Design, Synthesis, Biological Evaluation of Tnf-α Inhibi- Tors As Antidiabetic Agents
Chavan Rajashree , Chandhere Komal , Bhosale Ashok
1 HOD and Asso. Professor, 2 P.G. Scholar , 3 Professor and HOD , 1,2 Dept. of Pharmaceutical Chemistry, 3 Dept. of Pharmaceutics PDEA'S Seth Govind Raghunath Sable College of Pharmacy, Saswad, Pune - 412301, Maharashtra, India.
Corresponding Author: Chavan Rajashree
E-mail: rajchavan18@gmail.com
Submission: 20.12.2018 Acceptance: 07.01.2019 Publication: 15.02.2019
https://www.doi.org/10.63778/PDEASIJRAAS-ARJCPL/2019_21511
Abstract: The weight loss in obese patients is associated with reduced Tumor necrosis factor-α (TNF-α) production and ameliorated insulin resistance. TNF-α has been shown to be an important mediator of insulin resistance linked to obesity. TNF-α interferes with insulin-signaling by inhibiting tyrosine kinase activity of the insulin receptor and the serine phosphorylation of insulin receptor substrate-1 (IRS-1). Thiazolidinediones serve as a boom in the antidiabetic therapy by increasing the sensitivity of insulin receptors towards insulin. The present study aims at designing novel thiazolidinediones with TNF-α inhibitory action thereby increasing the insulin sensitivity. The goal of our research work is to synthesize newer thiazolidinedione derivatives via convenient and efficient synthetic pathways which will offer an advantage of having both TNF-α inhibitory and antidiabetic activities particularly in obese people. The hybrid molecules with two basic pharmacophores viz Chalcone and Thiazolidinediones having potential to show both TNF-α inhibitory activity as well as antidiabetic activity are synthesized. A series of 5-(4-(4-(3-(4-substituedphenyl) prop-2-en-1-one) phenoxy)benzylidene)thiazolidine-2,4-dione are synthesized 1 by designing the appropriate schemes and characterized further by TLC, FTIR and H NMR. The synthesized compounds were further evaluated for antidiabetic activity and TNF-α inhibitory activity. The results show that the compounds inhibit TNF-α along with comparable antidiabetic activity. The study can be extended further to establish the correlation of TNF-α inhibition with increased insulin sensitivity.