Synthesis, bioevaluation and docking studies of some 2-phenyl-1H-benzimidazole derivatives as anthelminthic agents against the nematode Teladorsagia circumcincta

Escala, Nerea; Valderas-García, Elora; Bardón, María Álvarez; Agüero, Verónica Castilla Gómez de; Escarcena, Ricardo; López-Pérez, Jose Luis; Rojo-Vázquez, F.A.; Feliciano, Arturo San; Balaña‐Fouce, Rafael; Martínez‐Valladares, María; Olmo, Esther del

doi:10.1016/j.ejmech.2020.112554

Cited by 10 publications

(21 citation statements)

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“…Shaker and co-workers described the reaction of 1-(het)aryl-substituted 2-amino-3-cyano-5-phenylpyrroles 13 with 1,2-DAB 1a in refluxing 4 M HCl, followed by neutralization with NH 4 OH to give 3-(benzimidazol-2-yl)-1-(het)aryl-5-phenyl-1H-pyrrol-2-amines 14 (Scheme 2). 9g Derivatives of 2-amino-3-cyano-5-phenylpyrrole 13 were, in turn, obtained by cyclocondensation of 2-(2-oxo-2phenylethyl)malononitrile (12), readily available from 2bromoacetophenone (10) and malononitrile (11), 37 with various aryl-and hetarylamines in the presence of a few drops of concentrated hydrochloric acid in ethanol. 9g Zhang, Xu, and co-workers showed that pyrazino [1,2c:4,5-c′]diimidazole-1,6-dicarboxamide 17, obtained from pyrazino[1,2-c:4,5-c′]diimidazole-1,6-dicarbonyl dichloride 16 by reaction with Boc-diamine 15 at -78 °C in 92% yield, was a convenient starting compound for the synthesis of 2-[imidazol-4(5)-yl]benzimidazoles 19 with different carboxamide fragments at C5 of the imidazole ring (Scheme 3) and 4,5-bis(benzimidazol-2-yl)imidazoles 21 (Scheme 4) with the same and different benzimidazole fragments by using a facile procedure involving deprotection and cyclization reactions.…”

Section: With (Het)arenecarboxylic Acid Derivativesmentioning

confidence: 99%

“…These structures are valuable bioactive structures and are the basis of many drugs (Figure 2). 2, 3 For example they exhibit anticancer, 9 antiproliferative, 10 antifungal, 11 antihelmintic, 12 antileishmanial, 13 antitubercular, 14 and antimicrobial activity; 15 they act as VEGFR-2, 16 Tpl2 kinase, 17 cryptosporidium parvum IMPDH, 18 and Aurora A/B kinase inhibitors; 19 they are selective inhibitors of carbonic anhydrase isoforms hCA IX and XII, 20 NPY Y5 receptor, 21 and MCH-R1 22 antagonist, and selective A1 adenosine receptor antagonists. 23 In addition, 2-hetarylbenzimidazoles are also used as dyes, 24 fluorescence sensors, 25 corrosion inhibitors, 26 and ligands for the preparation of complexes, 27 including those with practically useful properties: as potential catalysts for the oligomerization of ethylene, 27a for electrocatalytic CO 2 reduction, 27b as reversible fluorescent chemosensor for Fe 3+ and H 2 PO 4 with 'on-off-on' switching in aqueous media, 27c and as an organic light-emitting diode, 27d as an anti-amyloid agent for the therapy of Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

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Recent Developments Towards Synthesis of (Het)arylbenzimidazoles

Мамедов¹,

Zhukova²

2021

Synthesis

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Benzimidazole is an important heterocycle that is widely researched and utilized by the pharmaceutical industry and is one of the five most commonly used five-membered aromatic heterocyclic compounds approved by the US Food and Drug Administration. In view of their wide-ranging bioactivities, systems containing benzimidazole as one of the moieties occupy a special place among other benzimidazole derivatives. Since 2010, many improved synthetic strategies have been developed for the construction of hetaryl- and arylbenzimidazole molecular scaffolds under environmentally benign conditions. This review emphasizes the recent trends and modifications frequently used in the synthesis of derivatives of benzimidazole such as the Phillips–Ladenburg and Weidenhagen reactions, as well as entirely new methods of synthesis, involving oxidative cyclization, cross-coupling, ring distortion strategy, and rearrangements carried out under environmentally benign conditions.1 Introduction2 From 1,2-Diaminobenzenes with Various One-Carbon Unit Suppliers2.1 Phillips–Ladenburg Reaction2.1.1 With (Het)arenecarboxylic Acids2.2.2 With (Het)arenecarboxylic Acid Derivatives2.2 Weidenhagen Reaction2.2.1 With (Het)arenecarbaldehydes or (Het)aryl Methyl Ketones2.2.2 With Primary Alcohols2.2.3 With Primary Alkylamines2.2.4 With 2-Methylazaarenes2.2.5 With Other One-Carbon Fragment Suppliers3 From 2-Haloacetanilides and Amines4 From Amidines5 From Tetrahydroquinazolines6 Mamedov Rearrangement7 Conclusions and Outlook

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Section: With (Het)arenecarboxylic Acid Derivativesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recent Developments Towards Synthesis of (Het)arylbenzimidazoles

Мамедов¹,

Zhukova²

2021

Synthesis

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“…Compounds belonging to three different chemical families, namely 2-aminoalkan-1-ol (AO), alkane-1,2-diamine (AA) and 2-phenylbenzimidazoles (BZ), were synthesised by previously reported procedures [ 16 – 18 ] (structures summarized in Tables 1 , 2 and 3 ). Stock solutions (10 mM) of these compounds were prepared in 100% dimethyl sulphoxide (DMSO; Sigma-Aldrich ® ) while final dilutions were made with distilled water to maintain a maximum concentration of 1% (v/v) DMSO in the well.…”

Section: Methodsmentioning

confidence: 99%

Benzimidazole and aminoalcohol derivatives show in vitro anthelmintic activity against Trichuris muris and Heligmosomoides polygyrus

et al. 2022

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Background Infections by gastrointestinal nematodes cause significant economic losses and disease in both humans and animals worldwide. The discovery of novel anthelmintic drugs is crucial for maintaining control of these parasitic infections. Methods For this purpose, the aim of the present study was to evaluate the potential anthelmintic activity of three series of compounds against the gastrointestinal nematodes Trichuris muris and Heligmosomoides polygyrus in vitro. The compounds tested were derivatives of benzimidazole, lipidic aminoalcohols and diamines. A primary screening was performed to select those compounds with an ability to inhibit T. muris L1 motility by > 90% at a single concentration of 100 µM; then, their respective IC50 values were calculated. Those compounds with IC50 < 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10 µM. Results Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC50 values < 10 µM on T. muris L1 assay, showing IC50 values of 3.30, 8.89 and 4.17 µM, respectively. However, only two of them displayed activity against the adult stage of the parasites: BZ12 killed 81% of adults of T. muris (IC50 of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC50 of 5.3 µM) but only 17% of T. muris. Conclusions BZ6 and BZ12 could be considered as a starting point for the synthesis of further structurally related compounds. Graphical Abstract

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“…The T. circumcincta assay was performed essentially as described previously ( Escala et al, 2020 ). Briefly, eggs were collected from feces from two 3-months old Merino lambs experimentally infected with a field strain of T. circumcincta (susceptible to anthelmintics) maintained in the laboratory ( Martínez-Valladares et al, 2012 ).…”

Section: Methodsmentioning

confidence: 99%

Bio-Guided Fractionation and Molecular Networking Reveal Fatty Acids to Be Principal Anti-Parasitic Compounds in Nordic Seaweeds

Bonde

Bornancin

et al. 2021

Front. Pharmacol.

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Widespread use of antimicrobial drugs has led to high levels of drug-resistance in pathogen populations and a need for novel sources of anti-bacterial and anti-parasitic compounds. Macroalgae (seaweed) are potentially a rich source of bioactive compounds, and several species have traditionally been used as vermifuges. Here, we investigated the anti-parasitic properties of four common cold-water Nordic seaweeds; Palmaria palmata (Rhodophyta), Laminaria digitata, Saccharina latissima and Ascophyllum nodosum (Ochrophyta, Phaeophyceae). Screening of organic extracts against helminths of swine (Ascaris suum) and sheep (Teladorsagia circumcincta) revealed that S. latissima and L. digitata had particularly high biological activity. A combination of molecular networking and bio-guided fractionation led to the isolation of six compounds from extracts of these two species identified in both fermented and non-fermented samples. The six isolated compounds were tentatively identified by using MS-FINDER as five fatty acids and one monoglyceride: Stearidonic acid (1), Eicosapentaenoic acid (2), Alpha-Linolenic acid (3), Docosahexaenoic acid (4), Arachidonic acid (5), and Monoacylglycerol (MG 20:5) (6). Individual compounds showed only modest activity against A. suum, but a clear synergistic effect was apparent when selected compounds were tested in combination. Collectively, our data reveal that fatty acids may have a previously unappreciated role as natural anti-parasitic compounds, which suggests that seaweed products may represent a viable option for control of intestinal helminth infections.

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Synthesis, bioevaluation and docking studies of some 2-phenyl-1H-benzimidazole derivatives as anthelminthic agents against the nematode Teladorsagia circumcincta

Cited by 10 publications

References 32 publications

Recent Developments Towards Synthesis of (Het)arylbenzimidazoles

Recent Developments Towards Synthesis of (Het)arylbenzimidazoles

Benzimidazole and aminoalcohol derivatives show in vitro anthelmintic activity against Trichuris muris and Heligmosomoides polygyrus

Bio-Guided Fractionation and Molecular Networking Reveal Fatty Acids to Be Principal Anti-Parasitic Compounds in Nordic Seaweeds

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