N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure–Activity Relationship Studies
The era of chemotherapy began in the 1940s, which is the basis of traditional antitumor approaches and, being one of the most high-tech treatment methods, is still widely used to treat various types of cancer. A promising direction in modern medicinal chemistry is currently the creation of hybrid mo...
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2024-11-01
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| Online Access: | https://www.mdpi.com/1420-3049/29/22/5360 |
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| author | Yulia R. Aleksandrova Natalia S. Nikolaeva Inna A. Shagina Karina D. Smirnova Alla A. Zubishina Alexander I. Khlopotinin Artem N. Fakhrutdinov Alexander L. Khokhlov Roman S. Begunov Margarita E. Neganova |
| author_facet | Yulia R. Aleksandrova Natalia S. Nikolaeva Inna A. Shagina Karina D. Smirnova Alla A. Zubishina Alexander I. Khlopotinin Artem N. Fakhrutdinov Alexander L. Khokhlov Roman S. Begunov Margarita E. Neganova |
| author_sort | Yulia R. Aleksandrova |
| collection | DOAJ |
| description | The era of chemotherapy began in the 1940s, which is the basis of traditional antitumor approaches and, being one of the most high-tech treatment methods, is still widely used to treat various types of cancer. A promising direction in modern medicinal chemistry is currently the creation of hybrid molecules containing several pharmacophore fragments of different structures. This strategy is successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce side effects. In this work, we synthesized 10 1-aryl derivatives of benzimidazole and benzotriazole and 11 hybrids based on them. Among the compounds obtained, the most promising hybrid molecules were diphenylamines, containing an amino group and a benzotriazole cycle in the <i>ortho</i> position to the bridging NH group, which showed significant cytotoxic activity, excellent antioxidant properties and the ability to suppress the migration activity of tumor cells. Taken together, our results demonstrate that substituted diphenylamine-based bipharmacophoric compounds may serve as a promising platform for further optimization to obtain effective antitumor compounds. |
| format | Article |
| id | doaj-art-4e19b94b8d9540198e0285d42a8652d3 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-4e19b94b8d9540198e0285d42a8652d32024-11-26T18:15:41ZengMDPI AGMolecules1420-30492024-11-012922536010.3390/molecules29225360N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure–Activity Relationship StudiesYulia R. Aleksandrova0Natalia S. Nikolaeva1Inna A. Shagina2Karina D. Smirnova3Alla A. Zubishina4Alexander I. Khlopotinin5Artem N. Fakhrutdinov6Alexander L. Khokhlov7Roman S. Begunov8Margarita E. Neganova9Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow 119991, RussiaInstitute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, RussiaNesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow 119991, RussiaFaculty of Biology and Ecology, P. G. Demidov Yaroslavl State University, Yaroslavl 150003, RussiaFaculty of Biology and Ecology, P. G. Demidov Yaroslavl State University, Yaroslavl 150003, RussiaFaculty of Biology and Ecology, P. G. Demidov Yaroslavl State University, Yaroslavl 150003, RussiaN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, RussiaInstitute of Pharmacy, Yaroslavl State Medical University of the Ministry of Health of the Russian Federation, Yaroslavl 150000, RussiaFaculty of Biology and Ecology, P. G. Demidov Yaroslavl State University, Yaroslavl 150003, RussiaNesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow 119991, RussiaThe era of chemotherapy began in the 1940s, which is the basis of traditional antitumor approaches and, being one of the most high-tech treatment methods, is still widely used to treat various types of cancer. A promising direction in modern medicinal chemistry is currently the creation of hybrid molecules containing several pharmacophore fragments of different structures. This strategy is successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce side effects. In this work, we synthesized 10 1-aryl derivatives of benzimidazole and benzotriazole and 11 hybrids based on them. Among the compounds obtained, the most promising hybrid molecules were diphenylamines, containing an amino group and a benzotriazole cycle in the <i>ortho</i> position to the bridging NH group, which showed significant cytotoxic activity, excellent antioxidant properties and the ability to suppress the migration activity of tumor cells. Taken together, our results demonstrate that substituted diphenylamine-based bipharmacophoric compounds may serve as a promising platform for further optimization to obtain effective antitumor compounds.https://www.mdpi.com/1420-3049/29/22/5360hybrid moleculesheterocyclesbenzimidazolesbenzotriazolesdiphenylaminesanticancer agents |
| spellingShingle | Yulia R. Aleksandrova Natalia S. Nikolaeva Inna A. Shagina Karina D. Smirnova Alla A. Zubishina Alexander I. Khlopotinin Artem N. Fakhrutdinov Alexander L. Khokhlov Roman S. Begunov Margarita E. Neganova N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure–Activity Relationship Studies Molecules hybrid molecules heterocycles benzimidazoles benzotriazoles diphenylamines anticancer agents |
| title | N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure–Activity Relationship Studies |
| title_full | N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure–Activity Relationship Studies |
| title_fullStr | N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure–Activity Relationship Studies |
| title_full_unstemmed | N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure–Activity Relationship Studies |
| title_short | N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure–Activity Relationship Studies |
| title_sort | n aryl benzimidazole and benzotriazole derivatives and their hybrids as cytotoxic agents design synthesis and structure activity relationship studies |
| topic | hybrid molecules heterocycles benzimidazoles benzotriazoles diphenylamines anticancer agents |
| url | https://www.mdpi.com/1420-3049/29/22/5360 |
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