Application of the SwissDrugDesign Online Resources in Virtual Screening

Daina, Antoine; Zoete, Vincent

doi:10.3390/ijms20184612

Cited by 73 publications

(53 citation statements)

References 73 publications

(100 reference statements)

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“…Drugability assessment was performed with the use of SwissADME software powered by ChemAxon [ 52 , 53 ]. At first, step mol files were translated into Simplified Molecular Input Line Entry Specification by Marvin JS [ 54 ].…”

Section: Methodsmentioning

confidence: 99%

Selective Cytotoxicity of Complexes with N,N,N-Donor Dipodal Ligand in Tumor Cells

Tyszka-Czochara

Adach

Grabowski

et al. 2021

IJMS

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The present article demonstrates selective cytotoxicity against cancer cells of the complexes [Co(LD)2]I2∙CH3OH (1), [CoLD(NCS)2] (2) and [VOLD(NCS)2]∙C6H5CH3 (3) containing the dipodal tridentate ligand LD = N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)amine), formed in situ. All tested complexes expressed greater anticancer activities and were less toxic towards noncancerous cells than cisplatin. Cobalt complexes (1 and 2) combined high cytotoxicity with selectivity towards cancer cells and caused massive tumour cell death. The vanadium complex (3) induced apoptosis specifically in cancer cells and targeted proteins, controlling their invasive and metastatic properties. The presented experimental data and computational prediction of drug ability of coordination compounds may be helpful for designing novel and less toxic metal-based anticancer species with high specificities towards tumour cells.

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Section: Methodsmentioning

confidence: 99%

Selective Cytotoxicity of Complexes with N,N,N-Donor Dipodal Ligand in Tumor Cells

Tyszka-Czochara

Adach

Grabowski

et al. 2021

IJMS

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“…1 The chemical components that meet both of the requirements OB ≥ 30%, DL ≥ 0.18, were retained as candidate active ingredients ( Tao et al, 2013 ). The targets of candidate active ingredients were obtained from Swiss Target Prediction 2 ( Daina and Zoete, 2019 ). Species were selected as “Homo sapiens” and the targets with probability greater than 0 were predicted as the putative targets.…”

Section: Methodsmentioning

confidence: 99%

An Integrative Pharmacology-Based Pattern to Uncover the Pharmacological Mechanism of Ginsenoside H Dripping Pills in the Treatment of Depression

et al. 2021

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Objectives: To evaluate the pharmacodynamical effects and pharmacological mechanism of Ginsenoside H dripping pills (GH) in chronic unpredictable mild stress (CUMS) model rats.Methods: First, the CUMS-induced rat model was established to assess the anti-depressant effects of GH (28, 56, and 112 mg/kg) by the changes of the behavioral indexes (sucrose preference, crossing score, rearing score) and biochemical indexes (serotonin, dopamine, norepinephrine) in Hippocampus. Then, the components of GH were identified by ultra-performance liquid chromatography-iron trap-time of flight-mass spectrometry (UPLC/IT-TOF MS). After network pharmacology analysis, the active ingredients of GH were further screened out based on OB and DL, and the PPI network of putative targets of active ingredients of GH and depression candidate targets was established based on STRING database. The PPI network was analyzed topologically to obtain key targets, so as to predict the potential pharmacological mechanism of GH acting on depression. Finally, some major target proteins involved in the predictive signaling pathway were validated experimentally.Results: The establishment of CUMS depression model was successful and GH has antidepressant effects, and the middle dose of GH (56 mg/kg) showed the best inhibitory effects on rats with depressant-like behavior induced by CUMS. Twenty-eight chemical components of GH were identified by UPLC/IT-TOF MS. Subsequently, 20(S)-ginsenoside Rh2 was selected as active ingredient and the PPI network of the 43 putative targets of 20(S)-ginsenoside Rh2 containing in GH and the 230 depression candidate targets, was established based on STRING database, and 47 major targets were extracted. Further network pharmacological analysis indicated that the cAMP signaling pathway may be potential pharmacological mechanism regulated by GH acting on depression. Among the cAMP signaling pathway, the major target proteins, namely, cAMP, PKA, CREB, p-CREB, BDNF, were used to verify in the CUMS model rats. The results showed that GH could activate the cAMP-PKA-CREB-BDNF signaling pathway to exert antidepressant effects.Conclusions: An integrative pharmacology-based pattern was used to uncover that GH could increase the contents of DA, NE and 5-HT, activate cAMP-PKA-CREB-BDNF signaling pathway exert antidepressant effects.

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“…In the present study, the putative molecular targets of the cathine, cathinone, and both cathedulins were obtained using SwissTargetPrediction ( http://www.swisstargetprediction.ch/ ) ( Gfeller et al, 2014 ) ( Supplementary Figure S1 ). Canonical and isomeric SMILES of cathine, cathinone, catheduline K2, and catheduline E5 were used as input sequences in the SwissTargetPrediction webserver to virtually screen the molecular targets ( Daina and Zoete, 2019 ). The SwissTargetPrediction virtual screening tool uses the "similarity principle" to predict the most probable targets of bioactive molecules such as cathine, cathinone, catheduline K2, and catheduline E5 ( Gfeller et al, 2013 ; Gfeller et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

“…The SwissTargetPrediction virtual screening tool uses the "similarity principle" to predict the most probable targets of bioactive molecules such as cathine, cathinone, catheduline K2, and catheduline E5 ( Gfeller et al, 2013 ; Gfeller et al, 2014 ). In this virtual reverse screening tool, the putative binding predictions are accomplished from 376,342 experimentally active analogous compounds in 2D and 3D that strongly interact with 3,068 well-recognized protein targets ( Huang et al, 2018 ; Daina and Zoete, 2019 ) . In the latest version of the SwissTargetPrediction, the dataset is based on ChEMBL23, and putative protein targets are ranked based on a score that merges both 2D and 3D similarity values of an active molecule to the query molecules such as cathine, cathinone, catheduline K2, and catheduline E5 ( Daina et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Unraveling the Catha edulis Extract Effects on the Cellular and Molecular Signaling in SKOV3 Cells

et al. 2021

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Khat (Catha edulis (Vahl) Endl.) is an evergreen flowering shrub used as a stimulant in many regions worldwide including East Africa, the Arabian Peninsula, Europe, and the United States. Chewing leaves of khat induces excitement and euphoria, which are primarily attributed to two major constituents, cathinone and cathine. Khat also contains other important constituents such as cathedulins. A considerable number of studies reported side effects induced by the khat extracts to both embryos and adults. These include teratogenicity and developmental retardation, oral cancer and ulcers, high blood pressure, and myocardial infarction. So far, little attention has been paid to the effects of khat extracts on the molecular signaling interactions. We aimed in this study to investigate this through evaluating the effects of khat extracts on SKOV3, a human ovarian adenocarcinoma cell line. We show, by in vitro assays, that khat induces several cellular defects including reduced cell size, cell membrane damage, and apoptosis. At high khat extract concentrations, the cell metabolic activity, cell cycle, and cellular proliferation were affected. RT-qPCR analysis showed an increase in the gene expression of the apoptotic marker BAX, the tumor suppressor p53, and the inflammatory cytokine IL-6. Protein expression analysis by immunostaining showed downregulation of β-catenin, E-cadherin, and Ki-67 and upregulation of FZD8 and SPRY2, suggesting that Wnt and FGF signaling were implicated. SwissTargetPrediction in silico analysis showed that khat constituents cathine, cathinone, catheduline K2, and catheduline E5 bind to family A G-protein-coupled receptor, cause many neurological diseases and disorders such as Alzheimer's, schizophrenia, depression, and anxiety, and induce many ovarian cancer-related diseases. The analysis also showed that important signaling pathways such as CREB, Wnt, FGF, IL-6, and ERK/MAPK, and that of the endometrial cancer, and cell cycle were implicated. Upstream regulators of cathine and cathinone were found to potentially target several molecules including interleukin-8, MMP2, PLAU, and micro-RNAs. In conclusion, khat induces significant cellular and molecular changes that could potentially cause a wide range of serious diseases and syndromes. Such an impact could have a heavy burden on the health care system in the countries where khat is consumed.

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Application of the SwissDrugDesign Online Resources in Virtual Screening

Cited by 73 publications

References 73 publications

Selective Cytotoxicity of Complexes with N,N,N-Donor Dipodal Ligand in Tumor Cells

Selective Cytotoxicity of Complexes with N,N,N-Donor Dipodal Ligand in Tumor Cells

An Integrative Pharmacology-Based Pattern to Uncover the Pharmacological Mechanism of Ginsenoside H Dripping Pills in the Treatment of Depression

Unraveling the Catha edulis Extract Effects on the Cellular and Molecular Signaling in SKOV3 Cells

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