Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity
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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.
Кључне речи:
Antitumor activity / AutoDock Vina / molecular docking / naproxen / thiourea derivativesИзвор:
Experimental and Applied Biomedical Research (EABR), 2023, 24, 3, 235-242Издавач:
- Sciendo
Институција/група
PharmacyTY - JOUR AU - Nedeljković, Nikola AU - Dobričić, Vladimir AU - Mijajlović, Marina AU - Vujić, Zorica AU - Nikolić, Miloš PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5347 AB - 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. PB - Sciendo T2 - Experimental and Applied Biomedical Research (EABR) T1 - Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity VL - 24 IS - 3 SP - 235 EP - 242 DO - 10.2478/sjecr-2021-0037 ER -
@article{ author = "Nedeljković, Nikola and Dobričić, Vladimir and Mijajlović, Marina and Vujić, Zorica and Nikolić, Miloš", year = "2023", 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.", publisher = "Sciendo", journal = "Experimental and Applied Biomedical Research (EABR)", title = "Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity", volume = "24", number = "3", pages = "235-242", doi = "10.2478/sjecr-2021-0037" }
Nedeljković, N., Dobričić, V., Mijajlović, M., Vujić, Z.,& Nikolić, M.. (2023). Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity. in Experimental and Applied Biomedical Research (EABR) Sciendo., 24(3), 235-242. https://doi.org/10.2478/sjecr-2021-0037
Nedeljković N, Dobričić V, Mijajlović M, Vujić Z, Nikolić M. Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity. in Experimental and Applied Biomedical Research (EABR). 2023;24(3):235-242. doi:10.2478/sjecr-2021-0037 .
Nedeljković, Nikola, Dobričić, Vladimir, Mijajlović, Marina, Vujić, Zorica, Nikolić, Miloš, "Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity" in Experimental and Applied Biomedical Research (EABR), 24, no. 3 (2023):235-242, https://doi.org/10.2478/sjecr-2021-0037 . .