A computational molecular docking study of camptothecin similars as inhibitors for topoisomerase 1

Boudjedir, Atidel; Kraim, Khaireddine; Saihi, Youcef; Attoui-Yahia, Ouassila; Ferkous, Fouad; Nacereddine, Abdelmalek Khorief

doi:10.1007/s11224-020-01633-6

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…The discovery and development of antitumor drugs from natural products, especially from plants, is currently a research hotspot [ 4 , 5 , 6 ]. For instance, camptothecin (CPT), isolated from the Chinese tree Camptotheca acuminnata , is a specific inhibitor of DNA topoisomerase 1 (DNA-TOP1), which is an important anticancer target [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Evodiamine and Rutaecarpine as Potential Anticancer Compounds: A Combined Computational Study

Liu¹,

Guo²,

Zhou³

et al. 2022

IJMS

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Evodiamine (EVO) and rutaecarpine (RUT) are the main active compounds of the traditional Chinese medicinal herb Evodia rutaecarpa. Here, we fully optimized the molecular geometries of EVO and RUT at the B3LYP/6-311++G (d, p) level of density functional theory. The natural population analysis (NPA) charges, frontier molecular orbitals, molecular electrostatic potentials, and the chemical reactivity descriptors for EVO and RUT were also investigated. Furthermore, molecular docking, molecular dynamics simulations, and the analysis of the binding free energies of EVO and RUT were carried out against the anticancer target topoisomerase 1 (TOP1) to clarify their anticancer mechanisms. The docking results indicated that they could inhibit TOP1 by intercalating into the cleaved DNA-binding site to form a TOP1–DNA–ligand ternary complex, suggesting that they may be potential TOP1 inhibitors. Molecular dynamics (MD) simulations evaluated the binding stability of the TOP1–DNA–ligand ternary complex. The calculation of binding free energy showed that the binding ability of EVO with TOP1 was stronger than that of RUT. These results elucidated the structure–activity relationship and the antitumor mechanism of EVO and RUT at the molecular level. It is suggested that EVO and RUT may be potential compounds for the development of new anticancer drugs.

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Section: Introductionmentioning

confidence: 99%

Evodiamine and Rutaecarpine as Potential Anticancer Compounds: A Combined Computational Study

Liu¹,

Guo²,

Zhou³

et al. 2022

IJMS

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“…Moreover, 16 shared the positive control (irinotecan) the presence of three interactions with (Glu 356, Asp 533, and Lys 532) topoisomerase-1 residues ( Table S4 , Figure 6 ), which represent essential residues for activity [ 47 , 48 ]. However, irinotecan has a higher activity due to the presence of another interaction with the active residue (Thr 718) in addition to numerous H-bond and Van der Waals interactions with DNA basis and other active enzyme residues.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Promising Cytotoxic Metabolites from Tabebuia guayacan Hemsl.: Computational Prediction and In Vitro Testing

El‐Hawary

Mohammed

Taher

et al. 2022

Plants

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Genus Tabebuia is famous for its traditional uses and valuable phytoconstituents. Our previous investigation of Tabebuia species noted the promising anticancer activity of T. guayacan Hemsl. leaves extract, however, the mechanism underlying the observed anticancer activity is still unexplored. The current research was designed to explore the phytochemical content as well as to address the phytoconstituent(s) responsible for the recorded anticancer activity. Accordingly, sixteen compounds were isolated, and their structures were elucidated using different spectroscopic techniques. The drug-likeness of the isolated compounds, as well as their binding affinity with four anticancer drug target receptors: CDK-2/6, topoisomerase-1, and VEGFR-2, were evaluated. Additionally, the most promising compounds were in vitro evaluated for inhibitory activities against CDK-2/6 and VEGFR-2 enzymes using kinase assays method. Corosolic acid (3) and luteolin-7-O-β-glucoside (16) were the most active inhibitors against CDK-2 (−13.44 kcal/mol) and topoisomerase 1 (−13.83 kcal/mol), respectively. Meanwhile, quercetin 3-O-β-xyloside (10) scored the highest binding free energies against both CDK-6 (−16.23 kcal/mol) as well as against VEGFR-2 protein targets (−10.39 kcal/mol). Molecular dynamic simulation indicated that quercetin 3-O-β-xyloside (10) exhibited the least fluctuations and deviations from the starting binding pose with RMSD (2.6 Å). Interestingly, in vitro testing results confirmed the potent activity of 10 (IC50 = 0.154 µg/mL) compared to IC50 = 0.159 µg/mL of the reference drug ribociclib. These findings suggest the three noted compounds (3, 10, and 16) for further in vivo anticancer studies.

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“…Before declaring these molecules as hits, we have decided to do molecular dynamics simulation as the nal step in order to con rm the molecular docking results [50].…”

Section: Molecular Dockingmentioning

confidence: 99%

Virtual screening, XGBoost based QSAR modelling, Molecular Docking and Molecular Dynamics Simulation approach to discover a new inhibitor targeting ErbB1 Protein

Bouchama,

Kraim,

Brahimi

et al. 2024

Preprint

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ErbB1 is a protein found on certain types of human cells that binds to a substance called epidermal growth factor (EGFR). The ErbB1 protein is involved in cell signalling pathways that control cell division, proliferation, and survival. Sometimes, mutations in the EGFR gene cause ErbB1 proteins to be made in higher-than-normal amounts on some types of cancer cells. The aim of this study is using the virtual screening based on ligand and structure drug design using respectively QSAR, molecular docking & molecular dynamics simulations approaches to identify novel antitumor small molecules. Therefore, the QSAR model was developed and validated using XGBOOST as a learning algorithm classifier trained on 5215 compounds. The validated model is used for screening of more than 80k natural products downloaded and prepared from the ZINC database to offer us only 36 as potent predicted inhibitors against ErbB1. The selected active compounds were docked against the target represented by the PDB ID: 3POZ. The obtained top five scoring compounds were compared to the reference ligand TAK285, to the Lapatinib and the Erlotinib drugs, after this phase their stability into the ErbB1 protein binding site has been validated using the molecular dynamics simulation.

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A computational molecular docking study of camptothecin similars as inhibitors for topoisomerase 1

Cited by 6 publications

References 30 publications

Evodiamine and Rutaecarpine as Potential Anticancer Compounds: A Combined Computational Study

Evodiamine and Rutaecarpine as Potential Anticancer Compounds: A Combined Computational Study

Characterization of Promising Cytotoxic Metabolites from Tabebuia guayacan Hemsl.: Computational Prediction and In Vitro Testing

Virtual screening, XGBoost based QSAR modelling, Molecular Docking and Molecular Dynamics Simulation approach to discover a new inhibitor targeting ErbB1 Protein

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