines, analogues of folic acid and an important class of annulated uracil and thiouracil, are pharmacologically useful as powerful inhibitor of aggregation of thrombocytes [1], hepatoprotective [2], bronchodilators, anticancer [35], vasodilators [6,7], antiallergic [8] and antihypertensive [9] agents
Our synthetic strategy commences from the available compound, 6-aminothiouracil and the sodium salts of formyl ketones, which led to the direct construction of the novel fused pyrimido[1,6-a]pyrimidine nucleus
Fusion of 6-aminothiouracil with the formyl salts (1) in piperidine acetate and acetic acid afforded in considerable yields the cyclocondensed pyrimido [1,6-a]pyrimidines 4a-d as outlined in chart (1) [53,54,55]

Summary

Introduction

Pyrimidopyrimidines, analogues of folic acid (one of the B vitamins that is a key factor in the synthesis of nucleic acids RNA and DNA) and an important class of annulated uracil and thiouracil, are pharmacologically useful as powerful inhibitor of aggregation of thrombocytes [1], hepatoprotective [2], bronchodilators, anticancer [35], vasodilators [6,7], antiallergic [8] and antihypertensive [9] agents. As type 2 diabetes mellitus (noninsulin dependent diabetes mellitus, NIDDM) is much more prevalent form of diabetes and is responsible for 90% of the disease prevalence [13,14,15], experimental animal model representing type 2 diabetes, neonatal streptozotocin diabetic rats, is used to assess the antidiabetic as well as the antioxidant efficacy of the tested compound. This animal model develops most of the biochemical and pathological symptoms associated with type 2 diabetes in humans [16]

Methods

Results

Conclusion