Assaying phenothiazine derivatives as trypanothione reductase and glutathione reductase inhibitors by theoretical docking and Molecular Dynamics studies

Iribarne, Federico; Paulino, Margot; Aguilera, Sara; Tapia, O.

doi:10.1016/j.jmgm.2009.09.003

Cited by 21 publications

(14 citation statements)

References 67 publications

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“…The major site of interaction of clomipramine in T. cruzi TryR, clusters 1 and 2, was confirmed to be at the Z-site [19,20], in close proximity to residues Phe396', Pro398', and Leu399' with an H-bond to Glu467'. In the most populated cluster, the tricyclic scaffold lies close to the active CysI-GlyI site [17] with a H-bond to Glu19, as established previously [18,21,22]. Similar binding features were observed with chlorpromazine.…”

supporting

confidence: 78%

Molecular Docking and Binding Mode Analysis of Plant Alkaloids as in Vitro and in silico Inhibitors of Trypanothione Reductase from Trypanosoma cruzi

Argüelles

Cordell

Maruenda

2016

Natural Product Communications

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Trypanothione reductase (TryR) is a key enzyme in the metabolism of Trypanosoma cruzi, the parasite responsible for Chagas disease. The available repertoire of TryR inhibitors relies heavily on synthetic substrates of limited structural diversity, and less on plant-derived natural products. In this study, a molecular docking procedure using a Lamarckian Genetic Algorithm was implemented to examine the protein-ligand binding interactions of strong in vitro inhibitors for which no X-ray data is available. In addition, a small, skeletally diverse, set of natural alkaloids was assessed computationally against T. cruzi TryR in search of new scaffolds for lead development. The preferential binding mode (low number of clusters, high cluster population), together with the deduced binding interactions were used to discriminate among the virtual inhibitors. This study confirms the prior in vitro data and proposes quebrachamine, cephalotaxine, cryptolepine, (22S,25S)-tomatidine, (22R,25S)-solanidine, and (22R,25R)-solasodine as new alkaloid scaffold leads in the search for more potent and selective TryR inhibitors.

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supporting

confidence: 78%

Molecular Docking and Binding Mode Analysis of Plant Alkaloids as in Vitro and in silico Inhibitors of Trypanothione Reductase from Trypanosoma cruzi

Argüelles

Cordell

Maruenda

2016

Natural Product Communications

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“…Owing to its fast and acceptable results, docking became a standard tool in drug design and drug discovery before a more computationally and labor-expensive level of calculation such as molecular dynamics [23][24][25]. When there is a cocrystal of a known drug and target enzyme available, we set up a procedure to predict binding mode, approximate affinity and ranking based on multiple scoring functions of the unknown compounds, as shown in Fig.…”

Section: Virtual Screening Of Active Compounds From Thai Medicinal Plmentioning

confidence: 99%

Computer Techniques for Drug Development from Thai Traditional Medicine

Sangma

Chuakheaw²,

Jonkon³

et al. 2010

CPD

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Thailand has a vast number of plant species. Up to 3000 of them are believed by traditional Thai medicine to possess some biological activity with which researchers have attempted for many years to identify and formulate new drugs. Many chemical compounds from Thai plant species are identified and tested for biological activity that may enable them to be declared lead compounds in drug discovery. Modern methods of drug discovery are rarely used to rationalize and speed-up the process. Within this decade, the first structural database of Thai medicinal plants, Chemiebase, has been built as a platform for virtual screening, using knowledge from Thai traditional medicine. Although this effort is a promising protocol which can be used to validate Thai traditional medicine, there exists another problem that should be resolved before proceeding: It is almost impossible to trace the knowledge to its primary source. Thai traditional knowledge has been passed on orally or - less frequently - in ancient texts. We have built another database, the Thai Herbal Repository Access Initiative (THRAI) database, in order to compile the traditional knowledge into electronic format suitable for the drug design process. Three examples using data from these databases and other computer-aided drug discovery methods to rationalize Thai traditional medicine are presented here, starting with virtual screening exercised on anti-HIV-1 reverse transcriptase, anti-HIV-1 protease, anti-influenza A neuraminidase, and anti-cyclooxygenase (COX), candidates. The second example consists of the use of molecular modeling to propose drug mechanism for anti-tumor compounds. The last one is the study on toxicity assessment of some compounds from Thai medicinal plants.

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“…Glutathione reductase-targeting compounds are approved of new candidates as antimalarial and anticancer drugs [34,35]. We have recently reported that antimony(III) compounds exhibit good glutathione reductase inhibitory activities [36,37].…”

Section: Introductionmentioning

confidence: 99%

Antimony(III) complexes with 2-amino-4,6-dimethoxypyrimidines: Synthesis, characterization and biological evaluation

Tunç

Karacan

Ertabaklar

et al. 2015

Journal of Photochemistry and Photobiology B: Biology

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Assaying phenothiazine derivatives as trypanothione reductase and glutathione reductase inhibitors by theoretical docking and Molecular Dynamics studies

Cited by 21 publications

References 67 publications

Molecular Docking and Binding Mode Analysis of Plant Alkaloids as in Vitro and in silico Inhibitors of Trypanothione Reductase from Trypanosoma cruzi

Molecular Docking and Binding Mode Analysis of Plant Alkaloids as in Vitro and in silico Inhibitors of Trypanothione Reductase from Trypanosoma cruzi

Computer Techniques for Drug Development from Thai Traditional Medicine

Antimony(III) complexes with 2-amino-4,6-dimethoxypyrimidines: Synthesis, characterization and biological evaluation

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