Natural dimers of coumarin, chalcones, and resveratrol and the link between structure and pharmacology

Menezes, José C. J. M. D. S.; Diederich, Marc

doi:10.1016/j.ejmech.2019.111637

Cited by 52 publications

(24 citation statements)

References 113 publications

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“…From a structural point of view, the coumarins are classified in different chemical classes (simple coumarins, fused polycyclic coumarins, phenylcoumarins, biscoumarins, and so on) 1,2 . The existence of an extensive library of coumarins from (semi)synthetic source has been triggered by the high versatility of benzo-a-pyrone system to be an excellent scaffold to perform structural modifications [3][4][5][6] . Moreover, the chemical diversity of the coumarin system implies that they might play an important role in medicinal chemistry for drug discovery processes, so that many coumarins are used currently in drug development as vitamin K antagonists, choleretic and antibacterial and antiviral agents [7][8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

Mancuso

Luca

Angeli

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable b-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft.

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Section: Introductionmentioning

confidence: 99%

Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

Mancuso

Luca

Angeli

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…There have been reports on natural chalcones that form several dimeric forms and act as anti-viral or anti-cancer agents [ 23 , 24 ]. The spatial arrangement of aromatic rings in such dimeric structures includes hydroxyl groups which may allow them to have better interaction with amino acid residues of proteins or enzymes [ 25 ]. Therefore, to support our experimental findings, a series of calculations related to different arrangements of CA molecules (i.e., monomer and seven dimers) was performed (see Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…The chemical structure and atom numbering are presented in Scheme 1. Cardamonin is found in cardamom spice and possesses various pharmacological properties including anticancer effects due to the cell apoptosis caused in nasopharyngeal carcinoma, prostate cancer and triple-negative breast cancer cells [9,10], inhibition of tumour incidence, tumour multiplicity, Ki-67 and Molecules 2020, 25, 4070 of β-catenin positive cells [11,12]. In addition, cardamonin exhibits antinociceptive effects in mice through the involvement of TRPV 1 , glutamate and opioid receptors [13].…”

Section: Introductionmentioning

confidence: 99%

Structure and Physical Properties of Cardamonin: A Spectroscopic and Computational Approach

2020

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This is the first study of the crystal structure of cardamonin (CA) confirmed using single-crystal XRD analysis. In the crystal lattice of CA, two symmetry independent molecules are linked by hydrogen bonds within the layers and by the π···π stacking interactions in the columns which lead to the occurrence of two types of conformations among the CA molecules in the crystal structure. To better understand the stability of these arrangements in both crystals and the gaseous phase, seven different CA dimers were theoretically calculated. The molecular structures were optimized using density functional theory (DFT) at the B3LYP/6–311G+(d,p) level and the spectroscopic results were compared. It was found that the calculated configurations of dimer I and III were almost identical to the ones found in the CA crystal lattice. The calculated UV-Vis spectra for the CA monomer and dimer I were perfectly consistent with the experimental spectroscopic data. Furthermore, enhanced emissions induced by aggregated CA molecules were registered in the aqueous solution with the increase of water fractions. The obtained results will help to further understand the relation between a variety of conformations and the biological properties of CA, and the results are also promising in terms of the applicability of CA as a bioimaging probe to monitor biological processes.

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“…This structural feature provides an increase in reaction selectivity and, in terms of molecule-protein recognition, identical interactions would take place on each symmetrical portion of the molecule. As with dimeric secondary metabolites present in plants that manifest inhibition to tyrosinase enzyme [56], we prepared hydroxylated biphenyls 14-20 bearing functional groups that use the chemical space effectively by increasing the structural complexity and providing more interactions with amino acid residues.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Studies of the Inhibitory Effect of Hydroxylated Phenylpropanoids and Biphenols Derivatives on Tyrosinase and Laccase Enzymes

et al. 2020

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The impaired activity of tyrosinase and laccase can provoke serious concerns in the life cycles of mammals, insects and microorganisms. Investigation of inhibitors of these two enzymes may lead to the discovery of whitening agents, medicinal products, anti-browning substances and compounds for controlling harmful insects and bacteria. A small collection of novel reversible tyrosinase and laccase inhibitors with a phenylpropanoid and hydroxylated biphenyl core was prepared using naturally occurring compounds and their activity was measured by spectrophotometric and electrochemical assays. Biosensors based on tyrosinase and laccase enzymes were constructed and used to detect the type of protein-ligand interaction and half maximal inhibitory concentration (IC50). Most of the inhibitors showed an IC50 in a range of 20–423 nM for tyrosinase and 23–2619 nM for laccase. Due to the safety concerns of conventional tyrosinase and laccase inhibitors, the viability of the new compounds was assayed on PC12 cells, four of which showed a viability of roughly 80% at 40 µM. In silico studies on the crystal structure of laccase enzyme identified a hydroxylated biphenyl bearing a prenylated chain as the lead structure, which activated strong and effective interactions at the active site of the enzyme. These data were confirmed by in vivo experiments performed on the insect model Tenebrio molitur.

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Natural dimers of coumarin, chalcones, and resveratrol and the link between structure and pharmacology

Cited by 52 publications

References 113 publications

Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

Structure and Physical Properties of Cardamonin: A Spectroscopic and Computational Approach

Synthesis and Studies of the Inhibitory Effect of Hydroxylated Phenylpropanoids and Biphenols Derivatives on Tyrosinase and Laccase Enzymes

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