Computationally guided design and synthesis of pyrimidine–oxazole hybrids as novel antidiabetic agents: kinetic and molecular interaction studies

Jul 30, 2025Computational biology and chemistry

Computer-designed pyrimidine-oxazole compounds as new diabetes treatments: reaction speed and molecule interaction studies

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Abstract

The most potent compound, analog 8, demonstrates an IC of 5.20 ± 0.10 μM against α-amylase.

Diabetes mellitus is characterized by high blood glucose levels due to insufficient insulin production or cellular unresponsiveness to insulin.
Symptoms of diabetes include blurry vision, excessive urination, and slow healing sores, with potential severe complications if untreated.
Novel pyrimidine-based oxazole derivatives were synthesized and assessed for anti-diabetic activity.
These derivatives exhibited moderate to excellent inhibitory effects against α-amylase and α-glucosidase, with analog 8 showing the strongest activity.
Molecular docking and simulations were conducted to evaluate the enzyme inhibition potential and structural stability of the compounds.
ADMET analysis indicated that these compounds have no toxicological effects.

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Diabetes mellitus (DM) is one of the complex and chronic endocrine diseases often characterized by high blood glucose level. Diabetes is due to either pancreases not producing insulin which convert excess of blood glucose to glycogen, or the cell of body becoming unresponsive to insulin's effect. Primary symptom of DM includes blurry vision, excess urination and slow healing sores but if not diagnosed earlier and treated, it is associated with some severe secondary impairment like cardiovascular diseases, diabetic neuropathy, diabetic nephropathy and Alzheimer's diseases etc. The focus of current research work is to design and synthesized a novel pyrimidine based oxazole derivatives (1-10) having promising anti-diabetic activity. These derivatives were synthesized by using reagent grade starting material i.e. 4-chloro-6-methylpyrimidin-2-amine. Structural conformation of the synthesized derivative was acquired byH-NMR andC-NMR and their molecular weight were confirmed by HREI-MS. These compound exhibit moderate to excellent biological potential against α-amylase and α-glucosidase in comparison to standard acarbose IC= 10.50 ± 0.20 μM and IC= 10.80 ± 0.10 μM. Among these derivatives, analog 8 having IC= 5.20 ± 0.10 μM against α-amylase and IC= 5.70 ± 0.10 μM against α-glucosidase emerged as a most potent compound of the series with excellent inhibitory potency of target enzyme. The biological interaction of the newly synthesized derivatives was studied through molecular docking to assess their enzyme inhibition potency. Furthermore, the molecular dynamic (MD) simulation, density functional theory (DFT) studies are also performed in order to assess their structural conformational changes, stability and reactivity under dynamic environment. Absorption distribution metabolism excretion and toxicity (ADMET) analysis showed that these potent compounds have no toxicological effect. 1 13 50 50 50 50

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Computationally guided design and synthesis of pyrimidine–oxazole hybrids as novel antidiabetic agents: kinetic and molecular interaction studies

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