Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues

Matysiak, Joanna; Skrzypek, Alicja; Karpińska, Monika; Czarnecka, Kamila; Szymański, Paweł; Bajda, Marek; Niewiadomy, Andrzej

doi:10.3390/biom9120870

Cited by 17 publications

(11 citation statements)

References 46 publications

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“…The obtained results confirm the broad spectrum of biological activity of the compounds, taking into account both the literature reports on the biological activity of benzo(naphtho)xazoles [ 2 , 20 , 22 ] and the results obtained by our team so far—resorcinol-azole conjugates [ 41 , 42 , 48 ].…”

Section: Discussionsupporting

confidence: 88%

“…Some benzimidazoleresorcinol conjugates inhibited in vitro self-induced Aβ (1–42) aggregation, and showed antioxidant properties. The molecular modelling studies exhibited, among others, that the hydroxyl groups and the heterocyclic ring participate in the crucial interactions (hydrogen bonds and π-π stacking) with AChE [ 41 ]. Therefore, it seems justified to assess the activity of compounds which, instead of the –NH– group, contain an isosteric oxygen atom.…”

Section: Introductionmentioning

confidence: 99%

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Cholinesterases Inhibition, Anticancer and Antioxidant Activity of Novel Benzoxazole and Naphthoxazole Analogs

et al. 2022

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Benzoxazole and naphthoxazole fused systems are found in many biologically active molecules. Novel benzoxazole and naphthoxazole analogs functionalized by the 2,4-dihydroxyphenyl moiety were designed, obtained and evaluated as a broad spectrum of biological potency compounds. Sulfinylbis[(2,4-dihydroxyphenyl)methanethione] or its analogs and 2-aminophenols or 1-amino-2-naphthol were used as starting reagents. 4-(Naphtho[1,2-d][1,3]oxazol-2-yl)benzene-1,3-diol was identified as the most promising compound of the nanomolar activity against AChE (IC50 = 58 nM) of the mixed-type inhibition and of the moderate activity against BChE (IC50 = 981 nM). The higher antiproliferative potency against a panel of human cancer cell lines for naphtho[1,2-d][1,3]oxazoles than for benzoxazoles was found. The activity of the analog with chlorine atom was in the range of 2.18–2.89 µM (IC50) against all studied cells and it is similar to that of cisplatin studied comparatively. Moreover, this compound was not toxic at this concentration to human normal breast cells and keratinocytes. For some compounds it also has proved antioxidant properties at the level of IC50 = 0.214 µM, for the most active compound. The lipophilicity of all compounds, expressed as log p values, is within the range recommended for potential drugs. The biological activity profile of the considered analogs and their lipophilic level justify the search for agents used in AD or in anticancer therapy in this group of compounds.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Cholinesterases Inhibition, Anticancer and Antioxidant Activity of Novel Benzoxazole and Naphthoxazole Analogs

et al. 2022

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“…In this regard, small organic molecules of a certain chemical architecture, in which the phenolic scaffold is attached directly to the azaheterocyclic backbone, can be considered as promising drug candidates for the treatment of socially significant diseases, such as neurodegenerative, cardiovascular, oncological diseases, etc. In particular, one can observe a few examples of 2H-imidazole-derived phenolic compounds of practical interest such as a Mcl-1/Bcl-2 dual inhibitor that effectively induces apoptosis in a dosedependent, mechanism-based manner in multiple cancer cell lines, an acetylcholinesterase inhibitor (AChE), and a phenolic alkaloid derived from the plant Dracocephalum heterophyllum (Figure 2) [34][35][36]. Meanwhile, functional derivatives of polyphenols deserve also a special attention in pharmaceutical chemistry due to a variety of biological activities, such as antitumor, antiviral, and anti-inflammatory ones [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds—A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes

et al. 2021

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The synthesis of inhibitors for oxidative stress-associated destructive processes based on 2H-imidazole-derived phenolic compounds affording the bifunctional 2H-imidazole-derived phenolic compounds in good-to-excellent yields was reported. In particular, a series of bifunctional organic molecules of the 5-aryl-2H-imidazole family of various architectures bearing both electron-donating and electron-withdrawing substituents in the aryl fragment along with the different arrangements of the hydroxy groups in the polyphenol moiety, namely derivatives of phloroglucinol, pyrogallol, hydroxyquinol, including previously unknown water-soluble molecules, were studied. The structural and antioxidant properties of these bifunctional 5-aryl-2H-imidazoles were comprehensively studied. The redox transformations of the synthesized compounds were carried out. The integrated approach based on single and mixed mechanisms of antioxidant action, namely the AOC, ARC, Folin, and DPPH assays, were applied to estimate antioxidant activities. The relationship “structure-antioxidant properties” was established for each of the antioxidant action mechanisms. The conjugation effect was shown to result in a decrease in the mobility of the hydrogen atom, thus complicating the process of electron transfer in nearly all cases. On the contrary, the conjugation in imidazolyl substituted phloroglucinols was found to enhance their activity through the hydrogen transfer mechanism. Imidazole-derived polyphenolic compounds bearing the most electron-withdrawing functionality, namely the nitro group, were established to possess the higher values for both antioxidant and antiradical capacities. It was demonstrated that in the case of phloroglucinol derivatives, the conjugation effect resulted in a significant increase in the antiradical capacity (ARC) for a whole family of the considered 2H-imidazole-derived phenolic compounds in comparison with the corresponding unsubstituted phenols. Particularly, conjugation of the polyphenolic subunit with 2,2-dimethyl-5-(4-nitrophenyl)-2H-imidazol-4-yl fragment was shown to increase ARC from 2.26 to 5.16 (104 mol-eq/L). This means that the considered family of compounds is capable of exhibiting an antioxidant activity via transferring a hydrogen atom, exceeding the activity of known natural polyphenolic compounds.

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“…Compound substituted with electron withdrawing groups showed the highest inhibitory action. Therefore, compound ST08 and ST09 are strongest inhibitor at the same time analogue ST09 is more active against BuchE 26 .…”

Section: Scheme 12mentioning

confidence: 89%

A systematic review on diverse synthetic route and pharmacological activities of benzimidazole as optimized lead

Thapa¹,

NARGUND²,

Biradar³

2022

juc

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The aim of this review is to provide the systematic information of synthetic scheme and biological activity of synthesized benzimidazole derivatives. Benzimidazole is widely used lead molecule for the synthesis of various types of pharmacologically active moiety. It is heterocyclic aromatic fused colorless solid having molecular mass of 118.053 g/mol. It is basic in nature and can be served as ligand in coordination chemistry. It is bioactive compound showed various pharmacological activity till now viz. anthelmintics (albendazole, mebendazole), proton pump inhibitors (omeprazole, pantoprazole), antibiotics, antiprotozoal, antifungal, anticancer, anti-viral, anti-oxidant, anti-inflammatory etc. Various synthetic route by various methods is also already reported. Some of them are traditional convenient method, microwave reactor method, solvent free synthesis method, green synthesis method. Due to its wide variety of biological action and the similarity with biomolecule, it is frequently taken as lead for new drug discovery

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Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues

Cited by 17 publications

References 46 publications

Cholinesterases Inhibition, Anticancer and Antioxidant Activity of Novel Benzoxazole and Naphthoxazole Analogs

Cholinesterases Inhibition, Anticancer and Antioxidant Activity of Novel Benzoxazole and Naphthoxazole Analogs

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds—A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes

A systematic review on diverse synthetic route and pharmacological activities of benzimidazole as optimized lead

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