Title
Insights from the molecular docking analysis of SGLT2 and FIMH to combat uropathogenicity
Authors
Wesam H Abdulaal1, 2, Muhammed A Bakhrebah3, Majed S Nassar3*, Ibrahim Abdullah Almazni4, Wael Abdullah Almutairi5, Zuhair S Natto6 & Amin K Khattab7
Affiliation
1Department of Biochemistry, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 2Centre for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 3Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST) Riyadh 1144, Saudi Arabia; 4Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, P.O. Box 1988, Najran 61441, Saudi Arabia; 5Department of Respiratory Services, Ministry of National Guard Hospital and Health Affairs (MNGHA) P.O. box 22490, kingdom of Saudi Arabia; 6Department of Dental Public Health, Faculty of Dentistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 7Quality and Outcome Control Management, General Directorate of Health Affairs-Madina Region, Ministry of Health, Madina 32000, Saudi Arabia; *Corresponding author
Majed S Nassar - E-mail: nassarbiotech@gmail.com and mnassar@kacst.edu.sa
Article Type
Research Article
Date
Received November 1, 2022; Revised November 29, 2022; Accepted November 30, 2022, Published November 30, 2022
Abstract
SGLT2 inhibitors are a novel class of FDA approved anti-diabetes drugs. They act by blocking the SGLT2 protein, which prevents glucose reabsorption, leading in enhance glucose excretion and lower blood glucose levels. In diabetic patients, SGLT2 inhibitors have been linked to urinary tract infections (UTIs). Therefore, the development of novel SGLT2 inhibitors with no adverse effects is a need of time. With this purpose, in this study, 48164natural compounds from ZINC database were screened targeting both the SGLT2 and FimH protein using insilico approaches. FimH has been discovered as a promising target for preventing and treating UTIs. The hit compounds ZINC69481892, ZINC1612996, and ZINC4039265 exhibited strong binding with both SGLT2 and FimH with binding energies values of −9.88, −8.96, and −10.57 kcal/mol for SGLT2, and −7.86, −7.01, and −8.92 kcal/mol for FimH, which is higher than that of controls (−6.78 kcal/mol (Empaglifozolin for SGLT2) and −5.14 kcal/mol (Heptyl α-d-mannopyranoside for FimH)). Hits were found to bind with key residues of both SGLT2 and FimH protein. In addition, physiochemical properties showed that these compounds have good drug-likeness properties. Therefore, we anticipate that if these compounds are investigated further, might be potential SGLT2 inhibitors with less uropathogenic adverse effects.
Keywords
SGLT2 inhibitors, urinary tract infections, FimH, natural compounds
Citation
Abdulaal et al. Bioinformation 18(11): 1044-1049 (2022)
Edited by
P Kangueane
ISSN
0973-2063
Publisher
License
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
