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 anti-hyperglycemic(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.
Method:
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 gauge, 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.
A series of methyl or ethyl 4-(substitutedphenyl/pyridyl)-6-methyl-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (HPM) analogues 4a-g were synthesized and evaluated for larvicidal activity against Anopheles arabiensis. These newly synthesized compounds were characterized by spectral studies such as FT-IR, NMR ( H and C), LC-MS, and elemental analysis. The conformational features and supramolecular assembly of molecules 4a, 4b, and 4e were further analyzed from single crystal X-ray study. The larvicidal activity of these tetrahydropyrimidine pharmacophore series was analyzed based on their relative substituents. Among the synthesized HPM analogous from the series, compounds 4d and 4e both having electron withdrawing chlorine group on phenyl ring at the fourth position of the tetrahydropyrimidine pharmacophore exhibited the most promising larvicidal activity.
A solvent‐assisted grinding method has been used to prepare co‐crystals in substituted dihydropyrimidines (DHPM) that constitutes pharmacologically active compounds. These were characterized using FT‐IR, PXRD, and single‐crystal X‐ray diffraction. In order to explore the possibility of formation of halogen (XB) and hydrogen bonding (HB) synthons in the solid state, co‐crystallization attempts of differently substituted DHPM molecules, containing nitro, hydoxy, and chloro substituents, with different co‐formers, such as 1,4‐diiodo tetrafluorobenzene (1,4 DITFB) and 3‐nitrobenzoic acid (3 NBA) were performed. The XB co‐crystals (C2aXB, C2bXB, and C2cXB) prefer the formation of C−I⋅⋅⋅O/C−I⋅⋅⋅S XB synthon, whereas the HB co‐crystal (C2dHB) is stabilized by N−H⋅⋅⋅O H‐bond formation. Hirshfeld surface analysis revealed that the percentage contribution of intermolecular interactions for XB co‐crystals prefer equal contribution of XB synthon along with HB synthon. Furthermore, the interaction energy was analyzed using energy frameworks, which suggests that their stability, a combination of electrostatics and dispersion, is enhanced through XB/HB in comparison to the parent DHPMs.
The title hydrate crystallizes with two formula units in the asymmetric unit (Z′ = 2). The organic molecules form a dimer, linked by a pair of N—H⋯O hydrogen bonds. Further hydrogen bonding together with weak C—H⋯π and π–π interactions further consolidates the packing, generating a three-dimensional network.
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