Design, synthesis, structural characterization, in vitro anticancer activity, and in silico studies of some new hydroxylated and fluorinated-substituted hydrazone derivatives
Today, due to improved lifestyles and increased survival, the number of new cancer cases and cancer-related deaths continues to increase. In this study, novel hydroxylated and fluorinated-substituted hydrazone derivatives bearing an aromatic nitro moiety (2a-d and 3a-d) were designed as potential an...
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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/S2667022425000179 |
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| author | Reşit Çakmak Eyüp Başaran Ömer Erdoğan Suraj N. Mali Semiha Köprü Haya Yasin Shailesh S. Gurav Giray Topal |
| author_facet | Reşit Çakmak Eyüp Başaran Ömer Erdoğan Suraj N. Mali Semiha Köprü Haya Yasin Shailesh S. Gurav Giray Topal |
| author_sort | Reşit Çakmak |
| collection | DOAJ |
| description | Today, due to improved lifestyles and increased survival, the number of new cancer cases and cancer-related deaths continues to increase. In this study, novel hydroxylated and fluorinated-substituted hydrazone derivatives bearing an aromatic nitro moiety (2a-d and 3a-d) were designed as potential anticancer drug candidates, synthesized for the first time, and evaluated for their anticancer activity against chondrosarcoma (SW1353), a common primary malignant cartilage-forming tumor, neuroblastoma (SH-SY5Y), a type of brain cancer, and healthy (L929) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method for 24 h. The chemical structures of the target molecules were confirmed by FT-IR, 1D NMR (1H- and 13C- NMR, and APT), 2D NMR (COSY, HETCOR, and HMBC), and elemental analysis. Some of the compounds targeted against these cancer cell lines showed activity greater than 200 μM, whereas others (2d and 3a) demonstrated significant cytotoxic activity. Among them, compound 3a (IC50 = 9.45 ± 2.14 μM), a fluorinated-substituted hydrazone derivative, showed significant cytotoxic activity against the human SW1353 cell line compared to cisplatin (IC50 = 11.9 ± 0.95 μM). The anti-migratory properties of compounds 2d and 3a in SW1353 cells, were investigated. In particular, compound 3a exhibited anti-migration behavior in SW1353 cells, with a wound closure rate of 22.25 % compared with control cells. Further, scaffolds 2d and 3a exhibited the best docking with target receptor proteins 2OH4 (−8.3 and −8.4 kcal/mol) and 3QX3 (−12.2 and 11.0 kcal/mol), thereby supporting our bioactivity studies. Compounds 2a, 3a, 3b, and 3c showed high gastrointestinal (GI) absorption, with all except 3a being non-permeable to the blood-brain barrier (BBB). Most compounds, except 3d, are non-substrates of P-glycoprotein (P-gp). In conclusion, the in vitro and in silico results of some of the tested compounds indicate that they could be promising molecular frameworks for further studies. |
| format | Article |
| id | doaj-art-9c33761aed5d49a187c1664b88603b1b |
| institution | Kabale University |
| issn | 2667-0224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj-art-9c33761aed5d49a187c1664b88603b1b2025-01-23T05:27:53ZengElsevierChemical Physics Impact2667-02242025-06-0110100829Design, synthesis, structural characterization, in vitro anticancer activity, and in silico studies of some new hydroxylated and fluorinated-substituted hydrazone derivativesReşit Çakmak0Eyüp Başaran1Ömer Erdoğan2Suraj N. Mali3Semiha Köprü4Haya Yasin5Shailesh S. Gurav6Giray Topal7Medical Laboratory Techniques Program, Vocational School of Health Services, Batman University, Batman, Türkiye; Corresponding authors.Department of Chemistry and Chemical Processing Technologies, Vocational School of Technical Sciences, Batman University, Batman, Türkiye; Corresponding authors.Department of Biochemistry, School of Medicine, Gaziantep Islamic Science and Technology University, Gaziantep, TürkiyeSchool of Pharmacy, D. Y. Patil University (Deemed to be University), Navi Mumbai, Maharashtra, IndiaDepartment of Chemistry, Faculty of Sciences, Erciyes University, Kayseri, TürkiyeDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirate; Center of Medical and Bio-allied Health Sciences Research, Ajman University, P O Box 346, Ajman, United Arab Emirates; Corresponding authors.Department of Chemistry, VIVA College, Virar (W), Maharashtra 401303, IndiaDepartment of Chemistry, Ziya Gökalp Faculty of Education, Dicle University, Diyarbakır, TürkiyeToday, due to improved lifestyles and increased survival, the number of new cancer cases and cancer-related deaths continues to increase. In this study, novel hydroxylated and fluorinated-substituted hydrazone derivatives bearing an aromatic nitro moiety (2a-d and 3a-d) were designed as potential anticancer drug candidates, synthesized for the first time, and evaluated for their anticancer activity against chondrosarcoma (SW1353), a common primary malignant cartilage-forming tumor, neuroblastoma (SH-SY5Y), a type of brain cancer, and healthy (L929) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method for 24 h. The chemical structures of the target molecules were confirmed by FT-IR, 1D NMR (1H- and 13C- NMR, and APT), 2D NMR (COSY, HETCOR, and HMBC), and elemental analysis. Some of the compounds targeted against these cancer cell lines showed activity greater than 200 μM, whereas others (2d and 3a) demonstrated significant cytotoxic activity. Among them, compound 3a (IC50 = 9.45 ± 2.14 μM), a fluorinated-substituted hydrazone derivative, showed significant cytotoxic activity against the human SW1353 cell line compared to cisplatin (IC50 = 11.9 ± 0.95 μM). The anti-migratory properties of compounds 2d and 3a in SW1353 cells, were investigated. In particular, compound 3a exhibited anti-migration behavior in SW1353 cells, with a wound closure rate of 22.25 % compared with control cells. Further, scaffolds 2d and 3a exhibited the best docking with target receptor proteins 2OH4 (−8.3 and −8.4 kcal/mol) and 3QX3 (−12.2 and 11.0 kcal/mol), thereby supporting our bioactivity studies. Compounds 2a, 3a, 3b, and 3c showed high gastrointestinal (GI) absorption, with all except 3a being non-permeable to the blood-brain barrier (BBB). Most compounds, except 3d, are non-substrates of P-glycoprotein (P-gp). In conclusion, the in vitro and in silico results of some of the tested compounds indicate that they could be promising molecular frameworks for further studies.http://www.sciencedirect.com/science/article/pii/S2667022425000179AcylhydrazoneCytotoxic activityMolecular dockingADME profile |
| spellingShingle | Reşit Çakmak Eyüp Başaran Ömer Erdoğan Suraj N. Mali Semiha Köprü Haya Yasin Shailesh S. Gurav Giray Topal Design, synthesis, structural characterization, in vitro anticancer activity, and in silico studies of some new hydroxylated and fluorinated-substituted hydrazone derivatives Chemical Physics Impact Acylhydrazone Cytotoxic activity Molecular docking ADME profile |
| title | Design, synthesis, structural characterization, in vitro anticancer activity, and in silico studies of some new hydroxylated and fluorinated-substituted hydrazone derivatives |
| title_full | Design, synthesis, structural characterization, in vitro anticancer activity, and in silico studies of some new hydroxylated and fluorinated-substituted hydrazone derivatives |
| title_fullStr | Design, synthesis, structural characterization, in vitro anticancer activity, and in silico studies of some new hydroxylated and fluorinated-substituted hydrazone derivatives |
| title_full_unstemmed | Design, synthesis, structural characterization, in vitro anticancer activity, and in silico studies of some new hydroxylated and fluorinated-substituted hydrazone derivatives |
| title_short | Design, synthesis, structural characterization, in vitro anticancer activity, and in silico studies of some new hydroxylated and fluorinated-substituted hydrazone derivatives |
| title_sort | design synthesis structural characterization in vitro anticancer activity and in silico studies of some new hydroxylated and fluorinated substituted hydrazone derivatives |
| topic | Acylhydrazone Cytotoxic activity Molecular docking ADME profile |
| url | http://www.sciencedirect.com/science/article/pii/S2667022425000179 |
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