Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationship

Arabian Journal of Chemistry

Boris L. Shivachev¹  Rositsa P. Nikolova¹  Virginia I. Tzankova²  Magdalena S. Kondeva-Burdina²  Simeon S. Stoyanov³  Denitsa Y. Yancheva³  Neda O. Anastassova⁴  Anelia Ts. Mavrova⁴ 

[1]Acad. Ivan Kostov Institute of Mineralogy and Crystallography, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Build. 107, 1113 Sofia, Bulgaria

[2]Drug Metabolism and Drug Toxicity Laboratory, Pharmacology, Pharmacotherapy and Toxicology Department, Faculty of Pharmacy, Medical University-Sofia, Bulgaria

[3]Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Build. 9, 1113 Sofia, Bulgaria

[4]University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria

关键词: 1,3-Disubstituted benzimidazole-2-thiones;    Michael addition;    Hepatotoxicity;    Oxidative stress;    Radical scavenging;    DFT calculations;   

DOI  :  10.1016/j.arabjc.2016.12.003

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown