N-Ferrocenylmethyl, N′-Methyl-2-substituted benzimidazolium iodide salts with In vitro activity against the Leishmania infantum parasite strain L1

Howarth, Joshua; Hanlon, Keith

doi:10.1016/s0960-894x(03)00327-5

Cited by 19 publications

(4 citation statements)

References 5 publications

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“…Nitrogenous heterocycles play a pivotal role in the bioactivity of natural products and pharmaceuticals . Heterocyclic ammonium salts, in particular, exhibit CFTR activation, DNA-intercalating antiproliferative activity as well as antimalarial and antileishmanial activities, to name a few. Saturated and partially saturated pyrido[1,2- a ]pyrimidines belong to the broad class of bioactive bicyclic 6–6 fused systems bearing one nitrogen at the ring junction and another nitrogen elsewhere in the ring …”

mentioning

confidence: 99%

Regio- and Diastereoselective Synthesis of Dihydropyridopyrimidines via Cascade Reactions of 2-Aminopyridines with Morita–Baylis–Hillman Bromides of Nitroalkenes

Satham

Namboothiri

2017

J. Org. Chem.

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The Morita-Baylis-Hillman (MBH) bromides of nitroalkenes have been employed as bielectrophiles for the first time. The 1,3-bielectrophilic reactivity of the MBH bromides has been demonstrated in the synthesis of 3,4-dihydro-2H-pyrido[1,2-a]pyrimidines. The reaction of MBH bromides with 2-aminopyridines takes place in the absence of any reagent in a cascade S2'-6-endo-trig fashion and is completely regioselective and highly stereoselective. The products, in their hydrobromide salt form, could be conveniently isolated and purified by crystallization. The high stereoselectivity has been rationalized in terms of the greater stability of the transition state in which the Ar and NO groups are anti to each other.

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mentioning

confidence: 99%

Regio- and Diastereoselective Synthesis of Dihydropyridopyrimidines via Cascade Reactions of 2-Aminopyridines with Morita–Baylis–Hillman Bromides of Nitroalkenes

Satham

Namboothiri

2017

J. Org. Chem.

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“…4). Interestingly, these were all N -ferrocenylmethyl, N '-methyl-2-substituted benzimidazoles and benzimidazolium iodide salts belonging to a chemical series that included 26 compounds [47].…”

Section: Chemotype Analysismentioning

confidence: 99%

“…Howarth and Hanlon [47] reported the synthesis of 26 425 benzimidazolium derivatives that were evaluated against L. 426 infantum; however, they did not indicate whether the assays 427 were performed on promastigotes and no technical details 428 were provided. It is therefore difficult to compare their work 429 with our results directly, although our findings showed that 430 G2 significantly affected L. infantum promastigotes and 431 amastigotes, with IC 50 values below 25 µM.…”

Section: Activity Against Promastigotes and Amastigotesmentioning

confidence: 99%

Systematic search for benzimidazole compounds and derivatives with antileishmanial effects

et al. 2018

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Leishmaniasis is a neglected tropical disease that currently affects 12 million people, and over 1 billion people are at risk of infection. Current chemotherapeutic approaches used to treat this disease are unsatisfactory, and the limitations of these drugs highlight the necessity to develop treatments with improved efficacy and safety. To inform the rational design and development of more efficient therapies, the present study reports a chemoinformatic approach using the ChEMBL database to retrieve benzimidazole as a target scaffold. Our analysis revealed that a limited number of studies had investigated the antileishmanial effects of benzimidazoles. Among this limited number, L. major was the species most commonly used to evaluate the antileishmanial effects of these compounds, whereas L. amazonensis and L. braziliensis were used least often in the reported studies. The antileishmanial activities of benzimidazole derivatives were notably variable, a fact that may depend on the substitution pattern of the scaffold. In addition, we investigated the effects of a benzimidazole derivative on promastigotes and amastigotes of L. infantum and L. amazonensis using a novel fluorometric method. Significant antileishmanial effects were observed on both species, with L. amazonensis being the most sensitive. To the best of our knowledge, this chemoinformatic analysis represents the first attempt to determine the relevance of benzimidazole scaffolds for antileishmanial drug discovery using the ChEMBL database. The present findings will provide relevant information for future structure-activity relationship studies and for the investigation of benzimidazole-derived drugs as potential treatments for leishmaniasis.

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“…Particularly, in organometallic chemistry, chemistry, benzimidazolium salts have emerged as an influential class of ligands due to strong σ-donor and weak π-accepting ability. Besides multiple synthetic and catalytic applications, benzimidazolium salts are also proven as effective antibacterial 1 [15], anticancer 2 [16], antimalarial, and anti-leishmanial agents 3 [17,18] (Figure 1). Diabetes mellitus is a prevailing disorder, arisen due to a high level of blood glucose.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Amide-Functionalized Benzimidazolium Salts as Potent α-Glucosidase Inhibitors

et al. 2021

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α-Glucosidase inhibitors (AGIs) are used as medicines for the treatment of diabetes mellitus. The α-Glucosidase enzyme is present in the small intestine and is responsible for the breakdown of carbohydrates into sugars. The process results in an increase in blood sugar levels. AGIs slow down the digestion of carbohydrates that is helpful in controlling the sugar levels in the blood after meals. Among heterocyclic compounds, benzimidazole moiety is recognized as a potent bioactive scaffold for its wide range of biologically active derivatives. The aim of this study is to explore the α-glucosidase inhibition ability of benzimidazolium salts. In this study, two novel series of benzimidazolium salts, i.e., 1-benzyl-3-{2-(substituted) amino-2-oxoethyl}-1H-benzo[d]imidazol-3-ium bromide 9a–m and 1-benzyl-3-{2-substituted) amino-2-oxoethyl}-2-methyl-1H-benzo[d] imidazol-3-ium bromide 10a–m were screened for their in vitro α-glucosidase inhibitory potential. These compounds were synthesized through a multistep procedure and were characterized by 1H-NMR, 13C-NMR, and EI-MS techniques. Compound 10d was identified as the potent α-glucosidase inhibitor among the series with an IC50 value of 14 ± 0.013 μM, which is 4-fold higher than the standard drug, acarbose. In addition, compounds 10a, 10e, 10h, 10g, 10k, 10l, and 10m also exhibited pronounced potential for α-glucosidase inhibition with IC50 value ranging from 15 ± 0.037 to 32.27 ± 0.050 µM when compared with the reference drug acarbose (IC50 = 58.8 ± 0.12 μM). A molecular docking study was performed to rationalize the binding interactions of potent inhibitors with the active site of the α-glucosidase enzyme.

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N-Ferrocenylmethyl, N′-Methyl-2-substituted benzimidazolium iodide salts with In vitro activity against the Leishmania infantum parasite strain L1

Cited by 19 publications

References 5 publications

Regio- and Diastereoselective Synthesis of Dihydropyridopyrimidines via Cascade Reactions of 2-Aminopyridines with Morita–Baylis–Hillman Bromides of Nitroalkenes

Regio- and Diastereoselective Synthesis of Dihydropyridopyrimidines via Cascade Reactions of 2-Aminopyridines with Morita–Baylis–Hillman Bromides of Nitroalkenes

Systematic search for benzimidazole compounds and derivatives with antileishmanial effects

Discovery of Amide-Functionalized Benzimidazolium Salts as Potent α-Glucosidase Inhibitors

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