Synthesis and biological evaluation of 2-methyl-1H-benzimidazole-5-carbohydrazides derivatives as modifiers of redox homeostasis of Trypanosoma cruzi

Torre, Silvia Melchor-Doncel de la; Vázquez, Citlali; González-Chávez, Zabdi; Yépez‐Mulia, Lilián; Nieto-Meneses, Rocío; Jasso‐Chávez, Ricardo; Saavedra, Emma; Hernández‐Luis, Francisco

doi:10.1016/j.bmcl.2017.06.013

Cited by 13 publications

(6 citation statements)

References 24 publications

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“…However, analysis of 2-ETH effects in the Control group lays oneself to ask: «Why did 2-ETH in contrast to Stress group activate iNOS in the serum and increase expression of the enzyme in the myocardium while didn't affect serum NO 3 -/NO 2 concentration?» Perhaps, 2-ETH could enhance iNOS gene activity [22]. Different benzimidazole derivatives modify cellular redox state by augmentation of GSH synthesis [23], whereas iNOS is redox-sensitive enzyme [24]. Moreover, 2-ETH pretreatment in the Control group could stimulate aggresomes formation [25].…”

Section: Resultsmentioning

confidence: 99%

Benzimidazole Derivative, 2-ETH Prevents Poststressor Disorders of Coronary Vascular Tone and Myocardial Contractility

Лазуко

Беляева

2020

Regional blood circulation and microcirculation

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Introduction. Due to unpredictability of stressors exposure, prevention of stress-induced coronary vascular tone disorders with new classes of drugs with pleiotropic action is quite relevant. At the present time, besides traditionally used vasoactive substances, benzimidazole derivatives with antioxidant and anti-inflammatory activity are considered. The goal of the present study is to test the hypothesis that infusion of the 2-ethyl-thiobenzimidazole hydrobromide (2-ETH) before stress is able to effectively prevent stress-induced disorders of coronary vascular tone and myocardial contractility disorders and clarify mechanisms of such 2-ETH action. Materials and methods. Coronary vascular tone and myocardial contractility were investigated using Langendorff isolated rat heart model. The ВКСа-channel inhibitor, tetraethylammonium (TEA) was added to the Krebs-Henseleit solution to the final concentration of 1 mM. Concentration of the stable products of NO degradation (NO2-/NO3-) was determined spectrophotometrically; activation of lipid peroxidation was assessed in the myocardium using a spectrophotometric method; concentration of iNOS, еNOS, and IL-1β was detected with enzyme-linked immunosorbent assay; concentration of C-reactive protein was estimated with immunoturbidimetric method. Results. 2-ETH pretreatment prevented stress-induced decrease in ВКСа-channels and eNOS activity, limited iNOS activity in coronary vessels and restored myocardial contractility. These 2-ETH' effects together with its ability to prevent alterations of stress-sensitive organs and limit oxidative, nitrozative stress and systemic inflammation argue why 2-ETH should be considered as a useful tool for pathogenetic prevention of stress-induced pathology. Conclusions. 2-ETH should be considered as a useful tool for pathogenetic prevention of stress-induced pathology.

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Section: Resultsmentioning

confidence: 99%

Benzimidazole Derivative, 2-ETH Prevents Poststressor Disorders of Coronary Vascular Tone and Myocardial Contractility

Лазуко

Беляева

2020

Regional blood circulation and microcirculation

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“…[33] In addition, Singh et al reported the conjugation of different substituted benzylidenes to 1,2,4-triazole anchored on a 4-pyridyl moiety which yielded a set of compounds contain a hydrazone structural linker with significant antitubercular potential against MTB H 37 Rv. [34] Compounds containing a hydrazone structural feature have been found to exhibit a range of biological activities, [35][36][37][38][39][40][41][42] and there is a great interest in the biomedicinal potential of the hydrazone derivatives. [43,44] For example, rifampicin (3), nitrofurantoin (4), and nifurtimox (5) (Figure 1) are effective antimicrobial agents all containing a hydrazone bridge.…”

Section: Introductionmentioning

confidence: 99%

Hydrazone‐Tethered 5‐(Pyridin‐4‐yl)‐4H‐1,2,4‐triazole‐3‐thiol Hybrids: Synthesis, Characterisation, in silico ADME Studies, and in vitro Antimycobacterial Evaluation and Cytotoxicity

Oderinlo

Jordaan

Seldon³

et al. 2023

ChemMedChem

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Compounds containing arylpyrrole‐, 1,2,4‐triazole‐ and hydrazone structural frameworks have been widely studied and demonstrated to exhibit a wide range of pharmacological properties. Herein, an exploratory series of new 1,2,4‐triazole derivatives designed by amalgamation of arylpyrrole and 1,2,4‐triazole structural units via a hydrazone linkage is reported. The synthesised compounds were tested in vitro for their potential activity against Mycobacterium tuberculosis (MTB) H37Rv strain. The most promising compound 13 – the derivative without the benzene ring appended to the pyrrole unit displayed acceptable activity (MIC90=3.99 μM) against MTB H37Rv, while other compounds from the series exhibited modest to weak antimycobacterial activity with MIC90 values in the range between 7.0 and >125 μM. Furthermore, in silico results, predicated using the SwissADME web tool, show that the prepared compounds display desirable ADME profile with parameters within acceptable range.

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“…Further attempts to develop improved trypanocidal agents have included studies on benzazoles − and their amidine derivatives, − where enhancement of activity has been achieved through optimization of physicochemical parameters and ADME properties. The introduction of nitrogen atoms into the aromatic rings can change the lipophilicity and polarity of the resulting aza analogues, enabling them to cross the BBB. , Some benzimidazole − and benzothiazole − derivatives have been shown to have potent anti-trypanosomatid activity.…”

Section: Introductionmentioning

confidence: 99%

Bis-6-amidino-benzothiazole Derivative that Cures Experimental Stage 1 African Trypanosomiasis with a Single Dose

Racané,

Ptiček,

Kostrun

et al. 2023

J. Med. Chem.

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We designed and synthesized a series of symmetric bis-6-amidino-benzothiazole derivatives with aliphatic central units and evaluated their efficacy against bloodstream forms of the African trypanosome Trypanosoma brucei. Of these, a dicationic benzothiazole compound (9a) exhibited subnanomolar in vitro potency with remarkable selectivity over mammalian cells (>26,000-fold). Unsubstituted 5-amidine groups and a cyclohexyl spacer were the crucial determinants of trypanocidal activity. In all cases, mice treated with a single dose of 20 mg kg −1 were cured of stage 1 trypanosomiasis. The compound displayed a favorable in vitro ADME profile, with the exception of low membrane permeability. However, we found evidence that uptake by T. brucei is mediated by endocytosis, a process that results in lysosomal sequestration. The compound was also active in low nanomolar concentrations against cultured asexual forms of the malaria parasite Plasmodium falciparum. Therefore, 9a has exquisite cross-species efficacy and represents a lead compound with considerable therapeutic potential.

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Synthesis and biological evaluation of 2-methyl-1H-benzimidazole-5-carbohydrazides derivatives as modifiers of redox homeostasis of Trypanosoma cruzi

Cited by 13 publications

References 24 publications

Benzimidazole Derivative, 2-ETH Prevents Poststressor Disorders of Coronary Vascular Tone and Myocardial Contractility

Benzimidazole Derivative, 2-ETH Prevents Poststressor Disorders of Coronary Vascular Tone and Myocardial Contractility

Hydrazone‐Tethered 5‐(Pyridin‐4‐yl)‐4H‐1,2,4‐triazole‐3‐thiol Hybrids: Synthesis, Characterisation, in silico ADME Studies, and in vitro Antimycobacterial Evaluation and Cytotoxicity

Bis-6-amidino-benzothiazole Derivative that Cures Experimental Stage 1 African Trypanosomiasis with a Single Dose

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