Abstract
Background: The frequent use of antimicrobial agents to treat infections in diabetic patients make them more drug resistant than non-diabetic patients, which accounts for a higher mortality rate of diabetic patients. Therefore, it is a necessity today to synthesize new drugs with dual modes of action as antidiabetic and antibacterial agents. In the present work, new derivatives containing thiazolidinedione and 1,3,4-oxadiaozle have been synthesized and screened for PPAR-γ and antibacterial activities.
Methods: Compounds 5-12 have been synthesized from 2-methoxy benzaldehyde and thiazolidinedione and characterized using different spectroscopic techniques such as IR, NMR, and mass spectrometry. These compounds were tested for in vitro PPAR-γ transactivation, PPAR-γ gene expression, and antibacterial activities. Finally, molecular docking was carried out to see the binding interactions of molecules with the target protein.
Results: All the compounds follow the Lipinski rule suggesting the synthesized derivatives have good drug-likeness properties. Compounds 11 and 12 exhibited promising PPAR-γ transactivation with 73.69% and 76.50%, respectively, as well as showed significant antibacterial activity with comparable MIC of 3.12 μg/disc to standard drug amoxicillin. The docking result was found to be consistent with the in vitro PPAR-γ transactivation results.
Conclusion: Compounds 11 and 12 can be further investigated as lead molecules for the development of new and effective antidiabetic and antibacterial agents.
Keywords: Thiazolidinedione, pharmacokinetics, PPAR-γ, antibacterial, molecular docking, diabetic patients.
Graphical Abstract
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