Thiazole–Thiadiazole Compounds for Enzymatic Modulation and Therapeutic Targeting in Diabetes Mellitus
Shoaib Ahmed Khana b✉, Tayyiaba Iqbala b, Sobhi M. Gomhac d, Magdi E. A. Zakie f, Imed Boukhrisg h, Ali El‐Rayyesi j, Eman A. Alzahranik l, Hamdy Kashtohm n✉
- aDepartment of Chemistry Abbottabad University of Science and Technology Abbottabad Pakistan
- bDepartment of Chemistry, Abbottabad University of Science and Technology, Abbottabad, Pakistan
- cDepartment of Chemistry, Faculty of Science Islamic University of Madinah Madinah Saudi Arabia
- dDepartment of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, Saudi Arabia
- eDepartment of Chemistry, Faculty of Science Imam Mohammad Ibn Saud Islamic University (IMSIU) Riyadh Saudi Arabia
- fDepartment of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
- gDepartment of Physics, Faculty of Science King Khalid University Abha Saudi Arabia
- hDepartment of Physics, Faculty of Science, King Khalid University, Abha, Saudi Arabia
- iCenter For Scientific Research and Entrepreneurship Northern Border University Arar Saudi Arabia
- jCenter For Scientific Research and Entrepreneurship, Northern Border University, Arar, Saudi Arabia
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Abstract
ABSTRACT One of the most significant problems facing the scientific community in the 21st century is diabetes mellitus. There is an urgent need to create new powerful compounds that can fight this terrible disease because the number of instances of diabetes and drug‐resistant diabetes is rising. We have synthesized a novel series of thiazole‐derived thiadiazole‐based Schiff base derivatives ( 1 – 10 ) in an effort to identify potential antidiabetic agents. The structures of these compounds were elucidated using a variety of analytical techniques, including 1 H NMR, 13 C NMR, and HREI–MS. The compounds inhibitory potential against diabetes mellitus was contrasted with that of acarbose, the reference drug. When compared to the reference medication acarbose with IC 50 = 7.50 ± 0.10 and 7.80 ± 0.30 µM, analog 8 (IC 50 = 4.20 ± 0.10 and 4.80 ± 0.60 µM), analog 5 (IC 50 = 5.10 ± 0.30 and 5.60±0.30 µM), and analog 9 (IC 50 = 6.20 ± 0.10 and 6.90 ± 0.10 µM) appeared as the most promising inhibitor in this regard. These compounds pharmacological profiles were further investigated by employing molecular docking studies to assess the bonding interactions between ligands and enzymes, whereas dynamic simulations were used to analyze the structural variations and conformational changes of the protein complex. Potent scaffold nontoxic nature was demonstrated by ADMET analysis, which supports their usage as a treatment in the future. Furthermore, DFT analyses provided the charge distribution of the compounds that drive chemical reactivity and enzyme interactions.
TL;DRA novel series of thiazole‐derived thiadiazole‐based Schiff base derivatives is synthesized in an effort to identify potential antidiabetic agents and Potent scaffold nontoxic nature was demonstrated by ADMET analysis, which supports their usage as a treatment in the future. (Semantic Scholar)