Effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl) acetamide
Diabetes is a prevalent disease in South India, posing a severe threat to public health. To tackle this issue, researchers are focusing on developing multi-targeted ligands, and one promising candidate is (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (DMDA)...
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Elsevier
2024-12-01
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| Series: | Chemical Physics Impact |
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| author | Arubiya J S.J. Jenepha Mary V. Shally Mohd Usman Mohd Siddique J. Deva Anban |
| author_facet | Arubiya J S.J. Jenepha Mary V. Shally Mohd Usman Mohd Siddique J. Deva Anban |
| author_sort | Arubiya J |
| collection | DOAJ |
| description | Diabetes is a prevalent disease in South India, posing a severe threat to public health. To tackle this issue, researchers are focusing on developing multi-targeted ligands, and one promising candidate is (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (DMDA). Geometry optimization of DMDA was carried out using density functional theory with 6–311+G(d, p) basis set to develop a theoretical model close to the previously synthesized and reported DMDA. Natural Bond Orbital analysis was conducted to scrutinize the phenomena of charge delocalization and electronic exchange interactions governing both intermolecular and intramolecular associations. Moreover, the vibrational characteristics of the molecule were elucidated through FT-IR and FT-Raman spectra. Lowest Unoccupied Molecular Orbital and Highest Occupied Molecular Orbital have also been explored to enhance understanding of the molecule's electronic structure and reactivity. Hirshfeld surface analysis was utilized to investigate the interactions between molecules within the crystalline lattice. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis elucidates the potential pharmacokinetic profile of DMDA. Molecular docking was performed to predict the binding site responsible for various interactions with the targeted protein. By combining these techniques, a comprehensive molecular description of DMDA has been generated.There are three prominent intramolecular interactions within the ambit of van der Waals radii, leading to stability of the molecule. The presence of a broad and shallow band with a significant red shift provides evidence for the strong intermolecular OH hydrogen bonding. DMDA complies with Lipinski's Rule of Five, highlighting its favorable characteristics for pharmaceutical efficacy. The negative binding energies determined by docking studies ascertain the potential sites of ligand-protein interaction leading to inhibition of α-amylase and α-glucosidase enzyme. |
| format | Article |
| id | doaj-art-7470e33ac49d4ae2b60242962e5b7285 |
| institution | DOAJ |
| issn | 2667-0224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj-art-7470e33ac49d4ae2b60242962e5b72852025-08-20T02:48:39ZengElsevierChemical Physics Impact2667-02242024-12-01910065910.1016/j.chphi.2024.100659Effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl) acetamideArubiya J0S.J. Jenepha Mary1V. Shally2Mohd Usman Mohd Siddique3J. Deva Anban4PG & Research Department of Physics, Holy Cross College (Autonomous), Nagercoil – Reg. No. 21113042132013 Affiliated to Manonmanium Sundaranar University, Tirunelveli, IndiaPG & Research Department of Physics, Holy Cross College (Autonomous), Nagercoil – Reg. No. 21113042132013 Affiliated to Manonmanium Sundaranar University, Tirunelveli, IndiaPG & Research Department of Physics, Holy Cross College (Autonomous), Nagercoil – Reg. No. 21113042132013 Affiliated to Manonmanium Sundaranar University, Tirunelveli, IndiaDepartment of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, Maharashtra, IndiaDepartment of Physics, Pioneer Kumaraswamy College, Nagercoil, India; Corresponding author at: Department of Physics, Pioneer Kumaraswamy College, Nagercoil 629003, India.Diabetes is a prevalent disease in South India, posing a severe threat to public health. To tackle this issue, researchers are focusing on developing multi-targeted ligands, and one promising candidate is (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (DMDA). Geometry optimization of DMDA was carried out using density functional theory with 6–311+G(d, p) basis set to develop a theoretical model close to the previously synthesized and reported DMDA. Natural Bond Orbital analysis was conducted to scrutinize the phenomena of charge delocalization and electronic exchange interactions governing both intermolecular and intramolecular associations. Moreover, the vibrational characteristics of the molecule were elucidated through FT-IR and FT-Raman spectra. Lowest Unoccupied Molecular Orbital and Highest Occupied Molecular Orbital have also been explored to enhance understanding of the molecule's electronic structure and reactivity. Hirshfeld surface analysis was utilized to investigate the interactions between molecules within the crystalline lattice. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis elucidates the potential pharmacokinetic profile of DMDA. Molecular docking was performed to predict the binding site responsible for various interactions with the targeted protein. By combining these techniques, a comprehensive molecular description of DMDA has been generated.There are three prominent intramolecular interactions within the ambit of van der Waals radii, leading to stability of the molecule. The presence of a broad and shallow band with a significant red shift provides evidence for the strong intermolecular OH hydrogen bonding. DMDA complies with Lipinski's Rule of Five, highlighting its favorable characteristics for pharmaceutical efficacy. The negative binding energies determined by docking studies ascertain the potential sites of ligand-protein interaction leading to inhibition of α-amylase and α-glucosidase enzyme.http://www.sciencedirect.com/science/article/pii/S2667022424002032NBONCAHOMO-LUMOHirshfeld surface analysisADMETAnti-diabetic |
| spellingShingle | Arubiya J S.J. Jenepha Mary V. Shally Mohd Usman Mohd Siddique J. Deva Anban Effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl) acetamide Chemical Physics Impact NBO NCA HOMO-LUMO Hirshfeld surface analysis ADMET Anti-diabetic |
| title | Effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl) acetamide |
| title_full | Effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl) acetamide |
| title_fullStr | Effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl) acetamide |
| title_full_unstemmed | Effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl) acetamide |
| title_short | Effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl) acetamide |
| title_sort | effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent e n n diethyl 2 5 3 hydroxy 4 methoxybenzylidene 2 4 dioxothiazolidin 3 yl acetamide |
| topic | NBO NCA HOMO-LUMO Hirshfeld surface analysis ADMET Anti-diabetic |
| url | http://www.sciencedirect.com/science/article/pii/S2667022424002032 |
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