Structural tailoring of etoricoxib: A spectrochemical, medicinal and pharmacological study
Etoricoxib (ETC), a selective cyclooxygenase enzyme (COX-2) inhibitor, is widely utilized to manage pain and inflammation. Nevertheless, its therapeutic efficacy is limited by poor aqueous solubility, low bioavailability, and significant cardiovascular risks, including increased blood pressure, thro...
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Elsevier
2025-06-01
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| Series: | Chemical Physics Impact |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667022425000180 |
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| author | Bakul Akter Silvia Aishee Abdullah Hridoy Md. Mehedi Hasan Pulok Mohammad Ariful Islam Antu Biswas Aurna Patwary Majedul Hoque MD. Sazidul Islam Md. Nipatul Hasan Nirob Faisal Islam Chowdhury Monir Uzzaman |
| author_facet | Bakul Akter Silvia Aishee Abdullah Hridoy Md. Mehedi Hasan Pulok Mohammad Ariful Islam Antu Biswas Aurna Patwary Majedul Hoque MD. Sazidul Islam Md. Nipatul Hasan Nirob Faisal Islam Chowdhury Monir Uzzaman |
| author_sort | Bakul Akter |
| collection | DOAJ |
| description | Etoricoxib (ETC), a selective cyclooxygenase enzyme (COX-2) inhibitor, is widely utilized to manage pain and inflammation. Nevertheless, its therapeutic efficacy is limited by poor aqueous solubility, low bioavailability, and significant cardiovascular risks, including increased blood pressure, thrombosis, and the potential for myocardial infarction. This study aimed to address these limitations through structural modifications of etoricoxib. A total of 21 derivatives were designed by introducing various functioning sets at the R3, R2, and R1 sites of ETC. Quantum chemical calculations were performed to assess alterations in physicochemical properties, such as HOMO–LUMO energy gaps, electrostatic potential, enthalpy, and dipole moments. Notably, most of the derivatives showed improved binding affinities, particularly ETC9 and ETC19, demonstrating the highest binding interactions in molecular docking studies (-10.1 and -10.8 kcal/mol, respectively). Furthermore, molecular dynamics (MD) simulations accomplished by exploiting the YASARA dynamics software program with the AMBER14 energy field throughout 100 ns revealed that the ETC9 and ETC19 derivatives exhibited enhanced stability and flexibility profiles compared to the parent drug, ETC. ADMET and PASS predictions confirmed the drug-like properties of most derivatives, particularly ETC19 and ETC9, which also showed improved absorption, better blood-brain barrier penetration, and reduced toxicity. These outcomes underscore the prospect of the de novo-designed etoricoxib analogues as safer and more effective alternatives, effectively addressing the pharmacological limitations and safety concerns associated with the parent drug. |
| format | Article |
| id | doaj-art-0041fbb56acd4af481cba201d55629ac |
| institution | Kabale University |
| issn | 2667-0224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj-art-0041fbb56acd4af481cba201d55629ac2025-01-29T05:02:19ZengElsevierChemical Physics Impact2667-02242025-06-0110100830Structural tailoring of etoricoxib: A spectrochemical, medicinal and pharmacological studyBakul Akter0Silvia Aishee1Abdullah Hridoy2Md. Mehedi Hasan Pulok3Mohammad Ariful Islam4Antu Biswas5Aurna Patwary6Majedul Hoque7MD. Sazidul Islam8Md. Nipatul Hasan Nirob9Faisal Islam Chowdhury10Monir Uzzaman11Faculty of Biological Science, Department of Pharmacy, University of Chittagong, Chittagong, 4331, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshDepartment of Chemistry, University of Dhaka, Dhaka, 1000, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshDepartment of Chemistry, Bhawal Badre Alam Govt. College, National University, Gazipur, 1704, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshDepartment of Pharmacy, Jahangirnagar University, Dhaka, 1342, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshFaculty of Science, Department of Biochemistry and Molecular Biology, University of Noakhali Science and Technology, Noakhali, 3814, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshDepartment of Theoretical and Computational Chemistry, University of Dhaka, Dhaka, 1000, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshDepartment of Chemistry, Feni Govt. College, Feni, 3900, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshDepartment of Pharmacy, Jahangirnagar University, Dhaka, 1342, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshDepartment of Pharmacy, Jahangirnagar University, Dhaka, 1342, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshDepartment of Pharmacy, Jahangirnagar University, Dhaka, 1342, Bangladesh; Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, BangladeshDepartment of Chemistry, University of Chittagong, Chittagong, 4331, Bangladesh; Corresponding authors at: Graduate School of Engineering, Department of Applied Chemistry, Mie University, Tsu 541-8507, Mie, Japan.Drug Design Division, Computer in Chemistry and Medicine Laboratory, Dhaka, Bangladesh; Department of Chemistry, University of Chittagong, Chittagong, 4331, Bangladesh; Department of Applied Chemistry, Graduate School of Engineering, Mie University, Tsu 514-8507, Mie, Japan; Corresponding authors at: Graduate School of Engineering, Department of Applied Chemistry, Mie University, Tsu 541-8507, Mie, Japan.Etoricoxib (ETC), a selective cyclooxygenase enzyme (COX-2) inhibitor, is widely utilized to manage pain and inflammation. Nevertheless, its therapeutic efficacy is limited by poor aqueous solubility, low bioavailability, and significant cardiovascular risks, including increased blood pressure, thrombosis, and the potential for myocardial infarction. This study aimed to address these limitations through structural modifications of etoricoxib. A total of 21 derivatives were designed by introducing various functioning sets at the R3, R2, and R1 sites of ETC. Quantum chemical calculations were performed to assess alterations in physicochemical properties, such as HOMO–LUMO energy gaps, electrostatic potential, enthalpy, and dipole moments. Notably, most of the derivatives showed improved binding affinities, particularly ETC9 and ETC19, demonstrating the highest binding interactions in molecular docking studies (-10.1 and -10.8 kcal/mol, respectively). Furthermore, molecular dynamics (MD) simulations accomplished by exploiting the YASARA dynamics software program with the AMBER14 energy field throughout 100 ns revealed that the ETC9 and ETC19 derivatives exhibited enhanced stability and flexibility profiles compared to the parent drug, ETC. ADMET and PASS predictions confirmed the drug-like properties of most derivatives, particularly ETC19 and ETC9, which also showed improved absorption, better blood-brain barrier penetration, and reduced toxicity. These outcomes underscore the prospect of the de novo-designed etoricoxib analogues as safer and more effective alternatives, effectively addressing the pharmacological limitations and safety concerns associated with the parent drug.http://www.sciencedirect.com/science/article/pii/S2667022425000180EtoricoxibPhysicochemicalMolecular Dynamics simulationMolecular dockingADMETPASS |
| spellingShingle | Bakul Akter Silvia Aishee Abdullah Hridoy Md. Mehedi Hasan Pulok Mohammad Ariful Islam Antu Biswas Aurna Patwary Majedul Hoque MD. Sazidul Islam Md. Nipatul Hasan Nirob Faisal Islam Chowdhury Monir Uzzaman Structural tailoring of etoricoxib: A spectrochemical, medicinal and pharmacological study Chemical Physics Impact Etoricoxib Physicochemical Molecular Dynamics simulation Molecular docking ADMET PASS |
| title | Structural tailoring of etoricoxib: A spectrochemical, medicinal and pharmacological study |
| title_full | Structural tailoring of etoricoxib: A spectrochemical, medicinal and pharmacological study |
| title_fullStr | Structural tailoring of etoricoxib: A spectrochemical, medicinal and pharmacological study |
| title_full_unstemmed | Structural tailoring of etoricoxib: A spectrochemical, medicinal and pharmacological study |
| title_short | Structural tailoring of etoricoxib: A spectrochemical, medicinal and pharmacological study |
| title_sort | structural tailoring of etoricoxib a spectrochemical medicinal and pharmacological study |
| topic | Etoricoxib Physicochemical Molecular Dynamics simulation Molecular docking ADMET PASS |
| url | http://www.sciencedirect.com/science/article/pii/S2667022425000180 |
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