Title:Antidiabetic Activity of Dihydropyrimidine Scaffolds and Structural Insight by Single Crystal X-ray Studies
Volume: 16
Issue: 7
Author(s): Keshab M. Bairagi, Nancy S. Younis, Promise M. Emeka, Ekta Sangtani, Rajesh G. Gonnade, Katharigatta N. Venugopala*, Osama I. Alwassil, Hany E. Khalil and Susanta K. Nayak*
Affiliation:
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982,Saudi Arabia
- Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur 440010, Maharashtra,India
Keywords:
Anti-diabetic, type 2 diabetes mellitus, streptozotocin, dihydropyrimidine, hypoglycemic activity, blood glucose
levels.
Abstract:
Background: This research project is designed to identify the anti-diabetic effects of the
newly synthesized compounds to conclude the perspective of consuming one or more of these new
synthetic compounds for diabetes management.
Introduction: A series of dihydropyrimidine (DHPM) derivative bearing electron releasing and
electron-withdrawing substituent’s on phenyl ring (a-j) were synthesized and screened for antihyperglycemic(
anti-diabetic) activity on streptozotocin (STZ) induced diabetic rat model. The
newly synthesized compounds were characterized by using FT-IR, melting point, 1H and 13C NMR
analysis. The crystal structure and supramolecular features were analyzed through single-crystal
X-ray study. Anti-diabetic activity testing of newly prepared DHPM scaffolds was mainly based
on their relative substituent on the phenyl ring along with urea and thiourea. Among the synthesized
DHPM scaffold, the test compound c having chlorine group on phenyl ring at the ortho position
to the hydropyrimidine ring with urea and methyl acetoacetate derivative shows moderate
lowering of glucose level. However, the title compounds methyl 4-(4-hydroxy-3-methoxyphenyl)-
6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate(g) and ethyl 4-(3-ethoxy-4-
hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate(h) having methoxy
and ethoxy substituents on phenyl ring show significant hypoglycemic activity compared to the
remaining compounds from the Scheme 1.
Methods: The experimental rat models for the study were divided into 13 groups (n = 10); group 1
animals were treated with 0.5% CMC (0.5mL) (vehicle); group 2 were considered the streptozotocin
(STZ)/nicotinamide diabetic control group (DC) and untreated, group 3 diabetic animals were
administered with gliclazide 50 mg/kg and act as a reference drug group. The remaining groups of
the diabetic animals were administered with the newly synthesized dihydropyrimidine compounds
in a single dose of 50 mg/kg orally using the oral gavage, daily for 7 days continuously. The
blood glucose level was measured before and 72 hrs after nicotinamide-STZ injection, for confirmation
of hyperglycemia and type 2 diabetes development.
Results: Blood glucose levels were significantly (p<0.05) reduced after treatment with these derivatives.
The mean percentage reduction for gliclazide was 50%, while that of synthesized compounds
were approximately 36%.
Conclusion: Our result suggests that the synthesized new DHPM derivative containing alkoxy
group on the phenyl ring shows a significant lowering of glucose level compared to other derivatives.