Abstract
A QSAR study on thiophenyl derivatives as SGLT2 inhibitors as potential antidiabetic agents was performed with thirty-three compounds. Comparison of the obtained results indicated the superiority of the genetic algorithm over the simulated annealing and stepwise forward-backward variable method for feature selection. The best 2D QSAR model showed satisfactory statistical parameters for the data set (r 2 = 0.8499, q 2 = 0.8267, and pred_r 2 = 0.7729) with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution position improves the inhibitory activity. The good predictive 3D-QSAR models by k-nearest neighbor (kNN) method for molecular field analysis (MFA) have cross-validated coefficient q 2 value of 0.7663 and predicted r 2 value of 0.7386. The results have showed that thiophenyl groups are necessary for activity and halogen, bulky, and less bulky groups in thiophenyl nucleus enhanced the biological activity. These studies are promising for the development of novel SGLT2 inhibitor, which may have potent antidiabetic activity.
Highlights
One of the main features of diabetes is the elevation of blood sugar with its deleterious consequences in a variety of tissues [1]
Quantitative structure-activity relationship (QSAR) study was performed on thiophenyl C-aryl glucoside derivatives for their Sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors as potential antidiabetic agents
Genetic algorithm-PLS model indicates the positive contribution of SsCH3count, and SaaSE-index showed that increase in the values of these descriptors is beneficial for the SGLT2 inhibitors
Summary
One of the main features of diabetes is the elevation of blood sugar with its deleterious consequences in a variety of tissues [1]. The idea that affecting glucose absorption in the intestine and/or the glucose reabsorption in the kidney might be a possible way to control the sugar level has evolved. Much attention has been given to sodium-dependent glucose cotransporters (SGLTs), mediators of reabsorption of glucose in the human body. Sodium-dependent glucose cotransporter 2 (SGLT2) is a high-capacity, low-affinity transporter expressed selectively in the S1 domain of the proximal tubule in the kidney and is responsible for 90% of renal glucose reuptake. Sodium dependent glucose cotransporter 1 (SGLT1), on the other hand, is a low-capacity, high-affinity transporter distributed in the kidney, gut, and other tissues, responsible for the remaining 10% of glucose reuptake [8]. Sodium-dependent glucose cotransporters (SGLTs), mediators of reabsorption of glucose in the kidney, have recently emerged as novel drug targets for the treatment of diabetes [9].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
