Publication Type : Journal Article
Publisher : Chemical Biology & Drug Design
Source : Chemical Biology & Drug Design, Volume 98, Number 1, p.49-59 (2021)
Url : https://onlinelibrary.wiley.com/doi/abs/10.1111/cbdd.13846
Keywords : Enzyme Inhibitors, Fluorescence spectroscopy, Molecular modelling, Pancreatic lipase
Campus : Kochi
School : School of Pharmacy
Department : Pharmaceutical Chemistry & Analysis
Year : 2021
Abstract : Abstract Pancreatic Lipase (PL) is a key enzyme responsible for the digestion of 50%–70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole-TZD hybrid analogues were synthesized, characterized and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole-3-carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Analogues 6d and 6e exerted potent PL inhibitory activity (IC50-6.19 and 8.96 µM, respectively). Further, these analogues exerted a competitive mode of PL inhibition. Moreover, molecular modelling studies were in agreement with the in vitro results (Pearson's r = .8682, p < .05). The fluorescence spectroscopic analysis further supported the strong binding affinity of these analogues with PL. A molecular dynamics study (20 ns) indicated that these analogues were stable in a dynamic environment. Thus, the present study highlighted the potential role of indole-thiazolidinedione hybrid analogues as potential PL inhibitors and further optimization might result in the development of new PL inhibitory lead candidates.
Cite this Research Publication : Ginson George, Auti Prashant S., and Paul Atish T., “Design, synthesis and biological evaluation of N-substituted indole-thiazolidinedione analogues as potential pancreatic lipase inhibitors”, Chemical Biology & Drug Design, vol. 98, pp. 49-59, 2021.