Synthesis and biological evaluation of new 2-(6-alkyl-pyrazin-2-yl)-1H-benz[d]imidazoles as potent anti-inflammatory and antioxidant agents

Shankar, B.; Pochampally, Jalapathi; Valeru, Anil; Kumar, Angajala Kishor; Balabadra, Saikrishna; Kudle, Karunakar Rao

doi:10.1007/s00044-017-1897-7

Cited by 22 publications

(14 citation statements)

References 22 publications

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“…[8,9] Azoles possessed distinct structural importance due to their capability of making hydrogen bonds and other non-covalent interactions with target sites of various enzymes. These small heterocyclic moieties are incorporated in structural framework of different anti-proliferative, [10] anti-inflammatory, [11,12] anticancer, [13,14] antimicrobial, [15] anti-tubercular agents. [16,17] Many nitrogen atom containing azolic templates have recently been reported as antiurease agents as well.…”

Section: Introductionmentioning

confidence: 99%

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

et al. 2020

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Towards discovery of effective urease inhibitors; we disclose here a hybrid series of imidazole and pyrazole motifs as potent antiurease agents. A para-toluenesulfonic acid (TsOH) catalyzed, facile synthetic approach was employed for the preparation of targeted molecular designs in good yields upto 94 %. The novel scaffolds were characterized by different spectroscopic means (FTIR, NMR, and Mass spectrometry) and elemental analysis helped to identify the purity of these compounds. Afterwards, the derivatives was tested against Jack bean's urease enzyme to explore their inhibiting potencies. All analogues (4 a-4 l) were found active against the studied enzyme in comparison with the standard drug thiourea (IC 50 = 21.26 � 0.12 μM). However, following dibromo substituted derivatives: 4 f, 4 g, 4 h, 4 i, 4 j, 4 k, and 4 l were surfaced out as potent urease inhibitors among the series. The identified lead candidates were meta-nitro substituted 4 k with IC 50 = 0.7 � 0.002 μM and a para-nitro containing compound 4 l with IC 50 = 1.0 � 0.003 μM. As observed in docking calculations, ionic and hydrogen bonding, π-stacking, interaction with nickel ions and other hydrophobic interactions probably stabilized the ligand bindings at the active site of urease.

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Section: Introductionmentioning

confidence: 99%

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

et al. 2020

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“…[ 11 ]. Literature survey revealed that of the compounds attitude benzimidazole moites reported to possess a number of attractive biological activities such as anti tubercular, anticancer, antihelmintic, anti allergic [ 12 ], antihistaminic [ 13 ], antifungal [ 14 – 16 ] and anti-inflammatory [ 17 ]. Recently, Thomas et al reported that some novel 2-phenyl benzimidazole were shown cell based assays for cytotoxicity and antiviral activity against the panel of RNA and DNA virus molecules which have been found to be more potent [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, anti-microbial activity, cytotoxicity of some novel substituted (5-(3-(1H-benzo[d]imidazol-2-yl)-4-hydroxybenzyl)benzofuran-2-yl)(phenyl)methanone analogs

Shankar

Pochampally

Balabadra

et al. 2018

Chemistry Central Journal

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148

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BackgroundThere is a dire need for the discovery and development of new antimicrobial agents after several experiments for a better resistance of microorganisms towards antimicrobial agents become a serious health problem for a few years in the past. As benzimidazole possess various types of biological activities, it has been synthesized, in the present study, a new series of (5-(3-(1H-benzo[d]imidazol-2-yl)-4-hydroxybenzyl)benzofuran-2-yl)(phenyl)methanone analogs by using the condensation and screened for its in vitro antimicrobial activity and cytotoxicity.ResultsThe synthesized (5-(3-(1H-benzo[d]imidazol-2-yl)-4-hydroxybenzyl) benzofuran-2-yl)(phenyl)methanone analogs were confirmed by IR, 1H and 13C-NMR, MS spectra and HRMS spectral data. The synthesized compounds were evaluated for their in vitro antimicrobial potential against Gram-positive (Bacillus subtilis, Bacillus megaterium, Staph aureus and Streptococcus pyogenes), Gram-negative (Escherichia coli, Proteus vulgaris, Proteus mirabilis and Enterobacter aerogenes) bacterial and fungal (Aspergillus niger, Candida albicans, Fusarium oxysporum, Fusarium solani) strains by disc diffusion method and the minimum inhibitory concentration (MIC) in which it has been recorded in microgram per milliliter in comparison to the reference drugs, ciprofloxacin (antibacterial) and nystatin (antifungal). Further, the cytotoxicity (IC50 value) has also been assessed on human cervical (HeLa), Supt1 cancer cell lines by using MTT assay.ConclusionsThe following screened compounds (4d), (4f), (4g), (4k), (4l), (4o) and (4u) were found to be the best active against all the tested bacterial and fungal strains among all the demonstrated compounds of biological study. The MIC determination was also carried out against bacteria and fungi, the compounds (4f) and (4u) are found to be exhibited excellent potent against bacteria and fungi respectively. The compounds (4f) and (4u) were shown non-toxic in nature after screened for cytotoxicity against the cancer cell lines of human cervical (HeLa) and Supt1. Additionally, structure and antibacterial activity relationship were also further supported by in silico molecular docking studies of the active compounds against DNA topoisomerase. Electronic supplementary materialThe online version of this article (10.1186/s13065-017-0364-3) contains supplementary material, which is available to authorized users.

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“…According to the bioactivity scores, the most promising compounds were found to be I30, I31, I33, and I34 with scores of 0.24, 0.32, 0.21, and 0.72, respectively, as an enzyme inhibitor suggesting COX enzyme may be involved in mediating this anti-inflammatory effect that correlated well with Shankar et al, Bukhari et al, Nascimento et al and Rocha et al studies. 45 , 48–50 On the contrary, Katikireddy et al believed that compound I32 works by inhibiting the COX-2 enzyme, however, the target prediction did not show a promising bioactivity score at this target suggesting computational studies should not be used solely for target predictions. 47 …”

Section: Target Predictions Of Selected Imidazole Derivativesmentioning

confidence: 99%

“… 45 , 48–50 On the contrary, Katikireddy et al believed that compound I32 works by inhibiting the COX-2 enzyme, however, the target prediction did not show a promising bioactivity score at this target suggesting computational studies should not be used solely for target predictions. 47 …”

Section: Target Predictions Of Selected Imidazole Derivativesmentioning

confidence: 99%

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Imidazole as a Promising Medicinal Scaffold: Current Status and Future Direction

Alghamdi¹,

Suliman²,

Almutairi³

et al. 2021

DDDT

100

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Various imidazole-containing compounds have been tested for their medical usefulness in clinical trials for several disease conditions. The rapid expansion of imidazole-based medicinal chemistry suggests the promising and potential therapeutic values of imidazole-derived compounds for treating incurable diseases. Imidazole core scaffold contains three carbon atoms, and two nitrogen with electronic-rich characteristics that are responsible for readily binding with a variety of enzymes, proteins, and receptors compared to the other heterocyclic rings. Herein, we provide a thorough overview of the current research status of imidazole-based compounds with a wide variety of biological activities including anti-cancer, anti-microbial, anti-inflammatory and their potential mechanisms including topoisomerase IIR catalytic inhibition, focal adhesion kinase (FAK) inhibition, c-MYC G-quadruplex DNA stabilization, and aurora kinase inhibition. Additionally, a great interest was reported in the discovery of novel imidazole compounds with anti-microbial properties that break DNA double-strand helix and inhibit protein kinase. Moreover, anti-inflammatory mechanisms of imidazole derivatives include inhibition of COX-2 enzyme, inhibit neutrophils degranulation, and generation of reactive oxygen species. This systemic review helps to design and discover more potent and efficacious imidazole compounds based on the reported derivatives, their ADME profiles, and bioavailability scores that together aid to advance this class of compounds.

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Synthesis and biological evaluation of new 2-(6-alkyl-pyrazin-2-yl)-1H-benz[d]imidazoles as potent anti-inflammatory and antioxidant agents

Cited by 22 publications

References 22 publications

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

Synthesis, anti-microbial activity, cytotoxicity of some novel substituted (5-(3-(1H-benzo[d]imidazol-2-yl)-4-hydroxybenzyl)benzofuran-2-yl)(phenyl)methanone analogs

Imidazole as a Promising Medicinal Scaffold: Current Status and Future Direction

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