Abstract:
:Phenolic acids are ubiquitous antioxidants accounting for approximately one third of the phenolic compounds in our diet. Their importance was supported by epidemiological studies that suggest an inverse relationship between dietary intake of phenolic antioxidants and the occurrence of diseases, such as cancer and neurodegenerative disorders. However, until now, most of natural antioxidants have limited therapeutic success a fact that could be related with their limited distribution throughout the body and with the inherent difficulties to attain the target sites. The development of phenolic antioxidants based on a hybrid concept and structurally based on natural hydroxybenzoic (gallic acid) and hydroxycinnamic (caffeic acid) scaffolds seems to be a suitable solution to surpass the mentioned drawbacks. Galloyl-cinnamic hybrids were synthesized and their antioxidant activity as well as partition coefficients and redox potentials evaluated. The structure-property-activity relationship (SPAR) study revealed the existence of a correlation between the redox potentials and antioxidant activity. The galloyl-cinnamic acid hybrid stands out as the best antioxidant supplementing the effect of a blend of gallic acid plus caffeic acid endorsing the hypothesis that the whole is greater than the sum of the parts. In addition, some hybrid compounds possess an appropriate lipophilicity allowing their application as chain-breaking antioxidant in biomembranes or other type of lipidic systems. Their predicted ADME properties are also in accordance with the general requirements for drug-like compounds. Accordingly, these phenolic hybrids can be seen as potential antioxidants for tackling the oxidative status linked to the neurodegenerative, inflammatory or cancer processes.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Teixeira J,Silva T,Benfeito S,Gaspar A,Garrido EM,Garrido J,Borges Fdoi
10.1016/j.ejmech.2012.12.049subject
Has Abstractpub_date
2013-04-01 00:00:00pages
289-96eissn
0223-5234issn
1768-3254pii
S0223-5234(13)00005-6journal_volume
62pub_type
杂志文章abstract::In this study synthesis and β-glucuronidase inhibitory potential of 3/5/8 sulfonamide and 8-sulfonate derivatives of quinoline (1-40) are discussed. Studies reveal that all the synthetic compounds were found to have good inhibitory activity against β-glucuronidase. Nonetheless, compounds 1, 2, 5, 13, and 22-24 having ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.08.052
更新日期:2017-10-20 00:00:00
abstract::We report herein the synthesis of 5-substituted [1]pyrindine derivatives and the evaluation of their antiproliferative properties on HeLa cells, a cervical carcinoma tumor cell line, and on the melanoma A2058 cell line. The most efficient compounds display cytotoxicity against tumor cells in the micromolar range but h...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.11.028
更新日期:2010-03-01 00:00:00
abstract::Some novel pyrimidine-5-carbonitrile derivatives bearing various substituent have been synthesized. The structures of target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their cytotoxic potency against certain human tum...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.05.028
更新日期:2013-08-01 00:00:00
abstract::A series of icaritin derivatives bearing carboxylic acid or carboxylic ester groups are synthesized, and their in vitro cytotoxic activity against three cancer cell lines, MCF-7, MDA-MB-435s, and A549, are evaluated by MTT assay. Several derivatives including 2h, 2j, 5b and 5d show higher cytotoxic activity than the p...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.06.006
更新日期:2015-07-15 00:00:00
abstract::Rhinovirus (RV), member of the Enterovirus genus, is known to be involved in more than half of the common colds. Through advances in molecular biology, rhinoviruses have also been associated with exacerbations of chronic pulmonary diseases (e.g. asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis)...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.09.036
更新日期:2017-11-10 00:00:00
abstract::Lung cancer is one of the most malignant tumors with the highest morbidity and mortality. Most of them are non-small cell lung cancer (NSCLC). KRASG12C gene mutation is an important driving factor for NSCLC. However, the development of high-affinity inhibitors targeting KRASG12C mutants remains a daunting challenge. H...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.111844
更新日期:2020-01-01 00:00:00
abstract::A series of new imidazolidineiminothione derivatives with various halogenated and alkylated aromatic substituents at N-(1) and at N-(3) was synthesized through the reaction of N-arylcyanothioformamides with arylisocyanate derivatives. Structure of imidazolidineiminothione derivatives were established based on spectros...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.06.051
更新日期:2016-10-21 00:00:00
abstract::A series of 3-N-aryl substituted-2-heteroarylchromones was efficiently synthesized via Pd-mediated oxidative coupling under the influence of hetero-atoms neighboring group participation. Synthesized molecules were evaluated against human microtubule affinity regulating kinase 4 (MARK4) enzyme inhibitors, a recently id...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2018.09.030
更新日期:2018-11-05 00:00:00
abstract::A series of platinum(II) complexes of N-monoalkyl-1R,2R-diaminocylclohexanes with 3-(nitrooxy)cyclobutane-1,1-dicarboxylate as a leaving group were synthesized and characterized by elemental analysis, IR, (1)H, (13)C and (195)Pt NMR spectroscopy together with ESI-MS spectrometer. In vitro cytotoxicity study on these c...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.08.007
更新日期:2014-10-06 00:00:00
abstract::Pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X₃ receptor antagonists as potential antinociceptive agents. Based on the results of our previous report, all strong anionic groups in PPADS inc...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.10.026
更新日期:2013-01-01 00:00:00
abstract::A new series of substituted 8-fluro-4H-pyrimido[2,1-b] [1,3]benzothiazole-4-ones () substituted 7-methyl-4H-isoxazolo[2,3-a]pyrimidin-4-ones, and substituted 2-methyl-5,6,7,8-tetrahydro-9H-isoxazolo[2,3-a]pyridopyrimidin-9-ones, compounds I-VII, have been prepared via condensation of beta-keto esters with 2-aminopyrid...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2006.03.025
更新日期:2006-08-01 00:00:00
abstract::A new series of potential GABA uptake inhibitors starting from of 1H-imidazol-4-ylacetic acid with the carboxylic acid side chain originating from different positions and varying in length have been synthesized and tested for the inhibitory potency at the four GABA uptake transporters mGAT1-4 stably expressed in HEK c...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2011.01.042
更新日期:2011-05-01 00:00:00
abstract::A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues were synthesized, characterized ((1)H NMR, (13)C NMR and LCMS) and screened for their in vitro anti-tubercular and antibacterial activity. Many of these compounds exhibited MIC val...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.10.055
更新日期:2014-01-01 00:00:00
abstract::A nonlinear QSAR study was conducted on a series of 4-phenylpiperidine derivatives (4PPs) acting as mu opioid agonists by three-layer back-propagation neural network (NN) method. At first a variety of molecular descriptors were calculated and then selected with two-stage least squares combining partial least squares (...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2005.10.017
更新日期:2006-02-01 00:00:00
abstract::A series of 1,2,4-triazole-3-carboxamides has been prepared from alkyl-1,2,4-triazole-3-carboxylates under mild conditions. The ability of these triazoles to displace [3H]-CP55940 from CB1 cannabinoid receptor was measured. However, they showed only poor to moderate binding affinities, indicating that substitution of ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2005.06.012
更新日期:2006-01-01 00:00:00
abstract::beta-Thujaplicin (hinokitiol or 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), a natural tropolone, shows numerous activities while its synthetic analogues were found to exhibit anticancer and anti-ischemic activity. However, the ability of tropolone derivatives to protect neuronal cells from oxidative stress-ind...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.12.006
更新日期:2010-03-01 00:00:00
abstract::A series of quinoline-containing c-Met inhibitors were prepared and studied. Chemistry was developed to introduce a pyridyl moiety onto the 2-aryl ring present in a lead molecule which mitigated the potential for quinone formation relative to the original compound. The study also assessed the importance of an acylthio...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2007.08.011
更新日期:2008-06-01 00:00:00
abstract::Dihydrofolate reductase (DHFR) has been a well-recognized target for the treatment of many diseases. Based on 8,10-dideazaminopterins, which are classical antifolates that potently inhibit DHFR, we have designed a series of novel 2,4-diamino-6-substituted pyrido[3,2-d]pyrimidines. By removing the glutamate moiety and ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.01.033
更新日期:2017-03-10 00:00:00
abstract::Alzheimer's disease (AD) is associated with multifactorial neuropathological conditions, which include cholinergic deficit, amyloid-beta plaques formation, loss of neuronal plasticity and neuronal death. Treating such multifactorial conditions with a single target directed approach is considered to be inadequate. Acco...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.111613
更新日期:2019-11-15 00:00:00
abstract::Several myrcenylhydroquinone derivatives have been evaluated for their cytotoxic activity against three neoplastic cell line cultures and compared with the activity previously observed on other neoplastic systems. Also a new series of this type of compounds has been prepared and the compounds synthesised have been eva...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0223-5234(01)01329-0
更新日期:2002-02-01 00:00:00
abstract::Among the EGFRs, HER2 is a major heterodimer partner and also has important implications in the formation of particular tumors. Interaction of HER2 protein with other EGFR proteins can be modulated by small molecule ligands and, hence, these protein-protein interactions play a key role in biochemical reactions related...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.04.038
更新日期:2013-07-01 00:00:00
abstract::A series of 1H,3H-thiazolo[4,3-b]quinazolines (2a-i) were synthesized and evaluated for their in vitro antitumour activity against ca. 60 human tumour cell lines. They exhibited moderate (2c, 2d, 2f and 2g) to strong (2a, 2b, 2e, 2h and 2i) cell-growth inhibition at a concentration of 10(-4) M, but weak activity at lo...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0223-5234(00)01195-8
更新日期:2000-12-01 00:00:00
abstract::A series of pleuromutilin derivatives bearing piperazine ring have been reported. The in vitro antibacterial activities of the synthetic derivatives against MRSA (ATCC 43300), Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212), Enterococcus faecium (ATCC35667) and Escherichia coli (ATCC25922) were ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.01.004
更新日期:2017-02-15 00:00:00
abstract::Hepatitis B is a vaccine-preventable, but potentially life-threatening liver infection caused by the Hepatitis B virus (HBV). It represents an important health burden, with 257 million active cases globally. Current HBV treatments using nucleos(t)ide analogs and pegylated interferons cannot alleviate the situation com...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2020.112714
更新日期:2020-11-15 00:00:00
abstract::We report the design and synthesis of a series of dipeptide-type inhibitors with novel P3 scaffolds that display potent inhibitory activity against SARS-CoV 3CLpro. A docking study involving binding between the dipeptidic lead compound 4 and 3CLpro suggested the modification of a structurally flexible P3 N-(3-methoxyp...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.07.037
更新日期:2013-10-01 00:00:00
abstract::The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2018.09.072
更新日期:2018-12-05 00:00:00
abstract::We describe a novel class of β-carboline alkaloid-peptide conjugates that possess both free radical scavenging and thrombolytic activity. These conjugates demonstrate therapeutic efficacy in a rat arterial thrombosis assay, as well as free radical scavenging capacity as evaluated in a PC12 cell survival assay. Our res...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2011.01.021
更新日期:2011-05-01 00:00:00
abstract::A series of novel indole derivatives was designed and synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). The most potent compound 14c was identified with an IC50 value of 0.10 μM by testing the inhibitory activity against recombinant human FBPase. The structure-activity relationships were investigated ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.11.049
更新日期:2015-01-27 00:00:00
abstract::Novel diarylpyrimidines (DAPY), which represent next generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus type I (HIV-1) assessed. Modulations at positions 2 and 6 of the left phenyl ring generated interesting derivatives of ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2006.11.014
更新日期:2007-05-01 00:00:00
abstract::In an attempt to discover new potent inhibitors for Mycobacterium tuberculosis (Mtb), a series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed by considering Lipinski rule. The designed compounds were synthesized, characterized and evaluated for their ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.08.054
更新日期:2013-11-01 00:00:00