Chadha Navriti, Bahia Malkeet Singh, Kaur Maninder, Silakari Om
Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
Bioorg Med Chem. 2015 Jul 1;23(13):2953-74. doi: 10.1016/j.bmc.2015.03.071. Epub 2015 Apr 4.
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.
噻唑烷 - 2,4 - 二酮是一种经过广泛探索的杂环核心,用于设计涉及多种病理生理状况的新型药物,即糖尿病、糖尿病并发症、癌症、关节炎、炎症、微生物感染和黑色素瘤等。由于高通量筛选持续产生令人失望的结果,当前的药物开发模式已转向基于结构的药物设计。通过研究配体与其受体蛋白的相互作用,可以缩小从发现活性分子到确定药物之间的差距。因此,了解特定蛋白质靶点与已开发配体之间的分子水平相互作用总是非常有益的;因为这些信息可用于设计与蛋白质契合度更高的新分子。因此,考虑到这一方面,我们证实了有关噻唑烷 - 2,4 - 二酮(TZD)衍生物分子(靶点)水平应用的信息,这些衍生物具有治疗应用,如但不限于抗糖尿病(格列酮类)、抗癌、抗关节炎、抗炎、抗氧化和抗微生物等。TZD衍生物针对各种蛋白质靶点的基于结构的构效关系将作为改变现有配体以设计具有更好结合相互作用的新配体的基准。