New 1<i>H</i>-benzimidazole-2-yl hydrazones with combined antiparasitic and antioxidant activity

Argirova, Maria; Georgieva, M. K.; Hristova-Avakumova, Nadya; Vuchev, Dimitar; Popova-Daskalova, Galya; Anichina, Kameliya; Yancheva, Denitsa

doi:10.1039/d1ra07419a

Cited by 23 publications

(21 citation statements)

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“…As the radical scavenging ability of the antioxidants is related to the stability of the formed radicals, the delocalization of the unpaired electron over the conjugated system is an important factor to be examined. , In order to estimate the stability of radicals of compounds 3a and 3e , the natural bond orbital (NBO) spin density distribution was calculated and compared for the radicals of 3a and 3e expected to form in the fHAT process. The respective spin density distributions are visualized in Figures and .…”

Section: Resultsmentioning

confidence: 99%

“…The comparison between TS3aH25( • OCH 3 ) and TS3eH25( • OCH 3 ) shows that the distances N•••H and H•••O have small differences in the atom distances (1.143 and 1.120 and 1.295 and 1.350 Å, respectively), whereas the different attacking radicals at the same compound (for example, TS3aH25( • OCH 3 ) and As the radical scavenging ability of the antioxidants is related to the stability of the formed radicals, the delocalization of the unpaired electron over the conjugated system is an important factor to be examined. 40,41 In order to estimate the stability of radicals of compounds 3a and 3e, the natural bond orbital (NBO) spin density distribution was calculated and compared for the radicals of 3a and 3e expected to form in the fHAT process. The respective spin density distributions are visualized in Figures 4 and 5.…”

Section: The Journal Of Physical Chemistry Bmentioning

confidence: 99%

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Radical Scavenging Mechanisms of 1-Arylhydrazone Benzimidazole Hybrids with Neuroprotective Activity

et al. 2023

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Benzimidazole-arylhydrazone hybrids showed promising potential as multifunctional drugs for the treatment of neurodegenerative disorders. The neuroprotection studies conducted using an in vitro model of H2O2-induced oxidative stress on the SH-SY5Y cell line revealed a remarkable activity of the compound possessing a vanilloid structural fragment. The cell viability was preserved up to 84% and this effect was significantly higher than the one exerted by the reference compounds melatonin and rasagiline. Another compound with a catecholic moiety demonstrated the second-best neuroprotective activity. Computational studies were further conducted to characterize in depth the antioxidant properties of both compounds. The possible radical scavenging mechanisms were estimated as well as the most reactive sites through which the compounds may deactivate a variety of free radicals. Both of the compounds are able to deactivate not only the highly reactive hydroxyl radicals but also alkoxyl and hydroperoxyl radicals, following hydrogen atom transfer or radical adduct formation mechanism. In nonpolar medium, 3e is predicted to react slightly faster than 3a with alkoxyl radicals and around two orders of magnitude faster than 3a with hydroperoxyl radicals. The most reactive sites for formal hydrogen atom transfer in 3a are the meta-hydroxy group in the phenyl ring in water and the amide N–H group in benzene; in 3e, the amide N–H group is more reactive in both solvents. The radical adduct formation can occur at several positions in 3a and 3e, the most active being C4, C6, and C14. The stability of the formed radicals was estimated by NBO calculations. The NBO calculations indicated that the spin density in the radicals formed by the abstraction of a hydrogen atom from the amide groups of both compounds is delocalized over the phenyl ring and the hydrazone chain. The obtained theoretical data for the better radical scavenging ability of the vanilloid hybrid corroborate its experimentally established better neuroprotective activity.

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Section: Resultsmentioning

confidence: 99%

Section: The Journal Of Physical Chemistry Bmentioning

confidence: 99%

Radical Scavenging Mechanisms of 1-Arylhydrazone Benzimidazole Hybrids with Neuroprotective Activity

et al. 2023

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“…The filtrate was acidified with hydrochloric acid to pH = 1, and the resulting precipitate of the sulfonic acid was filtered off and washed with water. The 1 H-benzimidazol-2-yl-sulfonic acid 3 was converted to hydrazine 4 by refluxing it for 3 h in excess of 99% hydrazine hydrate according to the described protocol [ 37 ]. Finally, the target compound 5 was synthesized through condensation between 1 H-benzimidazole-2-yl-hydrazine 4 and 3,4,5-trimethoxybenzaldehyde in a molar ratio 1:1 using 99% ethanol as a solvent.…”

Section: Resultsmentioning

confidence: 99%

Novel Fluorescent Benzimidazole-Hydrazone-Loaded Micellar Carriers for Controlled Release: Impact on Cell Toxicity, Nuclear and Microtubule Alterations in Breast Cancer Cells

et al. 2023

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Fluorescent micellar carriers with controlled release of a novel anticancer drug were developed to enable intracellular imaging and cancer treatment simultaneously. The nanosized fluorescent micellar systems were embedded with a novel anticancer drug via the self-assembling behavior of well-defined block copolymers based on amphiphilic poly(acrylic acid)-block-poly(n-butyl acrylate) (PAA-b-PnBA) copolymer obtained by Atom Transfer Radical Polymerization (ATRP) and hydrophobic anticancer benzimidazole-hydrazone drug (BzH). Through this method, well-defined nanosized fluorescent micelles were obtained consisting of a hydrophilic PAA shell and a hydrophobic PnBA core embedded with the BzH drug due to the hydrophobic interactions, thus reaching very high encapsulation efficiency. The size, morphology, and fluorescent properties of blank and drug-loaded micelles were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescent spectroscopy, respectively. Additionally, after 72 h of incubation, drug-loaded micelles released 3.25 μM of BzH, which was spectrophotometrically determined. The BzH drug-loaded micelles were found to exhibit enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, with long-lasting effects on microtubule organization, with apoptotic alterations and preferential localization in the perinuclear space of cancer cells. In contrast, the antitumor effect of BzH alone or incorporated in micelles on non-cancerous cells MCF-10A was relatively weak.

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“…The synthesized compounds were evaluated for anthelmintic activity against isolated T. spiralis muscle larvae (ML) according to an established protocol [ 10 , 21 ]. The antiparasitic drugs albendazole and ivermectin were used as standard references.…”

Section: Resultsmentioning

confidence: 99%

“…The parasitological experiments in vitro for anti- T. spiralis activity of the tested compounds 3a – f were performed as previously described [ 10 , 21 ].…”

Section: Methodsmentioning

confidence: 99%

Fused Triazinobenzimidazoles Bearing Heterocyclic Moiety: Synthesis, Structure Investigations, and In Silico and In Vitro Biological Activity

et al. 2023

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[1,3,5]Triazino[1,2-a]benzimidazole-2-amines bearing heterocyclic moiety in 4-position were synthesized. The compounds were characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, and HRMS spectroscopy. The molecular geometry and electron structure of these molecules were theoretically studied using density functional theory (DFT) methods. The molecular structure of the synthesized fused triazinobenzimidazole was confirmed to correspond to the 3,4-dihydrotriazinobenzimidazole structure through the analysis of spectroscopic NMR data and DFT calculations. The antinematodic activity was evaluated in vitro on isolated encapsulated muscle larvae (ML) of Trichinella spiralis. The results showed that the tested triazinobenzimidazoles exhibit significantly higher efficiency than the conventional drug used to treat trichinosis, albendazole, at a concentration of 50 μg/mL. The compound 3c substituted with a thiophen-2-yl moiety exhibited the highest anthelmintic activity, with a larvicidal effect of 58.41% at a concentration of 50 μg/mL after 24 h of incubation. Following closely behind, the pyrrole analog 3f demonstrated 49.90% effectiveness at the same concentration. The preliminary structure-anti-T. spiralis activity relationship (SAR) of the analogues in the series was discussed. The cytotoxicity of the benzimidazole derivatives against two normal fibroblast cells (3T3 and CCL-1) and two cancer human cell lines (MCF-7 breast cancer cells and chronic myeloid leukemia cells AR-230) was evaluated using the MTT-dye reduction assay. The screening results indicated that the compounds showed no cytotoxicity against the tested cell lines. An in silico study of the physicochemical and pharmacokinetic characteristics of the novel synthesized fused triazinobenzimidazoles showed that they were characterized by a significant degree of drug-likeness and optimal properties for anthelmintic agents.

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New 1H-benzimidazole-2-yl hydrazones with combined antiparasitic and antioxidant activity

Abstract: The design of new drug candidates that combine anthelmintic and antioxidant actions in one molecule offers a beneficial approach in the treatment of the tissue damages, immune system dysfunction and oxidative stress caused by trichinellosis.

Cited by 23 publications

References 73 publications

Radical Scavenging Mechanisms of 1-Arylhydrazone Benzimidazole Hybrids with Neuroprotective Activity

Radical Scavenging Mechanisms of 1-Arylhydrazone Benzimidazole Hybrids with Neuroprotective Activity

Novel Fluorescent Benzimidazole-Hydrazone-Loaded Micellar Carriers for Controlled Release: Impact on Cell Toxicity, Nuclear and Microtubule Alterations in Breast Cancer Cells

Fused Triazinobenzimidazoles Bearing Heterocyclic Moiety: Synthesis, Structure Investigations, and In Silico and In Vitro Biological Activity

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