Experimental and Computational Study of the Antioxidative Potential of Novel Nitro and Amino Substituted Benzimidazole/Benzothiazole-2- Carboxamides with Antiproliferative Activity
Autor: | Lucija Hok, Ida Boček, Marijeta Kralj, Kristina Starčević, Marijana Hranjec, Kristina Butković, Irena Sović, Maja Cindrić, Robert Vianello, Marija Mioč, Irena Martin-Kleiner, Petra Roškarić |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
antiproliferative activity Benzimidazole Antioxidant Physiology DPPH medicine.medical_treatment Clinical Biochemistry ros 01 natural sciences Biochemistry Article dft calculations 03 medical and health sciences chemistry.chemical_compound benzimidazoles benzothiazoles carboxamides antioxidative activity ROS DFT calculations medicine Butylated hydroxytoluene Molecular Biology IC50 010405 organic chemistry Chemistry lcsh:RM1-950 Cell Biology Combinatorial chemistry 3. Good health 0104 chemical sciences 030104 developmental biology lcsh:Therapeutics. Pharmacology Benzothiazole Nitro Ferric medicine.drug |
Zdroj: | Antioxidants Antioxidants, Vol 8, Iss 10, p 477 (2019) Volume 8 Issue 10 |
Popis: | We present the synthesis of a range of benzimidazole/benzothiazole-2-carboxamides with a variable number of methoxy and hydroxy groups, substituted with nitro, amino, or amino protonated moieties, which were evaluated for their antiproliferative activity in vitro and the antioxidant capacity. Antiproliferative features were tested on three human cancer cells, while the antioxidative activity was measured using 1,1-diphenyl-picrylhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) assays. Trimethoxy substituted benzimidazole-2-carboxamide 8 showed the most promising antiproliferative activity (IC50 = 0.6&ndash 2.0 µ M), while trihydroxy substituted benzothiazole-2-carboxamide 29 was identified as the most promising antioxidant, being significantly more potent than the reference butylated hydroxytoluene BHT in both assays. Moreover, the latter also displays antioxidative activity in tumor cells. The measured antioxidative capacities were rationalized through density functional theory (DFT) calculations, showing that 29 owes its activity to the formation of two [O&bull ∙∙∙H&ndash O] hydrogen bonds in the formed radical. Systems 8 and 29 were both chosen as lead compounds for further optimization of the benzazole-2-carboxamide scaffold in order to develop more efficient antioxidants and/or systems with the antiproliferative activity. |
Databáze: | OpenAIRE |
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