Synthesis, electronic properties, antioxidant and antibacterial activity of some new benzimidazoles.
Two groups of benzimidazole derivatives were synthesized using as precursors 5(6)-substituted 2-mercapto-benzimidazol-thiols and their antioxidant activity was investigated using TBA-MDA test. In the group of 1,3-disubstituted-benzimidazol-2-imines the highest lipid peroxidation inhibition effect 74.04% (IC₅₀=141.89 μg/mL) revealed ethyl [3-(2-ethoxy-2-oxoethyl)-2-imino-5-benzoyl-2,3-dihydro-1H-benzimdazol-1-yl]acetate 12 while in the group of 2-substituted-1,3-thiazolo[3,2-a]benzimidazolones the highest inhibition effect showed 2-(4-fluorobenzylidene)-7-(phenylcarbonyl)[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one 17 90.76% (IC₅₀=53.70 μg/mL). In order to estimate the capability of the studied benzimidazoles to act as radical scavengers the structure of the most active derivative within the both subseries was optimized at B3LYP/6-311++G(∗∗) level and the respective bond dissociation enthalpies were calculated. The appropriate models for the HAT and SET-mechanism of the antioxidant activity were proposed. The antibacterial activity of the compounds was evaluated against two Gram-positive bacteria (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538) and three Gram-negative bacteria (Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027 and Salmonella abony NCTC 6017). 1,3-Diphenylpropyl-5-methyl-1,3-dihydro-2H-benzimidazol-2-imine 14 exhibited significant activity against B. subtilis, S. aureus, S. abony and E. coli (with MIC values of 0.125, 0.016, 0.50 and 0.50mg/mL, respectively). The group of thiazolobenzimidazolones did not reveal antibacterial activity against the tested strains.
Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria. Electronic address: anmav@abv.bg.
Anelia Ts
ATs
Mavrova
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Science, Acad. G Bonchev Str., Build. 9, 1113 Sofia, Bulgaria.
Denitsa
D
Yancheva
Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria.
Neda
N
Anastassova
Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria.
Kamelya
K
Anichina
Faculty of Technology, University of Niš, Bulevar Oslobodjenja 124, 16000 Leskovac, Serbia.
Jelena
J
Zvezdanovic
Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.
Aleksandra
A
Djordjevic
Faculty of Technology, University of Niš, Bulevar Oslobodjenja 124, 16000 Leskovac, Serbia.
Dejan
D
Markovic
Department of Chemistry, Faculty of Medicine, University of Nis, Bulevar Dr Zorana Djindjica 81, 18000 Nis, Serbia.
Andrija
A
Smelcerovic
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D001562:Benzimidazoles
1,3-Thiazolo[3,2-a]benzimidazolones; 2-Imino-benzimidazoles; Antibacterial activity; DFT calculations; Lipid peroxidation inhibition