In silico, NMR and pharmacological evaluation of an hydroxyoxindole cholinesterase inhibitor

Bacalhau, Patrícia; Fernandes, Luís; Martins, M. Rosário; Candeias, Fátima; Carreiro, Elisabete P.; López, Óscar; Caldeira, Ana Teresa; Totobenazara, Jane; Guedes, Rita C.; Burke, Anthony J.

doi:10.1016/j.bmc.2018.12.007

Cited by 11 publications

(4 citation statements)

References 24 publications

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“…The inhibitory activities of title compounds against commercially available cholinesterases (eeAChE) (Electrophorus electricus, Type V-S), eqBuChE (equine serum), were conducted using minor modifications of Ellman's assay [29,32]. Nine different concentrations (1.2, 2.4, 4.7, 9.4, 19.8, 37.5, 75, 150, and 300 µM in H 2 O:DMSO (50:50)) of each test compound were used to determine the enzyme-inhibition activity.…”

Section: In Vitro Cholinesterase Inhibitory Assaymentioning

confidence: 99%

Quercetin-1,2,3-Triazole Hybrids as Multifunctional Anti-Alzheimer’s Agents

Carreiro,

Costa,

Antunes

et al. 2023

Molecules

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The number of patients with Alzheimer’s disease (AD) continues to rise and, despite the efforts of researchers, there are still no effective treatments for this multifaceted disease. The main objective of this work was the search for multifunctional and more effective anti-Alzheimer agents. Herein, we report the evaluation of a library of quercetin-1,2,3-triazole hybrids (I–IV) in antioxidant, hydrogen peroxide-induced oxidative stress protection, and cholinesterases (AChE and BuChE) inhibitory activities. Hybrids IIf and IVa-d showed potent in vitro inhibitory activity on eqBuChE (IC50 values between 11.2 and 65.7 μM). Hybrid IIf, the best inhibitor, was stronger than galantamine, displaying an IC50 value of 11.2 μM for eqBuChE, and is also a competitive inhibitor. Moreover, toxicity evaluation for the most promising hybrids was performed using the Artemia salina toxicity assay, showing low toxicity. Hybrids IIf, IVb, and IVd did not affect viability at 12.5 μM and also displayed a protective effect against oxidative stress induced by hydrogen peroxide in cell damage in MCF-7 cells. Hybrids IIf, IVb, and IVd act as multifunctional ligands in AD pathologies.

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Section: In Vitro Cholinesterase Inhibitory Assaymentioning

confidence: 99%

Quercetin-1,2,3-Triazole Hybrids as Multifunctional Anti-Alzheimer’s Agents

Carreiro,

Costa,

Antunes

et al. 2023

Molecules

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“…1 H NMR (CDCl 3 , 600 MHz) δ H 6.70 (1H, t, J = 5.5 Hz, H-3′), 6.31 (1H, d, J = 2.9 Hz, H-13b), 5.84 (1H, d, J = 4.3 Hz, H-8), 5.62 (1H, d, J = 2.9 Hz, H-13a), 5.19 (1H, dd, J = 11.0, 5.6 Hz, H-1), 5.12 (1H, t, J = 9. 3…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Recently, natural product chemists have shown interest in the development of new in silico approaches for the rapid annotation of novel compounds and dereplication of the known ones from natural products. In silico methods for spectrometric data generated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), which are the two most popular techniques for characterizing natural products, are being developed. − Although high-resolution MS is the powerful technique for the measurement of tons of metabolites and production of their structural data in a short time, low reproducibility and interpretability have become the weak points for the accurate identification of compounds . Meanwhile, NMR spectroscopy guarantees higher reproducibility compared to MS, but it also needs to acquire expertise for the interpretation of 1D and 2D NMR data, which has become a big barrier for novice chemists in the fields of natural products.…”

Section: Introductionmentioning

confidence: 99%

Targeted Isolation of Cytotoxic Sesquiterpene Lactones from Eupatorium fortunei by the NMR Annotation Tool, SMART 2.0

et al. 2020

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Small Molecular Accurate Recognition Technology (SMART 2.0) has recently been introduced as a NMR-based machine learning tool for the discovery and characterization of natural products. We attempted targeted isolation of sesquiterpene lactones from Eupatorium fortunei with the aid of structural annotation by SMART 2.0 and chemical profiling. Eight germacrene-type ( 1–7 and 10 ) and two eudesmane-type sesquiterpene lactones ( 8 and 9 ) were isolated from the whole plant of Eupatorium fortunei . With the guidance of the results of the subfractions from E. fortunei obtained by SMART 2.0, their cytotoxic activities were evaluated against five cancer cells (SKOV3, A549, PC3, HEp-2, and MCF-7). Compounds 4 and 8 exhibited IC 50 values of 3.9 ± 1.2 and 3.9 ± 0.6 μM against prostate cancer cells, PC3, respectively. Compound 7 showed good cytotoxicity with IC 50 values of 5.8 ± 0.1 μM against breast cancer cells, MCF-7. In the present study, the rapid annotation of the mixture of compounds in a fraction by the NMR-based machine learning tool helped the targeted isolation of bioactive compounds from natural products.

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“…the atoms involved in the interaction. In the field of AD drug discovery, this powerful technique has been fruitfully applied to investigate the binding of known and potential cholinesterase inhibitors, such as galantamine[118], donepezil and donepezil-based hybrids[119,120], (S)-rivastigmine[121], gallic acid, scopoletin and 4-methylumbelliferone[122], as well as isoquinolone[118], 3-hydroxyoxindole[123] and coumarin derivatives[124]; in some of these studies,…”

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confidence: 99%