Synthesis and Cytotoxic Activity of Combretastatin A-4 and 2,3-Diphenyl-2H-indazole Hybrids
Cancer is the second leading cause of death, after cardiovascular diseases. Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is st...
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| Veröffentlicht in: | Pharmaceuticals (Basel, Switzerland) Switzerland), 2021-08, Vol.14 (8), p.815 |
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| creator | Pérez-Villanueva, Jaime Matadamas-Martínez, Félix Yépez-Mulia, Lilián Pérez-Koldenkova, Vadim Leyte-Lugo, Martha Rodríguez-Villar, Karen Cortés-Benítez, Francisco Macías-Jiménez, Ana Perla González-Sánchez, Ignacio Romero-Velásquez, Ariana Palacios-Espinosa, Juan Francisco Soria-Arteche, Olivia |
| description | Cancer is the second leading cause of death, after cardiovascular diseases. Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2H-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2H-indazole and 2,3-dipheny-2H-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound 5, which resulted even better than the reference drug cisplatin against HeLa and SK-LU-1 cells (IC50 of 0.16 and 6.63 µM, respectively), and it had similar potency to the reference drug imatinib against K562 cells. Additionally, in silico and in vitro studies strongly suggest tubulin as the molecular target for hybrid compound 5. |
| doi_str_mv | 10.3390/ph14080815 |
| format | Article |
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Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2H-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2H-indazole and 2,3-dipheny-2H-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound 5, which resulted even better than the reference drug cisplatin against HeLa and SK-LU-1 cells (IC50 of 0.16 and 6.63 µM, respectively), and it had similar potency to the reference drug imatinib against K562 cells. Additionally, in silico and in vitro studies strongly suggest tubulin as the molecular target for hybrid compound 5.</description><identifier>ISSN: 1424-8247</identifier><identifier>EISSN: 1424-8247</identifier><identifier>DOI: 10.3390/ph14080815</identifier><identifier>PMID: 34451912</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Binding sites ; cancer ; Cancer therapies ; combretastatin A-4 ; cytotoxic activity ; Cytotoxicity ; hybrid compounds ; indazole ; Leukemia ; Lung cancer ; Mass spectrometry ; NMR ; Nuclear magnetic resonance ; Scientific imaging</subject><ispartof>Pharmaceuticals (Basel, Switzerland), 2021-08, Vol.14 (8), p.815</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2H-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2H-indazole and 2,3-dipheny-2H-indazole derivatives under microwave irradiation were implemented. 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| subjects | Binding sites cancer Cancer therapies combretastatin A-4 cytotoxic activity Cytotoxicity hybrid compounds indazole Leukemia Lung cancer Mass spectrometry NMR Nuclear magnetic resonance Scientific imaging |
| title | Synthesis and Cytotoxic Activity of Combretastatin A-4 and 2,3-Diphenyl-2H-indazole Hybrids |
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