In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against cutaneous, mucocutaneous and visceral Leishmania species

Nieto-Meneses, Rocío; Castillo, Rafael; Hernández‐Campos, Alicia; Maldonado-Rangel, Armando; Matius-Ruiz, Jeferson B.; Trejo-Soto, Pedro Josué; Nogueda‐Torres, Benjamín; Dea-Ayuela, María Auxiliadora; Bolás‐Fernández, F.; Méndez-Cuesta, Carlos A.; Yépez‐Mulia, Lilián

doi:10.1016/j.exppara.2017.11.009

Cited by 18 publications

(14 citation statements)

References 47 publications

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“…However, this effect was greater in benzyl compounds (A) than in naphthalene compound (B), which may be due to its smaller structure and thus greater penetration into the parasite. Also, in various studies, the role and effect of benzyl-containing compounds on various microorganisms and parasites have been confirmed [ [26] , [27] , [28] , [29] ], as in our study, the benzyl derivative showed an ability of over 80% in eliminating Toxoplasma tachyzoites. The main proposed mechanism of action by benzyl compounds may be impaired macromolecular biosynthesis and cell death.…”

Section: Discussionsupporting

confidence: 85%

Synthesis and anti- Toxoplasma activity of indole-triazole compounds on tachyzoites of RH strain

Bahreini

Iraji

Monfared

et al. 2022

Annals of Medicine &Amp; Surgery

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Background Conventional treatment for toxoplasmosis have severe side effects and the inability to completely eradicate the disease. Therefore, the acquisition of new anti- Toxoplasma drugs has always been of interest among researchers. In the present study, we prepare a new indole-triazole derivatives and evaluated their potential anti-parasitic activity against tachyzoites of Toxoplasma RH strain. Materials and methods In this study, after synthesis of the two new compounds of indole-triazole, the effect of their different concentrations (2–1024 μg/ml) were determined on Toxoplasma tachyzoites using flow cytometry. Furthermore, tachyzoites were exposed to different concentrations of compounds (4, 16, 64, 265, 1024 μg/ml) for 1.5 h and their infectivity were evaluated in BALB/c mice. Results The flow cytometry results indicated the benzyl derivative of indole-triazole in various concentrations had a lethal effect on tachyzoites between 11.93% and 89.66%, while the naphthalene derivative had a lethality of 26.63%–66.82%. The infectivity analysis showed that the survival time of mice at concentrations of 1024 μg/ml and 512 μg/ml of benzyl derivatives was significantly increased ( P = 0.008 and P = 0.016, respectively), compared to that in the negative control group. Furthermore, survival time of mice was statistically significant at the concentration of 1024 μg/ml for naphthyl derivative ( P = 0.012). Conclusion Findings of the current study suggested indole triazole compounds, based on their structure and enzymes targeting, have a considerable effect on tachyzoites of T. gondii RH strain and can be considered as a new anti- Toxoplasma agent.

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Section: Discussionsupporting

confidence: 85%

Synthesis and anti- Toxoplasma activity of indole-triazole compounds on tachyzoites of RH strain

Bahreini

Iraji

Monfared

et al. 2022

Annals of Medicine &Amp; Surgery

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“…In addition, authors evaluated the inhibitory activity of compound 8 against recombinant LmARG using the Quantichom Arginase Activity Assay kit, and determined an I 50 of 35.9 µM. Nevertheless, the difference between I 50 and IC 50 values, many times lower in the parasite, suggested that there are more targets for these molecules in the parasite apart from arginase [34]. To the contrary, this relationship (I 50 and IC 50 values) in compounds 1 and 2 suggest that arginase could be the principal target in the parasite (Figure 1 and Table 2).…”

Section: Discussionmentioning

confidence: 99%

Benzimidazole Derivatives as New and Selective Inhibitors of Arginase from Leishmania mexicana with Biological Activity against Promastigotes and Amastigotes

Betancourt-Conde

Avitia-Domínguez

Hernández‐Campos

et al. 2021

IJMS

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Leishmaniasis is a disease caused by parasites of the Leishmania genus that affects 98 countries worldwide, 2 million of new cases occur each year and more than 350 million people are at risk. The use of the actual treatments is limited due to toxicity concerns and the apparition of resistance strains. Therefore, there is an urgent necessity to find new drugs for the treatment of this disease. In this context, enzymes from the polyamine biosynthesis pathway, such as arginase, have been considered a good target. In the present work, a chemical library of benzimidazole derivatives was studied performing computational, enzyme kinetics, biological activity, and cytotoxic effect characterization, as well as in silico ADME-Tox predictions, to find new inhibitors for arginase from Leishmania mexicana (LmARG). The results show that the two most potent inhibitors (compounds 1 and 2) have an I50 values of 52 μM and 82 μM, respectively. Moreover, assays with human arginase 1 (HsARG) show that both compounds are selective for LmARG. According to molecular dynamics simulation studies these inhibitors interact with important residues for enzyme catalysis. Biological activity assays demonstrate that both compounds have activity against promastigote and amastigote, and low cytotoxic effect in murine macrophages. Finally, in silico prediction of their ADME-Tox properties suggest that these inhibitors support the characteristics to be considered drug candidates. Altogether, the results reported in our study suggest that the benzimidazole derivatives are an excellent starting point for design new drugs against leishmanisis.

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“…Tonelli and co-workers ( Tonelli et al, 2018 ) reported in vitro antileishmanial activity of derivatives 345–346 with IC 50 values of 3.70 and 0.19 µM, respectively against L. tropica , and 4.76 and 0.64 µM, respectively against L. infantum . In another research, a total of 28 N -benzyl-1 H -benzimidazol-2-amine derivatives, where compounds 347–348 showed significant ( p < 0.05) antileishmanial activity against the amastigote of L. mexicana and L. braziliensis with IC 50 values of 2.62 and 3.21 µM, respectively, and their activity was 5.8 and 4.8 times better than standard miltefosine (IC 50 = 15.34 µM) ( Nieto-Meneses et al, 2018 ). Upon evaluation of in vitro antileishmanial activity against intracellular amastigotes of L. infantum , compound 349 displayed promising result with IC 50 value of 6.8 μM.…”

Section: Biological Activitiesmentioning

confidence: 99%

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

et al. 2021

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Nowadays, nitrogenous heterocyclic molecules have attracted a great deal of interest among medicinal chemists. Among these potential heterocyclic drugs, benzimidazole scaffolds are considerably prevalent. Due to their isostructural pharmacophore of naturally occurring active biomolecules, benzimidazole derivatives have significant importance as chemotherapeutic agents in diverse clinical conditions. Researchers have synthesized plenty of benzimidazole derivatives in the last decades, amidst a large share of these compounds exerted excellent bioactivity against many ailments with outstanding bioavailability, safety, and stability profiles. In this comprehensive review, we have summarized the bioactivity of the benzimidazole derivatives reported in recent literature (2012–2021) with their available structure-activity relationship. Compounds bearing benzimidazole nucleus possess broad-spectrum pharmacological properties ranging from common antibacterial effects to the world’s most virulent diseases. Several promising therapeutic candidates are undergoing human trials, and some of these are going to be approved for clinical use. However, notable challenges, such as drug resistance, costly and tedious synthetic methods, little structural information of receptors, lack of advanced software, and so on, are still viable to be overcome for further research.

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In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against cutaneous, mucocutaneous and visceral Leishmania species

Cited by 18 publications

References 47 publications

Synthesis and anti- Toxoplasma activity of indole-triazole compounds on tachyzoites of RH strain

Synthesis and anti- Toxoplasma activity of indole-triazole compounds on tachyzoites of RH strain

Benzimidazole Derivatives as New and Selective Inhibitors of Arginase from Leishmania mexicana with Biological Activity against Promastigotes and Amastigotes

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

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