Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer
Overall, drug design is a dynamic and evolving field, with researchers constantly working to improve their understanding of molecular interactions, develop new computational methods, and explore innovative techniques for creating effective and safe medications. The process can involve steps such as...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023085201 |
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| author | Nadeem Abad Fares Hezam Al-Ostoot Sajda Ashraf Karim Chkirate Majed S. Aljohani Hussam Y. Alharbi Shafeek Buhlak Mohamed El Hafi Luc Van Meervelt Basheer M. Al-Maswari El Mokhtar Essassi Youssef Ramli |
| author_facet | Nadeem Abad Fares Hezam Al-Ostoot Sajda Ashraf Karim Chkirate Majed S. Aljohani Hussam Y. Alharbi Shafeek Buhlak Mohamed El Hafi Luc Van Meervelt Basheer M. Al-Maswari El Mokhtar Essassi Youssef Ramli |
| author_sort | Nadeem Abad |
| collection | DOAJ |
| description | Overall, drug design is a dynamic and evolving field, with researchers constantly working to improve their understanding of molecular interactions, develop new computational methods, and explore innovative techniques for creating effective and safe medications. The process can involve steps such as the identification of targets, the discovery of lead compounds, lead optimization, preliminary testing, human trials, regulatory approval and finally post-marketing surveillance, all aimed at bringing a new drug from concept to market. In this article, the synthesis of the novel triazolequinoxalin (TZQ) 1-((1-hexyl-1H-1,2,3-triazol-5-yl)methyl)-3-phenylquinoxalin-2(1H)-one (4) is reported. The structure has been identified with a variety of spectroscopic methods (1H, 13C NMR, and LC-MS) and finally, the structure has been determined by X-ray diffraction (XRD) studies. The TZQ molecule has crystallized in the monoclinic space C2/c group with unit cell dimensions a = 41.201(2) Å, b = 10.6339(6) Å, c = 9.4997(4) Å, β = 93.904(4). The crystal structure is stabilized by intermolecular interactions (N–H ⋯ O and N–H … Cg) occurring within the molecule. The presence of these intermolecular interactions is evaluated through analysis of Hirshfeld surfaces (HS) and two-dimensional (2D) chemical fingerprints map. Additionally, energy frameworks were employed to identify the prevailing interaction energy influencing the molecular arrangement. Density Functional Theory (DFT) calculations were computed to establish concurrence between theoretical and experimental results. Furthermore, the HOMO-LUMO energy levels were determined using the B3LYP/6-31+G(d, p) level of theory. Finally, molecular docking was used to predict the anti-cancer activity of the compound (4) against PFKFB3 kinase and presented noticeable hydrophilic and hydrophobic interactions at the active site region. |
| first_indexed | 2024-03-09T09:20:09Z |
| format | Article |
| id | doaj.art-d08ad8a5e0a542afa15852a08ef0c480 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-09T09:20:09Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-d08ad8a5e0a542afa15852a08ef0c4802023-12-02T07:01:49ZengElsevierHeliyon2405-84402023-11-01911e21312Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancerNadeem Abad0Fares Hezam Al-Ostoot1Sajda Ashraf2Karim Chkirate3Majed S. Aljohani4Hussam Y. Alharbi5Shafeek Buhlak6Mohamed El Hafi7Luc Van Meervelt8Basheer M. Al-Maswari9El Mokhtar Essassi10Youssef Ramli11Department of Biochemistry, Faculty of Education & Science, Al-Baydha University, Yemen; Laboratory of Heterocyclic Organic Chemistry URAC 21, Pharmacochemistry Competence Center, Av. Ibn Battouta, BP 1014, Faculty of Sciences, Mohammed V University in Rabat, 10010, Morocco; Corresponding author. Department of Biochemistry, Faculty of Education & Science, Al-Baydha University, Yemen.Department of Biochemistry, Faculty of Education & Science, Al-Baydha University, Yemen; Corresponding author.Dr.PanjwaniCenter for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanLaboratory of Heterocyclic Organic Chemistry URAC 21, Pharmacochemistry Competence Center, Av. Ibn Battouta, BP 1014, Faculty of Sciences, Mohammed V University in Rabat, 10010, MoroccoDepartment of Chemistry, Faculty of Science, Taibah University, Yanbu, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Taibah University, Yanbu, Saudi ArabiaDepartment of Chemistry, Abantİzzet Baysal University, 14280 Bolu, TurkeyLaboratory of Heterocyclic Organic Chemistry URAC 21, Pharmacochemistry Competence Center, Av. Ibn Battouta, BP 1014, Faculty of Sciences, Mohammed V University in Rabat, 10010, MoroccoLaboratory of Biomolecular Architecture, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Leuven, B-3001, BelgiumDepartment of Chemistry, Yuvaraja's College, University of Mysore, Mysuru, Karnataka 570005, IndiaLaboratory of Heterocyclic Organic Chemistry URAC 21, Pharmacochemistry Competence Center, Av. Ibn Battouta, BP 1014, Faculty of Sciences, Mohammed V University in Rabat, 10010, MoroccoLaboratory of Medicinal Chemistry, Drug Sciences Research Center, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, MoroccoOverall, drug design is a dynamic and evolving field, with researchers constantly working to improve their understanding of molecular interactions, develop new computational methods, and explore innovative techniques for creating effective and safe medications. The process can involve steps such as the identification of targets, the discovery of lead compounds, lead optimization, preliminary testing, human trials, regulatory approval and finally post-marketing surveillance, all aimed at bringing a new drug from concept to market. In this article, the synthesis of the novel triazolequinoxalin (TZQ) 1-((1-hexyl-1H-1,2,3-triazol-5-yl)methyl)-3-phenylquinoxalin-2(1H)-one (4) is reported. The structure has been identified with a variety of spectroscopic methods (1H, 13C NMR, and LC-MS) and finally, the structure has been determined by X-ray diffraction (XRD) studies. The TZQ molecule has crystallized in the monoclinic space C2/c group with unit cell dimensions a = 41.201(2) Å, b = 10.6339(6) Å, c = 9.4997(4) Å, β = 93.904(4). The crystal structure is stabilized by intermolecular interactions (N–H ⋯ O and N–H … Cg) occurring within the molecule. The presence of these intermolecular interactions is evaluated through analysis of Hirshfeld surfaces (HS) and two-dimensional (2D) chemical fingerprints map. Additionally, energy frameworks were employed to identify the prevailing interaction energy influencing the molecular arrangement. Density Functional Theory (DFT) calculations were computed to establish concurrence between theoretical and experimental results. Furthermore, the HOMO-LUMO energy levels were determined using the B3LYP/6-31+G(d, p) level of theory. Finally, molecular docking was used to predict the anti-cancer activity of the compound (4) against PFKFB3 kinase and presented noticeable hydrophilic and hydrophobic interactions at the active site region.http://www.sciencedirect.com/science/article/pii/S2405844023085201TriazolequinoxalinEnergy frameworkHirshfeld surfaceAnti-cancer docking studies |
| spellingShingle | Nadeem Abad Fares Hezam Al-Ostoot Sajda Ashraf Karim Chkirate Majed S. Aljohani Hussam Y. Alharbi Shafeek Buhlak Mohamed El Hafi Luc Van Meervelt Basheer M. Al-Maswari El Mokhtar Essassi Youssef Ramli Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer Heliyon Triazolequinoxalin Energy framework Hirshfeld surface Anti-cancer docking studies |
| title | Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer |
| title_full | Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer |
| title_fullStr | Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer |
| title_full_unstemmed | Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer |
| title_short | Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer |
| title_sort | synthesis crystal structure dft hirshfeld surface analysis energy frameworks and in silico drug targeting pfkfb3 kinase of novel triazolequinoxalin derivative tzq as a therapeutic strategy against cancer |
| topic | Triazolequinoxalin Energy framework Hirshfeld surface Anti-cancer docking studies |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023085201 |
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