Clinically significant antibiotic resistance is one of the greatest challenges of the twenty‐first century. However, new antibacterial agents are currently being developed at a much slower pace than our growing need for such drugs. Given their diverse biological activities and clinical applications, many bioactive heterocyclic compounds containing a benzimidazole nucleus have been the focus of interest for many researchers. The benzimidazole nucleus is a structural isostere of naturally occurring nucleotides. This advantage allows benzimidazoles to readily interact with the various biopolymers found in living systems. In view of this situation, much attention has been given to the exploration of benzimidazole‐based antibacterial agents, leading to the discovery of many new chemical entities with intriguing profiles. In this minireview we summarize novel benzimidazole derivatives active against various bacterial strains. In particular, we outline the relationship between the structures of variously modified benzimidazoles and their antibacterial activity. 相似文献
Probing SAR : The 1‐(biphenyl‐4‐ylmethyl)‐1H‐benzo[d]imidazole moiety is known to be an essential structural component of telmisartan for PPARγ activation. This study focused on the substituents at position 2 of the benzimidazole in an attempt to optimize PPARγ activation. In particular, the elongation of the alkyl chain and the introduction of an aromatic ring system were studied (shown).
Although manure is an important source of minerals and organic compounds it represents a certain risk of spreading the veterinary drugs in the farmland and their permeation to human food. We tested the uptake of the anthelmintic drug fenbendazole (FBZ) by soybean, a common crop plant, from the soil and its biotransformation and accumulation in different soybean organs, including beans. Soybeans were cultivated in vitro or grown in a greenhouse in pots. FBZ was extensively metabolized in roots of in vitro seedlings, where sixteen metabolites were identified, and less in leaves, where only two metabolites were found. The soybeans in greenhouse absorbed FBZ by roots and translocated it to the leaves, pods, and beans. In roots, leaves, and pods two metabolites were identified. In beans, FBZ and one metabolite was found. FBZ exposure did not affect the plant fitness or yield, but reduced activities of some antioxidant enzymes and isoflavonoids content in the beans. In conclusion, manure or biosolids containing FBZ and its metabolites represent a significant risk of these pharmaceuticals entering food consumed by humans or animal feed. In addition, the presence of these drugs in plants can affect plant metabolism, including the production of isoflavonoids. 相似文献
A colloidal gold immunochromatographic assay based on a generic monoclonal antibody is developed for the simultaneous detection of benzimidazoles and metabolite residues in milk samples. The monoclonal antibody is prepared using 2‐(methoxycarbonylamino)‐3H‐benzimidazole‐5‐carboxylic acid as the hapten, and it can recognize 11 types of benzimidazoles simultaneously. The immunochromatographic strip is assembled and labeled using gold nanoparticles. This strip can detect 11 benzimidazoles including albendazole, albendazole s‐oxide, albendazole sulfone, fenbendazole, fenbendazole sulfone, flubendazole, mebendazole, parbendazole, oxfendazole, oxibendazole, and carbendazim within 15 min in milk samples. Results are obtained visually with the naked eye, and the cutoff values and the visual limit of detection values for these benzimidazoles are 25, 6.25, 12.5, 12.5, 50, 25, 50, 50, 50, 6.25, and 25 ng mL?1, and 6.25, 3.125, 3.125, 1.56, 12.5, 6.25, 12.5, 12.5, 6.25, 0.78, and 12.5 ng mL?1, respectively. Results are also obtained using a hand‐held strip scan reader, with calculated limit of detection values for these benzimidazoles of 0.83, 0.77, 1.83, 0.98, 7.67, 3.50, 3.96, 5.71, 0.92, 0.59, and 1.69 ng mL?1, respectively. In short, the developed paper sensor is a useful tool for rapid and simple screening of residues of benzimidazoles in milk samples. 相似文献
Devising ways to up‐ or down‐regulate heme oxygenase activity is attracting much interest as a strategy for the treatment of a variety of disorders. With a view of obtaining compounds that exhibit high potency and selectivity as inhibitors of the heme oxygenase‐2 (HO‐2) isozyme (constitutive) relative to the heme oxygenase‐1 (HO‐1) isozyme (inducible), several 1,2‐disubstituted 1H‐benzimidazoles were designed and synthesized. Specifically, analogues were synthesized in which the C2 substituent was the following: (1H‐imidazol‐1‐yl)methyl, (N‐morpholinyl)methyl, cyclopentylmethyl, cyclohexylmethyl, or (norborn‐2‐yl)methyl. Compounds with the cyclic system in the C2 substituent being a carbocyclic ring, especially cyclohexyl or norborn‐2‐yl, and the N1 substituent being a ring‐substituted benzyl group, especially 4‐chlorobenzyl or 4‐bromobenzyl, best exhibited the target criteria of high potency and selectivity toward inhibition of HO‐2. The new candidates should be useful pharmacological tools and may have therapeutic applications. 相似文献
The pyrimido[1,2-a]benzimidazole derivatives compounds 1–8 were synthesized through cyclocondensation of 2-aminobenzimidazole with the appropriate benzsubstituted benzoylacetone by fusion at 150–170°C for 5 h. Quaternary salts compounds 9–22 were obtained by quaternization of compounds 1–8 with dimethyl or diethyl sulfate and subsequent isolation as the relatively insoluble perchlorate salts. Assignment and confirmation of the structures of the newly synthesized compounds were based upon elemental microanalyses and other spectral evidence. 相似文献
A series of compounds structurally related to astemizole were designed and synthesized with the goal of determining their anti‐Plasmodium activity. Several modifications of the astemizole structure, namely the removal of the 4‐fluorobenzyl and/or 4‐methoxyphenethyl moieties, substitution of the benzene ring of the benzimidazole scaffold, replacement of the fluorine atom in the 4‐fluorobenzyl group, and variation of the 4‐aminopiperidine moiety, were explored. In vitro evaluation of the anti‐Plasmodium activity of these compounds using the ItG strain showed that astemizole and some of its structurally similar derivatives have IC50 values in the nanomolar range and exhibit toxicity towards the parasite over Chinese ovarian hamster (CHO) cells with a selectivity as high as 200. The presence of a secondary cyclic amine at position 2 and substitution with chlorine at positions 4 and 5 in the benzimidazole moiety are two modifications that resulted in potent and selective antimalarials based on astemizole. 相似文献