Synthesis and biological evaluation of pyridazino[1′,6′:1,2]pyrido[3,4-b]indolinium and pyridazino[1,6-a]benzimidazolium salts as anti-inflammatory agents

Rodríguez-Sanz, Aranzazu; Sánchez‐Alonso, Patricia; Bellón, Teresa; Alajarı́n, Ramón; Martínez, Virginia; Selgas, Rafael; Vaquero, Juan J.; Alvárez‐Builla, Julio

doi:10.1016/j.ejmech.2015.01.060

Cited by 11 publications

(7 citation statements)

References 25 publications

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“…[7] These ligands are able to form stable complexes with almost all of the transition metals. In recent years, many studies have been reported on the biological activities of NHC precursors such as anticancer, [8] antimicrobial, [9] cytotoxicity, [10] antibiofilm, [11] antioxidant, [12] antifungal, [13] anti-inflammatory, [14] and antiviral. [15] Furthermore, the enzyme inhibition activities of benzimidazolium salts are also noteworthy.…”

Section: Introductionmentioning

confidence: 99%

Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and α‐glycosidase

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et al. 2022

J Biochem & Molecular Tox

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Here, we report the synthesis, characterization, and biological activities of a series of benzimidazolium salts bearing the trifluoromethylbenzyl group. All benzimidazolium salts were characterized by using nuclear magnetic resonance (NMR) ( 1 H NMR and 13 C NMR), Fourier transform-infrared spectroscopy, and elemental analysis techniques. The crystal structures of some of these compounds were obtained by the single-crystal X-ray diffraction method. Furthermore, the acetylcholinesterase (AChE) and α-glycosidase (α-Gly) enzyme inhibition activities of these compounds were investigated. The obtained results revealed that 2e, with K i value of 1.36 ± 0.34 µM against AChE and 3d with K i value of 91.37 ± 10.38 µM against α-Gly, were the most potent compounds against both assigned enzymes. It should be noted that most of the synthesized compounds were more potent than standard inhibitor tacrine (TAC) against AChE. In silico studies, we focused on compound 2e, 3d, 3e, and 3f as potent inhibitors of AChE and α-Gly, the compound 2e showed good binding energy (−10.23 kcal/mol), among the three selected compounds and positive control (−10.18, −10.08, and −7.37 kcal/mol for 3d, 3f, and TAC, respectively). Likewise, as a result of the same compounds against the α-Gly enzyme, the compound 3d had the highest binding affinity (−8.39 kcal/mol) between the four selected compounds and the positive control (−8.27, −8.10, −8.06, and −7.53 kcal/mol for 3f, 3e, 2e, and acarbose, respectively). From the absorption, distribution, metabolism, excretion, and toxicity analyses, it can be concluded that the compounds under consideration exhibited more drug-likeness properties in the prediction studies compared to positive controls.

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Section: Introductionmentioning

confidence: 99%

Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and α‐glycosidase

Tezcan

Gök

Sevinçek

et al. 2022

J Biochem & Molecular Tox

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“… Reagents and conditions: (a) 493 MesSO 3 NH 2 , DCM, 1 h; (b) acenaphthoquinone, NaOAc, EtOH, reflux, 1 h; (c) 333 hν (254 nm, 6 × 8 W), 48–72 h; (d) 494 R′C≡CH, CuI (10 mol %), 1,10-phenanthroline (20 mol %), Cs 2 CO 3 (1 equiv), dioxane, 100 °C, 26–32 h. …”

Section: Nonbenzenoid Fusionmentioning

confidence: 99%

“…This nitrogen-rich polyaromatic skeleton showed a reversible reduction wave in cyclic voltammetry, corresponding to an estimated LUMO level of −3.59 eV (see Scheme , Section ). In 2017, the preparation of the nitrogen-rich 262.2 from a pyrrolo[3,2- d ]pyrimidine-based diamine was reported by Popov et al Bellón and Alajarín et al reported the preparation of the new acenaphtho- and indolo-fused quinolizinium salt 262.5 using the base-induced condensation of the N- aminopyridinium salt 262.4 with acenaphthoquinone . This transformation relied on the CH acidity of the vicinal methyl group in 262.4 .…”

Section: Nonbenzenoid Fusionmentioning

confidence: 99%

Recent Advances in Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds

et al. 2021

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“…Benzimidazolium salts (derived from benzimidazole) have been extensively explored the for design and discovery of new drugs [ 12 , 13 , 14 ]. Particularly, in organometallic chemistry, benzimidazolium salts have emerged as an influential class of ligands due to strong σ-donor and weak π-accepting ability.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Amide-Functionalized Benzimidazolium Salts as Potent α-Glucosidase Inhibitors

et al. 2021

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α-Glucosidase inhibitors (AGIs) are used as medicines for the treatment of diabetes mellitus. The α-Glucosidase enzyme is present in the small intestine and is responsible for the breakdown of carbohydrates into sugars. The process results in an increase in blood sugar levels. AGIs slow down the digestion of carbohydrates that is helpful in controlling the sugar levels in the blood after meals. Among heterocyclic compounds, benzimidazole moiety is recognized as a potent bioactive scaffold for its wide range of biologically active derivatives. The aim of this study is to explore the α-glucosidase inhibition ability of benzimidazolium salts. In this study, two novel series of benzimidazolium salts, i.e., 1-benzyl-3-{2-(substituted) amino-2-oxoethyl}-1H-benzo[d]imidazol-3-ium bromide 9a–m and 1-benzyl-3-{2-substituted) amino-2-oxoethyl}-2-methyl-1H-benzo[d] imidazol-3-ium bromide 10a–m were screened for their in vitro α-glucosidase inhibitory potential. These compounds were synthesized through a multistep procedure and were characterized by 1H-NMR, 13C-NMR, and EI-MS techniques. Compound 10d was identified as the potent α-glucosidase inhibitor among the series with an IC50 value of 14 ± 0.013 μM, which is 4-fold higher than the standard drug, acarbose. In addition, compounds 10a, 10e, 10h, 10g, 10k, 10l, and 10m also exhibited pronounced potential for α-glucosidase inhibition with IC50 value ranging from 15 ± 0.037 to 32.27 ± 0.050 µM when compared with the reference drug acarbose (IC50 = 58.8 ± 0.12 μM). A molecular docking study was performed to rationalize the binding interactions of potent inhibitors with the active site of the α-glucosidase enzyme.

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Synthesis and biological evaluation of pyridazino[1′,6′:1,2]pyrido[3,4-b]indolinium and pyridazino[1,6-a]benzimidazolium salts as anti-inflammatory agents

Cited by 11 publications

References 25 publications

Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and α‐glycosidase

Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and α‐glycosidase

Recent Advances in Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds

Discovery of Amide-Functionalized Benzimidazolium Salts as Potent α-Glucosidase Inhibitors

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