Cucumis melo compounds: A new avenue for ALR-2 inhibition in diabetes mellitus
Khalid Alshaghdali,
Munazzah Tasleem,
Raja Rezgui,
Talal Alharazi,
Tolgahan Acar,
Raed Fahad Aljerwan,
Ahmed Altayyar,
Samra Siddiqui,
Mohd Saeed,
Dharmendra Kumar Yadav,
Amir Saeed
Affiliations
Khalid Alshaghdali
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia
Munazzah Tasleem
Department of Biochemistry, Jamia Hamdard, Delhi, India
Raja Rezgui
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia
Talal Alharazi
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia; Department of Medical Microbiology and Immunology, Faculty of Medicine and Health Sciences, Taiz University, Taiz, Yemen
Tolgahan Acar
Department of Physical Therapy, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia
Raed Fahad Aljerwan
Regional Laboratory, Ministry of Health, Hail, Saudi Arabia
Ahmed Altayyar
Regional Laboratory, Ministry of Health, Hail, Saudi Arabia
Samra Siddiqui
Department of Health Service Management, College of Public Health and Health Informatics, University of Hail, Hail, Saudi Arabia
Mohd Saeed
Department of Biology, College of Sciences, University of Hail, Hail, Saudi Arabia; Centre for Global Health Research Saveetha Medical College Chennai - 602105, Tamil Nadu India; Corresponding author. Department of Biology, College of Sciences, University of Hail, Hail, Saudi Arabia.
Dharmendra Kumar Yadav
College of Pharmacy, Gachon University of Medicine and Science, Hambakmoeiro, Yeonsugu, Incheon City, 21924, South Korea; Corresponding author.
Amir Saeed
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia; Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Medical Science & Technology, Khartoum, Sudan
Diabetes mellitus (DM) is a prominent contributor to morbidity and mortality in developed nations, primarily attributable to vascular complications such as atherothrombosis occurring in the coronary arteries. Aldose reductase (ALR2), the main enzyme in the polyol pathway, catalyzes the conversion of glucose to sorbitol, leading to a significant buildup of reactive oxygen species in different tissues. It is therefore a prime candidate for therapeutic targeting, and extensive study is currently underway to discover novel natural compounds that can inhibit it. Cucumis melo (C. melo) has a long history as a lipid-lowering ethanopharmaceutical plant. In this study, compounds derived from C. melo were computationally evaluated as possible lead candidates. Various computational filtering methods were employed to assess the drug-like properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles of the compounds. The compounds were subsequently addressed to analysis of their interactions, molecular docking, and molecular dynamics simulation studies. When compared to the conventional therapeutic compounds, three compounds exhibited enhanced binding affinity and intra-molecular residue interactions, resulting in increased stability and specificity. Consequently, four potent inhibitors, namely PubChem CIDs 119205, 65373, 6184, and 332427, have been identified. These inhibitors exhibit promising potential as pharmacological targets for the advancement of novel ALR-2 inhibitors.
