<i>In silico</i>screening-based discovery of inhibitors against glycosylation proteins dysregulated in cancer

Alvarez, Michael Russelle; Grijaldo, Sheryl Joyce; Nacario, Ruel C.; Rabajante, Jomar F.; Heralde, Francisco M.; Lebrilla, Carlito B.; Completo, Gladys C.

doi:10.1080/07391102.2021.2022534

Cited by 7 publications

(12 citation statements)

References 62 publications

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“…The compounds from LH6‐6 and LH7‐6 identified through GC‐MS analysis were predicted to have protein interactions based on network pharmacolog analysis using Chemical Toxicogenomics Database (http://ctdbase.org/). 14 The network was then visualized using Cytoscape software complexed with STRING database (http://apps.cytoscape.org/apps/stringapp) to provide the compound‐protein networks with functional associations from curated pathways, automatic text mining, and prediction methods 15,16 …”

Section: Methodsmentioning

confidence: 99%

“…14 The network was then visualized using Cytoscape software complexed with STRING database (http:// apps.cytoscape.org/apps/stringapp) to provide the compoundprotein networks with functional associations from curated pathways, automatic text mining, and prediction methods. 15,16 3 | RESULTS AND DISCUSSION 3.1 | Bioassay-guided purification and GC-MS characterization of L. domesticum fractions L. domesticum leaves were extracted with hexane to obtain the crude extract. The extract was purified using normal phase column chromatography under the guidance of cytotoxicity assay (MTS assay) to identify two bioactive fractions with high cytotoxicity against lung cancer cells (A549) (Figure 1).…”

Section: Network Pharmacology Of Predicted Compound-protein Interactionsmentioning

confidence: 99%

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Comparative proteomics reveals anticancer compounds from Lansium domesticum against NSCLC cells target mitochondrial processes

Alvarez

Juan

Zhou

et al. 2023

Cell Biochemistry & Function

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Lansium domesticum is identified as a potential source of anticancer compounds. However, there are minimal studies on its anti-lung cancer properties as well as its mechanism of action. Here, we show the specificity of lanzones hexane (LH) leaf extracts to non-small cell lung cancer cells (A549) compared to normal lung fibroblast cells (CCD19-Lu) and normal epithelial prostate cells (PNT2). Subsequent bioassay-guided fractionation of the hexane leaf extracts identified two bioactive fractions with IC 50 values of 2.694 μg/ml (LH6-6) and 2.883 μg/ml (LH7-6). LH 6-6 treatment (1 μg/ml concentration) also showed a significantly reduced migration potential of A549 relative to the control. Thirty-one phytocompounds were isolated and identified using gas chromatography-mass spectrometric (MS) analysis and were then subjected to network pharmacology analysis to assess its effects on lung cancer target proteins. Using liquid chromatography-tandem mass spectrometry proteomics experiments, we were able to show that these compounds cause cytotoxic effects through targeting mitochondrial processes in A549 lung cancer cells.

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Section: Methodsmentioning

confidence: 99%

Section: Network Pharmacology Of Predicted Compound-protein Interactionsmentioning

confidence: 99%

Comparative proteomics reveals anticancer compounds from Lansium domesticum against NSCLC cells target mitochondrial processes

Alvarez

Juan

Zhou

et al. 2023

Cell Biochemistry & Function

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“…17−22 Our previous study also employed an in silico method as a preliminary tool to screen 14,000 small molecule inhibitors against glycosylation proteins dysregulated in cancer. 17 In this study, we incorporated computational methods in network pharmacology and in silico docking approaches to predict phytochemical compounds that could potentially interact with several cancer-associated glycoproteins and glycosylation-related proteins. We inferred that the cytotoxicity of select phytochemicals against cancer cells could reveal the effects of these compounds against aberrant glycosylation, and their potential as drug leads in anti-lung cancer drug discovery.…”

Section: ■ Introductionmentioning

confidence: 99%

“…to discover, among the ENAMINE compounds database, 7,8-diaminopelargonic acid aminotransferase inhibitors that could inhibit the growth of Mycobacterium tuberculosis strain Mtb H37Ra . During the recent pandemic, the use of in silico methods is one of the drug discovery approaches utilized to address an urgent need to find new drugs against COVID-19 and other diseases like HIV-AIDS and cancer. − Our previous study also employed an in silico method as a preliminary tool to screen 14,000 small molecule inhibitors against glycosylation proteins dysregulated in cancer …”

Section: Introductionmentioning

confidence: 99%

“… 11 During the recent pandemic, the use of in silico methods is one of the drug discovery approaches utilized to address an urgent need to find new drugs against COVID-19 and other diseases like HIV-AIDS and cancer. 12 − 53 Our previous study also employed an in silico method as a preliminary tool to screen 14,000 small molecule inhibitors against glycosylation proteins dysregulated in cancer. 12 …”

Section: Introductionmentioning

confidence: 99%

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Integrating Computational Methods in Network Pharmacology and In Silico Screening to Uncover Multi-targeting Phytochemicals against Aberrant Protein Glycosylation in Lung Cancer

et al. 2023

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Glycoproteins are an underexploited drug target for cancer therapeutics. In this work, we integrated computational methods in network pharmacology and in silico docking approaches to identify phytochemical compounds that could potentially interact with several cancer-associated glycoproteins. We first created a database of phytochemicals from selected plant species, Manilkara zapota (sapodilla/chico), Mangifera indica (mango), Annona muricata (soursop/guyabano), Artocarpus heterophyllus (jackfruit/langka), Lansium domesticum (langsat/lanzones), and Antidesma bunius (bignay), and performed pharmacokinetic analysis to determine their drug-likeness properties. We then constructed a phytochemical–glycoprotein interaction network and characterized the degree of interactions between the phytochemical compounds and with cancer-associated glycoproteins and other glycosylation-related proteins. We found a high degree of interactions from α-pinene (Mangifera indica), cyanomaclurin (Artocarpus heterophyllus), genistein (Annona muricata), kaempferol (Annona muricata and Antidesma bunius), norartocarpetin (Artocarpus heterophyllus), quercetin (Annona muricata, Antidesma bunius, Manilkara zapota, Mangifera indica), rutin (Annona muricata, Antidesma bunius, Lansium domesticum), and ellagic acid (Antidesma bunius and Mangifera indica). Subsequent docking analysis confirmed that these compounds could potentially bind to EGFR, AKT1, KDR, MMP2, MMP9, ERBB2, IGF1R, MTOR, and HRAS proteins, which are known cancer biomarkers. In vitro cytotoxicity assays of the plant extracts showed that the n-hexane, ethyl acetate, and methanol leaf extracts from A. muricata, L. domesticum and M. indica gave the highest growth inhibitory activity against A549 lung cancer cells. These may help further explain the reported cytotoxic activities of select compounds from these plant species.

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Untargeted metabolomics‐based identification of bioactive compounds from Mangifera indica L. seed extracts in drug discovery through molecular docking and assessment of their anticancer potential

Kaneria,

Rakholiya,

Bavaliya

et al. 2024

J Sci Food Agric

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BackgroundMangifera indica L. (mango), a medicinal plant rich in biologically active compounds have potential to be used in disease‐preventing and health‐promoting products. The present investigation reveals and uncovers bioactive metabolites with remarkable therapeutic efficiency from mango (Family: Anacardiaceae) seeds.ResultsBiological activity was determined by antimicrobial, antioxidant, and anticancer assays, and metabolite profiling was performed on the gas chromatography coupled to quadrupole time‐of‐flight mass spectrometry (GC‐QTOF‐MS) and liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS) platforms. Validation of active metabolites was carried out by in silico molecular docking (Molinspiration Cheminformatics Server and PASS). Extracted and identified metabolites were screened; 54 compounds associated with various groups were selected for the in silico interaction study.ConclusionsMolecular docking revealed lead molecules with a potential binding energy score, its efficacy and stable modulation with a selected protein domain. Investigation, directed by in vitro and in silico analysis, confirms mango seeds as an excellent source of potential metabolites as a therapeutic agent.This article is protected by copyright. All rights reserved.

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In silicoscreening-based discovery of inhibitors against glycosylation proteins dysregulated in cancer

Cited by 7 publications

References 62 publications

Comparative proteomics reveals anticancer compounds from Lansium domesticum against NSCLC cells target mitochondrial processes

Comparative proteomics reveals anticancer compounds from Lansium domesticum against NSCLC cells target mitochondrial processes

Integrating Computational Methods in Network Pharmacology and In Silico Screening to Uncover Multi-targeting Phytochemicals against Aberrant Protein Glycosylation in Lung Cancer

Untargeted metabolomics‐based identification of bioactive compounds from Mangifera indica L. seed extracts in drug discovery through molecular docking and assessment of their anticancer potential

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