Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer

Chen, Kuan‐Chung; Chen, Hsin‐Yi; Chen, Calvin Yu-Chian

doi:10.1155/2014/436863

Cited by 5 publications

(3 citation statements)

References 46 publications

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“…Many previous studies (Chen et al, 2014 , Chen, 2015 ; Huang et al, 2014 ; Hung et al, 2014 ) confirmed that the highest dock score obtained by molecular docking does not mean that the compound is a potent lead, but, to validate this result it is necessary to be accompanied by molecular dynamics simulations.…”

Section: Resultsmentioning

confidence: 95%

Discovery of potential SARS-CoV 3CL protease inhibitors from approved antiviral drugs using: virtual screening, molecular docking, pharmacophore mapping evaluation and dynamics simulation

Daoud

Mesli

Melkemi

et al. 2021

Journal of Biomolecular Structure and Dynamics

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The spread of corona-virus disease 2019 (COVID-19) has been faster than any other corona-viruses that have succeeded in crossing the animal-human barrier. This disease, caused by the severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2/2019-nCoV) posing a serious threat to global public health and local economies. There are three responsible for this disease; SARS-CoV-2, SARS-CoV and MERS-CoV. Whereas our goal is to test the affinity for a new class of compounds obtained from a hybridization of Chloroquine, Amodiaquine and Mefloquine with three targets SARS-CoV-2, SARS-CoV and MERS-CoV, in order to find new compounds as new inhibitors against Covid-19. In this work, we first used: the molecular docking/dynamics methods and ADME properties to study interaction and affinity between eight new compounds against three targets involved in the Covid-19. The results of the docking simulations and dynamics revealed that inhibitor of the malaria (Ligand 87) has an affinity to interact with SARS-CoV-2, SARS-CoV and MERS-CoV targets and they can be good inhibitors for treatment of Covid-19. Moreover, they give best affinity compared to the Remdesivir and Chloroquine and other clinical tests. The Pharmacokinetics was justified by means of lipophilicity and high coefficient of skin permeability. The in silico evaluation of ADME and drug-likeness revealed that L87 has higher absorption in the intestines with good bioavailability. However, an additional in vitro and/or in vivo experimental study should make it possible to verify the theoretical results obtained in silico. Communicated by Ramaswamy H. Sarma

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Section: Resultsmentioning

confidence: 95%

Discovery of potential SARS-CoV 3CL protease inhibitors from approved antiviral drugs using: virtual screening, molecular docking, pharmacophore mapping evaluation and dynamics simulation

Daoud

Mesli

Melkemi

et al. 2021

Journal of Biomolecular Structure and Dynamics

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“…The lengths of these hydrogen bonds are provided in Table 3, and Van der Waals', hydrogen bond, desolvation, and intermolecular energies are listed in Table 4. Several reports have checked best docking scores complex by molecular dynamics (MD) simulation [42][43][44][45][46]. Thus, we performed 50 ns MD simulations on indirubin and dehydroevodiamine to evaluate the stabilities of complexes and investigate possible ligand binding modes.…”

Section: Resultsmentioning

confidence: 99%

Biocomputational Screening of Natural Compounds against Acetylcholinesterase

et al. 2021

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Alzheimer’s disease (AD) is the most common form of dementia and is characterized by irreversible and progressive neurodegeneration. Cholinergic dysfunction has been reported in AD, and several cholinesterase inhibitors, including natural compounds and synthetic analogs, have been developed to treat the disease. However, there is currently no treatment for AD, as most drug-like compounds have failed in clinical trials. Acetylcholinesterase (AChE) is the target of most drugs used commercially to treat AD. This work focused on screening natural compounds obtained from the ZINC database (224, 205 compounds) against AChE to identify those possibly capable of enabling the management of AD. Indirubin and dehydroevodiamine were the best potential AChE inhibitors with free binding energies of −10.03 and −9.00 kcal/mol, respectively. The key residue (His447) of the active site of AChE was found to participate in complex interactions with these two molecules. Six H-bonds were involved in the ‘indirubin–AChE’ interaction and three H-bonds in the ‘dehydroevodiamine–AChE’ interaction. These compounds were predicted to cross the blood–brain barrier (BBB) and to exhibit high levels of intestinal absorption. Furthermore, ‘indirubin–AChE’ and ‘dehydroevodiamine–AChE’ complexes were found to be stable, as determined by root mean square deviation (RMSD) during a 50 ns molecular dynamics simulation study. Based on the free binding energies and stabilities obtained by simulation studies, we recommend that experimental studies be undertaken on indirubin and dehydroevodiamine with a view towards their potential use as treatments for AD.

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“…MD simulation is a technique for the calculation of “movement” of the complex. Several previous studies have revealed the problem that some well-docked ligand might “fly” away from the binding pocket in MD simulation [42]. In this study, we use MD simulation as an essential validation before we draw conclusions from docking results.…”

Section: Discussionmentioning

confidence: 99%

Osimertinib (AZD9291), a Mutant-Selective EGFR Inhibitor, Reverses ABCB1-Mediated Drug Resistance in Cancer Cells

Zhang

Wang

et al. 2016

Molecules

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Abstract:In recent years, tyrosine kinase inhibitors (TKIs) have been shown capable of inhibiting the ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR). In this study, we determine whether osimertinib, a novel selective, irreversible EGFR (epidermal growth factor receptor) TKI, could reverse ABC transporter-mediated MDR. The results showed that, at non-toxic concentrations, osimertinib significantly sensitized both ABCB1-transfected and drug-selected cell lines to substrate anticancer drugs colchicine, paclitaxel, and vincristine. Osimertinib significantly increased the accumulation of [ 3 H]-paclitaxel in ABCB1 overexpressing cells by blocking the efflux function of ABCB1 transporter. In contrast, no significant alteration in the expression levels and localization pattern of ABCB1 was observed when ABCB1 overexpressing cells were exposed to 0.3 µM osimertinib for 72 h. In addition, ATPase assay showed osimertinib stimulated ABCB1 ATPase activity. Molecular docking and molecular dynamic simulations showed osimertinib has strong and stable interactions at the transmembrane domain of human homology ABCB1. Taken together, our findings suggest that osimertinib, a clinically-approved third-generation EGFR TKI, can reverse ABCB1-mediated MDR, which supports the combination therapy with osimertinib and ABCB1 substrates may potentially be a novel therapeutic stategy in ABCB1-positive drug resistant cancers.

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Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer

Cited by 5 publications

References 46 publications

Discovery of potential SARS-CoV 3CL protease inhibitors from approved antiviral drugs using: virtual screening, molecular docking, pharmacophore mapping evaluation and dynamics simulation

Discovery of potential SARS-CoV 3CL protease inhibitors from approved antiviral drugs using: virtual screening, molecular docking, pharmacophore mapping evaluation and dynamics simulation

Biocomputational Screening of Natural Compounds against Acetylcholinesterase

Osimertinib (AZD9291), a Mutant-Selective EGFR Inhibitor, Reverses ABCB1-Mediated Drug Resistance in Cancer Cells

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