Zohor Mohammad Mahdi Alzhrani, Mohammad Mahboob Alam and Syed Nazreen* Pages 998 - 1008 ( 11 )
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.
Thiazolidinedione, pharmacokinetics, PPAR-γ, antibacterial, molecular docking, diabetic patients.
Department of Chemistry, Faculty of Science, Albaha University, Albaha, Department of Chemistry, Faculty of Science, Albaha University, Albaha, Department of Chemistry, Faculty of Science, Albaha University, Albaha