<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Naproxen, as a propionic acid derivative, causes serious gastrointestinal side effects due to the presence of free carboxylic group. In that sense, masking of carboxylic group with other pharmacophores may be a promising strategy to decrease gastrointestinal toxicity. Thiourea derivatives have been intensively investigated as potential antitumor drugs, whereby their activity is based on potential inhibition of protein kinases, topoisomerases, carbonic anhydrase and sirtuins. In addition, it was shown that inhibition of certain protein kinases might reverse resistance to chemotherapeutic drugs by enhancing the cell death in the presence of low concentrations of drug. Twenty new thiourea derivatives of naproxen were designed and their binding to four selected protein kinases involved in tumor multidrug resistance (AKT2, mTOR, EGFR and VEGFR1) was estimated using two molecular docking programs (AutoDock Vina and OEDocking). According to OEDocking, the highest potential to inhibit AKT2 and mTor has derivative 1, while derivative 20 demonstrates the highest potential towards EGFR and VEGFR1. According to AutoDock Vina, the highest potential for inhibition of EGFR, AKT2 and VEGFR1 have derivatives 16 and 17. Therefore, derivatives 1, 16, 17 and 20 are potentially the most potent protein kinase inhibitors that could be further synthesized and tested for anticancer activity.</p>
</abstract>

Naproxen, as a propionic acid derivative, causes serious gastrointestinal side effects due to the presence of free carboxylic group. In that sense, masking of carboxylic group with other pharmacophores may be a promising strategy to decrease gastrointestinal toxicity. Thiourea derivatives have been intensively investigated as potential antitumor drugs, whereby their activity is based on potential inhibition of protein kinases, topoisomerases, carbonic anhydrase and sirtuins. In addition, it was shown that inhibition of certain protein kinases might reverse resistance to chemotherapeutic drugs by enhancing the cell death in the presence of low concentrations of drug. Twenty new thiourea derivatives of naproxen were designed and their binding to four selected protein kinases involved in tumor multidrug resistance (AKT2, mTOR, EGFR and VEGFR1) was estimated using two molecular docking programs (AutoDock Vina and OEDocking). According to OEDocking, the highest potential to inhibit AKT2 and mTor has derivative 1, while derivative 20 demonstrates the highest potential towards EGFR and VEGFR1. According to AutoDock Vina, the highest potential for inhibition of EGFR, AKT2 and VEGFR1 have derivatives 16 and 17. Therefore, derivatives 1, 16, 17 and 20 are potentially the most potent protein kinase inhibitors that could be further synthesized and tested for anticancer activity.

Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity

Faculty of Medical Sciences, Department of Pharmacy

University of Belgrade – Faculty of Pharmacy

Experimental and Applied Biomedical Research (EABR)

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Naproxen, as a propionic acid derivative, causes serious gastrointestinal side effects due to the presence of free carboxylic group. In that sense, masking of...

Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity

Publié en ligne: 29 sept. 2023

Pages: 235 - 242

Reçu: 17 mai 2021

Accepté: 23 août 2021

DOI: https://doi.org/10.2478/sjecr-2021-0037

Mots clés
Antitumor activity, AutoDock Vina, molecular docking, naproxen, thiourea derivatives

© 2023 Nikola Nedeljkovic et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity

Publié en ligne: 29 sept. 2023

Pages: 235 - 242

Reçu: 17 mai 2021

Accepté: 23 août 2021

DOI: https://doi.org/10.2478/sjecr-2021-0037

Mots clésAntitumor activity, AutoDock Vina, molecular docking, naproxen, thiourea derivatives

© 2023 Nikola Nedeljkovic et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Mots clés
Antitumor activity, AutoDock Vina, molecular docking, naproxen, thiourea derivatives