Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationship
A new method for the synthesis of 1,3-disubstituted benzimidazole derivatives was developed using aza-Michael addition. The target compounds were synthesized in good yields and purity and tested on isolated hepatocytes for their toxicity and antioxidant activity. The antioxidant properties of the su...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535216302362 |
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| author | Neda O. Anastassova Anelia Ts. Mavrova Denitsa Y. Yancheva Magdalena S. Kondeva-Burdina Virginia I. Tzankova Simeon S. Stoyanov Boris L. Shivachev Rositsa P. Nikolova |
| author_facet | Neda O. Anastassova Anelia Ts. Mavrova Denitsa Y. Yancheva Magdalena S. Kondeva-Burdina Virginia I. Tzankova Simeon S. Stoyanov Boris L. Shivachev Rositsa P. Nikolova |
| author_sort | Neda O. Anastassova |
| collection | DOAJ |
| description | A new method for the synthesis of 1,3-disubstituted benzimidazole derivatives was developed using aza-Michael addition. The target compounds were synthesized in good yields and purity and tested on isolated hepatocytes for their toxicity and antioxidant activity. The antioxidant properties of the substances with lowest toxicity were evaluated using oxidative stress induced by tert-butyl hydroperoxide (tert-BOOH). Some of them as methyl 3-[3-(3-methoxy-3-oxopropyl)-5-benzoyl-2-thioxo-2,3-dihydro-1H-benzimidazol-1-yl]propanoate 10 and 1,3-bis[3-(hydrazinooxy)-3-oxopropyl]-5-benzoyl-1,3-dihydro-2H-benzimidazole-2-thione 15 exhibited statistically significant cytoprotective and antioxidant effects which were similar to those of quercetin. In order to estimate the influence of the structure on the biological properties, structural characterization of the studied compounds was performed by X-ray diffraction analysis and DFT methods. On the basis of the calculated reaction enthalpies of hydrogen atom abstraction (HAT mechanism) and single-electron transfer (SET mechanism) the mechanisms of the antioxidant action of the tested compounds were studied. Subsequently it was established that the HAT mechanism governs the radical scavenging of 10 and 15 in the lipid phase, while the SET mechanism is preferred in water medium for 10 and competitive to HAT for 15. |
| first_indexed | 2024-12-11T07:41:09Z |
| format | Article |
| id | doaj.art-b79a079cee824126ad5c93fcbcb3f653 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-12-11T07:41:09Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-b79a079cee824126ad5c93fcbcb3f6532022-12-22T01:15:34ZengElsevierArabian Journal of Chemistry1878-53522018-03-0111335336910.1016/j.arabjc.2016.12.003Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationshipNeda O. Anastassova0Anelia Ts. Mavrova1Denitsa Y. Yancheva2Magdalena S. Kondeva-Burdina3Virginia I. Tzankova4Simeon S. Stoyanov5Boris L. Shivachev6Rositsa P. Nikolova7University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaUniversity of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaInstitute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Build. 9, 1113 Sofia, BulgariaDrug Metabolism and Drug Toxicity Laboratory, Pharmacology, Pharmacotherapy and Toxicology Department, Faculty of Pharmacy, Medical University-Sofia, BulgariaDrug Metabolism and Drug Toxicity Laboratory, Pharmacology, Pharmacotherapy and Toxicology Department, Faculty of Pharmacy, Medical University-Sofia, BulgariaInstitute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Build. 9, 1113 Sofia, BulgariaAcad. Ivan Kostov Institute of Mineralogy and Crystallography, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Build. 107, 1113 Sofia, BulgariaAcad. Ivan Kostov Institute of Mineralogy and Crystallography, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Build. 107, 1113 Sofia, BulgariaA new method for the synthesis of 1,3-disubstituted benzimidazole derivatives was developed using aza-Michael addition. The target compounds were synthesized in good yields and purity and tested on isolated hepatocytes for their toxicity and antioxidant activity. The antioxidant properties of the substances with lowest toxicity were evaluated using oxidative stress induced by tert-butyl hydroperoxide (tert-BOOH). Some of them as methyl 3-[3-(3-methoxy-3-oxopropyl)-5-benzoyl-2-thioxo-2,3-dihydro-1H-benzimidazol-1-yl]propanoate 10 and 1,3-bis[3-(hydrazinooxy)-3-oxopropyl]-5-benzoyl-1,3-dihydro-2H-benzimidazole-2-thione 15 exhibited statistically significant cytoprotective and antioxidant effects which were similar to those of quercetin. In order to estimate the influence of the structure on the biological properties, structural characterization of the studied compounds was performed by X-ray diffraction analysis and DFT methods. On the basis of the calculated reaction enthalpies of hydrogen atom abstraction (HAT mechanism) and single-electron transfer (SET mechanism) the mechanisms of the antioxidant action of the tested compounds were studied. Subsequently it was established that the HAT mechanism governs the radical scavenging of 10 and 15 in the lipid phase, while the SET mechanism is preferred in water medium for 10 and competitive to HAT for 15.http://www.sciencedirect.com/science/article/pii/S18785352163023621,3-Disubstituted benzimidazole-2-thionesMichael additionHepatotoxicityOxidative stressRadical scavengingDFT calculations |
| spellingShingle | Neda O. Anastassova Anelia Ts. Mavrova Denitsa Y. Yancheva Magdalena S. Kondeva-Burdina Virginia I. Tzankova Simeon S. Stoyanov Boris L. Shivachev Rositsa P. Nikolova Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationship Arabian Journal of Chemistry 1,3-Disubstituted benzimidazole-2-thiones Michael addition Hepatotoxicity Oxidative stress Radical scavenging DFT calculations |
| title | Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationship |
| title_full | Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationship |
| title_fullStr | Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationship |
| title_full_unstemmed | Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationship |
| title_short | Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationship |
| title_sort | hepatotoxicity and antioxidant activity of some new n n disubstituted benzimidazole 2 thiones radical scavenging mechanism and structure activity relationship |
| topic | 1,3-Disubstituted benzimidazole-2-thiones Michael addition Hepatotoxicity Oxidative stress Radical scavenging DFT calculations |
| url | http://www.sciencedirect.com/science/article/pii/S1878535216302362 |
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