Green synthesis and in vitro anticancer evaluation of 1,2-disubstituted benzimidazole derivatives
The benzimidazole core, a fundamental scaffold in medicinal chemistry, has been key in the advancement of this health field, leading to the development of numerous commercially available drugs, including those to treat cancer, which constitutes the most pressing health problem, being the main cause...
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Elsevier
2025-03-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625001171 |
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| author | Alcives Avila-Sorrosa Luis Angel Gil-Ruiz María Elena Vargas-Diaz Benjamín Torres-Nogueda David Morales-Morales |
| author_facet | Alcives Avila-Sorrosa Luis Angel Gil-Ruiz María Elena Vargas-Diaz Benjamín Torres-Nogueda David Morales-Morales |
| author_sort | Alcives Avila-Sorrosa |
| collection | DOAJ |
| description | The benzimidazole core, a fundamental scaffold in medicinal chemistry, has been key in the advancement of this health field, leading to the development of numerous commercially available drugs, including those to treat cancer, which constitutes the most pressing health problem, being the main cause of death globally, whose current chemotherapeutic treatments, although some effective, have serious side effects, highlighting the need to discover safer and more potent drugs. In this context, a series of 1-benzyl-2-aryl benzimidazole derivatives (21‐–29) were synthesized using a selective and affordable method under mild reaction conditions and green chemistry criteria. A hydroxylated Schiff base (23) is also included, evidence of the possible reaction mechanism for synthesizing the different BZM derivatives. All compounds were characterized using spectroscopic techniques and single-crystal X-ray analysis. The latter, including Hirshfeld surface analysis, allowed the study of the main non-covalent interactions that stabilize molecular packing and supramolecular arrangements. A preliminarily evaluated by in vitro assays against a panel of six human cancer cell lines and healthy cells using tamoxifen as a reference drug. The results showed that all the compounds demonstrate bioactivity, highlighting the halogenated structures 1-(4-chlorobenzyl)-2-(4-chlorophenyl)-1H-benzo[d]imidazole (26), 1-(4-bromobenzyl)-2-(4-bromophenyl)-1H-benzo[d]imidazole (27) and 1-(4-methoxybenzyl)-2-(4-methoxyphenyl)-1H-bebioavailability nzo[d]imidazole (29) exhibited the highest biological activity, mainly against the cancer lines leukemia (K562), colon cancer (HCT-15), breast cancer (MCF-7) and lung cancer (SKLU-1). A brief ADME analysis evaluated that the obtained compounds have pharmacodynamic and pharmacokinetic parameters to be potentially administered enterally. |
| format | Article |
| id | doaj-art-1c0ee7a35ccc4b10acdbc6a4b212ed02 |
| institution | OA Journals |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-1c0ee7a35ccc4b10acdbc6a4b212ed022025-08-20T02:04:38ZengElsevierResults in Chemistry2211-71562025-03-011410213410.1016/j.rechem.2025.102134Green synthesis and in vitro anticancer evaluation of 1,2-disubstituted benzimidazole derivativesAlcives Avila-Sorrosa0Luis Angel Gil-Ruiz1María Elena Vargas-Diaz2Benjamín Torres-Nogueda3David Morales-Morales4Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 Ciudad de México, Mexico.; Corresponding author.Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 Ciudad de México, Mexico.Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 Ciudad de México, Mexico.Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Parasitología, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 Ciudad de México, Mexico.; Corresponding author.Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Ciudad de México C.P. 04510, Mexico.The benzimidazole core, a fundamental scaffold in medicinal chemistry, has been key in the advancement of this health field, leading to the development of numerous commercially available drugs, including those to treat cancer, which constitutes the most pressing health problem, being the main cause of death globally, whose current chemotherapeutic treatments, although some effective, have serious side effects, highlighting the need to discover safer and more potent drugs. In this context, a series of 1-benzyl-2-aryl benzimidazole derivatives (21‐–29) were synthesized using a selective and affordable method under mild reaction conditions and green chemistry criteria. A hydroxylated Schiff base (23) is also included, evidence of the possible reaction mechanism for synthesizing the different BZM derivatives. All compounds were characterized using spectroscopic techniques and single-crystal X-ray analysis. The latter, including Hirshfeld surface analysis, allowed the study of the main non-covalent interactions that stabilize molecular packing and supramolecular arrangements. A preliminarily evaluated by in vitro assays against a panel of six human cancer cell lines and healthy cells using tamoxifen as a reference drug. The results showed that all the compounds demonstrate bioactivity, highlighting the halogenated structures 1-(4-chlorobenzyl)-2-(4-chlorophenyl)-1H-benzo[d]imidazole (26), 1-(4-bromobenzyl)-2-(4-bromophenyl)-1H-benzo[d]imidazole (27) and 1-(4-methoxybenzyl)-2-(4-methoxyphenyl)-1H-bebioavailability nzo[d]imidazole (29) exhibited the highest biological activity, mainly against the cancer lines leukemia (K562), colon cancer (HCT-15), breast cancer (MCF-7) and lung cancer (SKLU-1). A brief ADME analysis evaluated that the obtained compounds have pharmacodynamic and pharmacokinetic parameters to be potentially administered enterally.http://www.sciencedirect.com/science/article/pii/S2211715625001171Green benzimidazole synthesisX-ray structureHirshfeld surfaces studyAnticancer assaysADME analysis |
| spellingShingle | Alcives Avila-Sorrosa Luis Angel Gil-Ruiz María Elena Vargas-Diaz Benjamín Torres-Nogueda David Morales-Morales Green synthesis and in vitro anticancer evaluation of 1,2-disubstituted benzimidazole derivatives Results in Chemistry Green benzimidazole synthesis X-ray structure Hirshfeld surfaces study Anticancer assays ADME analysis |
| title | Green synthesis and in vitro anticancer evaluation of 1,2-disubstituted benzimidazole derivatives |
| title_full | Green synthesis and in vitro anticancer evaluation of 1,2-disubstituted benzimidazole derivatives |
| title_fullStr | Green synthesis and in vitro anticancer evaluation of 1,2-disubstituted benzimidazole derivatives |
| title_full_unstemmed | Green synthesis and in vitro anticancer evaluation of 1,2-disubstituted benzimidazole derivatives |
| title_short | Green synthesis and in vitro anticancer evaluation of 1,2-disubstituted benzimidazole derivatives |
| title_sort | green synthesis and in vitro anticancer evaluation of 1 2 disubstituted benzimidazole derivatives |
| topic | Green benzimidazole synthesis X-ray structure Hirshfeld surfaces study Anticancer assays ADME analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625001171 |
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