Synthesis and biological evaluation of thiazolidine-2,4-dione-pyrazole conjugates as antidiabetic, anti-inflammatory and antioxidant agents

Garima Bansal; Shamsher Singh; Vikramdeep Monga; Punniyakoti Veeraveedu Thanikachalam; Pooja Chawla

doi:10.1016/j.bioorg.2019.103271

Synthesis and biological evaluation of thiazolidine-2,4-dione-pyrazole conjugates as antidiabetic, anti-inflammatory and antioxidant agents

Bioorg Chem. 2019 Nov:92:103271. doi: 10.1016/j.bioorg.2019.103271. Epub 2019 Sep 10.

Authors

Garima Bansal¹, Shamsher Singh², Vikramdeep Monga¹, Punniyakoti Veeraveedu Thanikachalam³, Pooja Chawla⁴

Affiliations

¹ Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga 142001, Punjab, India.
² Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India.
³ Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga 142001, Punjab, India. Electronic address: nspkoti2001@gmail.com.
⁴ Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga 142001, Punjab, India. Electronic address: pvchawla@gmail.com.

PMID: 31536952
DOI: 10.1016/j.bioorg.2019.103271

Abstract

A series of fourteen novel thiazolidine-2,4-dione derivatives clubbed with pyrazole moiety were synthesized via four step reaction procedure. Reactions were monitored by thin layer chromatography and were characterized by physicochemical and spectrophotometric (IR, Mass, ¹HNMR and ¹³CNMR) analysis. The spectral data were in good agreement with their structures. The title compounds were docked against peroxisome proliferated activated receptors (PPAR-γ) and alpha-amylase and further evaluated for in vivo and in vitro antidiabetic, in vitro anti-inflammatory and antioxidant activities. Compound GB14 exhibited significant blood glucose lowering activity and was also found to be active inhibitor of alpha-amylase. Compound GB7 was found to be potent anti-inflammatory agent in terms of reducing inflammatory markers (TNF-α, IL-β, MDA) and also showed antioxidant activity to good extent. Therefore, these compounds may be considered as promising candidates for the development of new antidiabetic agents.

Keywords: Alpha amylase; Anti-inflammatory; Antidiabetic; Antioxidant; PPAR-γ; Thiazolidine-2,4-dione.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Antioxidants / chemical synthesis
Antioxidants / chemistry
Antioxidants / pharmacology*
Blood Glucose / drug effects
Dose-Response Relationship, Drug
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / pharmacology*
Interleukin-1beta / antagonists & inhibitors
Interleukin-1beta / metabolism
Malondialdehyde / antagonists & inhibitors
Malondialdehyde / metabolism
Mice
Mice, Inbred C57BL
Molecular Docking Simulation
Molecular Structure
PPAR gamma / antagonists & inhibitors
PPAR gamma / metabolism
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Structure-Activity Relationship
Thiazolidinediones / chemistry
Thiazolidinediones / pharmacology*
Tumor Necrosis Factor-alpha / antagonists & inhibitors
Tumor Necrosis Factor-alpha / metabolism
alpha-Amylases / antagonists & inhibitors
alpha-Amylases / metabolism

Substances

Anti-Inflammatory Agents, Non-Steroidal
Antioxidants
Blood Glucose
Hypoglycemic Agents
Interleukin-1beta
PPAR gamma
Pyrazoles
Thiazolidinediones
Tumor Necrosis Factor-alpha
thiazolidine-2,4-dione
pyrazole
Malondialdehyde
alpha-Amylases