Design, synthesis, and biological evaluation of disubstituted thiazolidinedione derivatives as pancreatic lipase inhibitors for the management of obesity
Compound <b>16f</b> displayed most potent inhibitory activity with IC<sub>50</sub> value of 4.58 μM. Kinetic studies revealed competitive mode of inhibition for <b>16f</b>, <b>16g</b>, and <b>16r</b> with <i>K<sub>i</sub></i> values 1.479, 1.827, and 1.939 μM; while their <i>V<sub>max</sub></i> values were found to be 0.611, 0.958, and 0.939 μM, respectively. Docking studies confirmed good binding affinities of synthesized derivatives toward the active site of PL. Molecular dynamic simulation of <b>16f</b> revealed stability of the protein-ligand complex. Moreover, compound <b>16f</b> was predicted to have a satisfactory drug likeness profile. Compound <b>16f</b> can be used as a leading candidate for further structural optimization to identify more potent and efficacious PL inhibitors as anti-obesity agents.
Authors
- Rakesh Khator (ORCID: https://orcid.org/0000-0002-3370-355X)
- Atish T. Paul (ORCID: https://orcid.org/0000-0002-8143-5721)
- Vikramdeep Monga (ORCID: https://orcid.org/0000-0003-4004-6241)
- Utkarsh A. Jagtap (ORCID: https://orcid.org/0009-0004-6746-953X)
- Nisha Yadav
- Mhd Shabbu Khan
Institutions
- Central University of Punjab (IN)
- University of Central Punjab (PK)
- Institut Teknologi dan Sains Mandala
Publication Details
- Journal
- Future Medicinal Chemistry
- Published
- 2026-03-26
- DOI
- https://doi.org/10.1080/17568919.2026.2642672
- Primary Topic
- Pharmacology and Obesity Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00