Chemical biology & drug designDec 23, 2025

Testing new pyrimidine-thiazoline compounds for diabetes using enzyme activity and computer modeling

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Updated Mar 20, 2026

Abstract

Compound 8j is a 3-fold more potent inhibitor of α-glucosidase compared to the standard drug acarbose.

Molecular hybridization of pyrimidine-thiazole compounds was explored for their potential as diabetes inhibitors.
Compound 8j showed an IC of 36.23 ± 2.41 μM against α-glucosidase and 38.42 ± 1.63 μM against α-amylase, indicating significant potency.
Compounds 8a and 8j exhibited strong antioxidant activity, with IC values lower than those of ascorbic acid.
Kinetic studies suggested that compounds 4b, 8g, and 8j act as noncompetitive inhibitors.
Molecular docking studies indicated potential protein-ligand interactions for the synthesized compounds.
ADME/T parameter analysis showed these compounds may possess better drug-like properties than acarbose.

Simplified

The prevalence of diabetes mellitus (DM) poses a serious global health concern, given its substantial contribution to mortality rates. Millions of people worldwide are affected by this disease, which is associated with severe complications. Among the different strategies used to regulate diabetes, inhibition of carbohydrate-hydrolyzing enzymes (α-glucosidase and α-amylase) has emerged as a promising therapeutic alternative. Accordingly, the present study explored the concept of molecular hybridization for synthesizing new pyrimidine-thiazole molecular hybrids as potential α-glucosidase and α-amylase inhibitors and antioxidant agents. Among the tested hybrids, compound 8j emerged as the most potent inhibitor with 3-fold (IC = 36.23 ± 2.41 μM) more potency than standard drug acarbose (IC = 103.25 ± 1.45 μM) against α-glucosidase and 2-fold (IC = 38.42 ± 1.63 μM) greater potency than acarbose (IC = 85.00 ± 0.85 μM) against α-amylase. Compounds 8a (IC = 37.84 μM) and 8j (IC = 85.67 μM) displayed the strongest DPPH and NO scavenging activity, respectively, compared to ascorbic acid (IC = 88.40 μM and 102.89 μM, respectively). In addition, kinetic studies revealed that compounds 4b, 8g, and 8j were noncompetitive inhibitors. Molecular docking studies were subsequently carried out to explore the protein-ligand interactions of these compounds. The DFT studies further explored their reactivity characteristics while the ADME/T parameters revealed them to have more drug-likeness properties than acarbose. 50 50 50 50 50 50 50

Key numbers

3×

α-Glucosidase Inhibition Potency Increase

IC of 36.23 ± 2.41 μM for 8j vs. 103.25 ± 1.45 μM for acarbose

2×

α-Amylase Inhibition Potency Increase

IC of 38.42 ± 1.63 μM for 8j vs. 85.00 ± 0.85 μM for acarbose

2×

DPPH Scavenging Activity Increase

IC of 37.84 μM for 8a vs. 88.40 μM for ascorbic acid

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Funding

Competing interests

The authors declare no conflicts of interest.

PubMed

Testing new pyrimidine-thiazoline compounds for diabetes using enzyme activity and computer modeling

Abstract

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Abstract

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Funding

Competing interests

Related papers

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