title: One-pot microwave assisted synthesis under green chemistry conditions, antioxidant screening, and cytotoxicity assessments of benzimidazole Schiff bases and pyrimido[1,2-a]benzimidazol-3(4H)-ones.
abstract: The synthesis of a number of benzimidazole Schiff bases 3 and 3-oxo-pyrimido[1,2-a]benzimidazoles 4 in excellent yields by a one-step sequence from the reaction of 2-aminobenzimidazole under green chemistry conditions is described. Structural assignments of the new compounds as well as complete assignment of (1)H and (13)C NMR signals have been unambiguously achieved based on the analysis of their (1)H and (13)C NMR (1D and 2D), IR, MS and elemental analysis data. To the synthesized Schiff bases the E-configuration was assigned on the basis of comparison of experimental and calculated (DFT) (13)C NMR chemical shifts. Compounds 3 and 4 were evaluated as inhibitors of lipoxygenase (LOX) and of lipid peroxidation (LPO). All the tested derivatives showed inhibition of lipid peroxidation, whereas most of them were found to have higher activation than the reference compound trolox; The Schiff bases 3e, 3h, and 3i, and the pyrimidobenzimidazoles 4a, 4e and 4f were found to be the most potent. The most potent LOX inhibitor within the subset of Schiff bases was found compound 3i, followed by 3f, whereas compounds 4a and 4g were found the most potent of the 3-oxo-pyrimido[1,2-a]benzimidazole group. Moreover, some cytotoxicity assessments were undertaken, whereupon it was found that Schiff base 3i and pyrimidobenzimidazoles 4e and 4f did not exhibit cytotoxicity at similar concentrations resembling thus the inhibitory activity of lipid peroxidation. The most cytotoxic Schiff base and pyrimidobenzimidazole were found to be 3d and 4c, respectively.
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54124, Macedonia, Greece.
authors.forename: Constantinos G
authors.initials: CG
authors.lastname: Neochoritis
authors.forename: Tryfon
authors.initials: T
authors.lastname: Zarganes-Tzitzikas
authors.forename: Constantinos A
authors.initials: CA
authors.lastname: Tsoleridis
authors.forename: Julia
authors.initials: J
authors.lastname: Stephanidou-Stephanatou
authors.forename: Christos A
authors.initials: CA
authors.lastname: Kontogiorgis
authors.forename: Dimitra J
authors.initials: DJ
authors.lastname: Hadjipavlou-Litina
authors.forename: Theodora
authors.initials: T
authors.lastname: Choli-Papadopoulou
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D055772:Green Chemistry Technology / Q000379:methods*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008084:Lipoxygenase / Q000378:metabolism; D008872:Microwaves; D010100:Oxygen / Q000378:metabolism; D012545:Schiff Bases / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000975:Antioxidants; D001562:Benzimidazoles; D005227:Fatty Acids; D012545:Schiff Bases; C031000:benzimidazole; D008084:Lipoxygenase; D010100:Oxygen