Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 23, Issue 13, Pages 2953-2974Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2015.03.071
Keywords
Thiazolidine-2,4-dione; Aldose reductase; Pim kinase; Protein tyrosine phosphatase 1B; Phosphoinositide 3-kinase; Mitogen activated protein kinase kinase
Funding
- Council of Scientific and Industrial Research (CSIR), New Delhi [02(0111)/12/EMR-II]
- Indian Council of Medical Research (ICMR) [BIC/11(02)/2013, 45/3/2012-BMS/BIF]
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Thiazolidine-2,4-dione is an extensively explored heterocyclic nucleus for designing of novel agents implicated for a wide variety of pathophysiological conditions, that is, diabetes, diabetic complications, cancer, arthritis, inflammation, microbial infection, and melanoma, etc. The current paradigm of drug development has shifted to the structure-based drug design, since high-throughput screenings have continued to generate disappointing results. The gap between hit generation and drug establishment can be narrowed down by investigation of ligand interactions with its receptor protein. Therefore, it would always be highly beneficial to gain knowledge of molecular level interactions between specific protein target and developed ligands; since this information can be maneuvered to design new molecules with improved protein fitting. Thus, considering this aspect, we have corroborated the information about molecular (target) level implementations of thiazolidine-2,4-diones (TZD) derivatives having therapeutic implementations such as, but not limited to, anti-diabetic (glitazones), anti-cancer, anti-arthritic, anti-inflammatory, anti-oxidant and anti-microbial, etc. The structure based SAR of TZD derivatives for various protein targets would serve as a benchmark for the alteration of existing ligands to design new ones with better binding interactions. (C) 2015 Elsevier Ltd. All rights reserved.
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