Evaluation of N-benzoylthiourea derivatives as possible analgesic agents by predicting their physicochemical and pharmacokinetic properties, toxicity, and analgesic activity
This study aimed to predict the physicochemical properties, pharmacokinetic properties (ADME), toxicity, and analgesic activity of 30 compounds of N-benzoylthiourea derivatives that are potential analgesic drugs. One of the mechanisms of action of N-benzoylthiourea derivatives is the inhibition of t...
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| Format: | Article |
| Language: | English |
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Universitas Gadjah Mada, Yogyakarta
2018-02-01
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| Series: | Indonesian Journal of Biotechnology |
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| Online Access: | https://jurnal.ugm.ac.id/ijbiotech/article/view/27171 |
| _version_ | 1828417986470346752 |
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| author | Suko Hardjono Siswandono Siswandono Rina Andayani |
| author_facet | Suko Hardjono Siswandono Siswandono Rina Andayani |
| author_sort | Suko Hardjono |
| collection | DOAJ |
| description | This study aimed to predict the physicochemical properties, pharmacokinetic properties (ADME), toxicity, and analgesic activity of 30 compounds of N-benzoylthiourea derivatives that are potential analgesic drugs. One of the mechanisms of action of N-benzoylthiourea derivatives is the inhibition of the cyclooxygenase-2 (COX-2) isoenzyme. An in silico test was performed by docking a compound that would predict its activity with the target COX-2 isoenzyme, PDB ID: 1PXX, using the MVD (Molegro Virtual Docker) program. The result of the docking was a form of energy bond indicated by the value of the rerank score (RS), where compounds that had lower RS values were predicted to have a higher activity. The pkCSM and Protox online tools were used to predict various physicochemical properties. Based on the RS values, the N-benzoylthiourea derivatives can be predicted to have lower analgesic activity than diclofenac, the reference ligand. Three of the N-benzoylthiourea derivatives—N-(2,4-bis-trifluoromethyl)-benzoylthiourea, N-(3,5-bis-trifluoromethyl)benzoylthiourea, and N-(3-trifluoromethoxy)-benzoylthiourea—had RS values of -90.82, -94.73, and -92.76, respectively, suggesting that these compounds were predicted to have analgesic activity relatively similar to diclofenac (RS value = -95.16). Furthermore, the majority of the N-benzoylthiourea derivatives were predicted to have good pharmacokinetic properties (ADME), and cause relatively low toxicity. |
| first_indexed | 2024-12-10T14:29:08Z |
| format | Article |
| id | doaj.art-51ec0e24d1154c918932a92c2070ff52 |
| institution | Directory Open Access Journal |
| issn | 0853-8654 2089-2241 |
| language | English |
| last_indexed | 2024-12-10T14:29:08Z |
| publishDate | 2018-02-01 |
| publisher | Universitas Gadjah Mada, Yogyakarta |
| record_format | Article |
| series | Indonesian Journal of Biotechnology |
| spelling | doaj.art-51ec0e24d1154c918932a92c2070ff522022-12-22T01:44:58ZengUniversitas Gadjah Mada, YogyakartaIndonesian Journal of Biotechnology0853-86542089-22412018-02-01222768510.22146/ijbiotech.2717119167Evaluation of N-benzoylthiourea derivatives as possible analgesic agents by predicting their physicochemical and pharmacokinetic properties, toxicity, and analgesic activitySuko Hardjono0Siswandono Siswandono1Rina Andayani2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Airlangga University, Campus B Jalan Dharmawangsa Dalam, Surabaya 60282, IndonesiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Airlangga University, Campus B Jalan Dharmawangsa Dalam, Surabaya 60282, IndonesiaDepartment of Pharmacy, Faculty of Medicine, Hang Tuah University, Jalan Gadung No. 1, Komplek Barat RSAL dr. Ramelan, Surabaya 60111, IndonesiaThis study aimed to predict the physicochemical properties, pharmacokinetic properties (ADME), toxicity, and analgesic activity of 30 compounds of N-benzoylthiourea derivatives that are potential analgesic drugs. One of the mechanisms of action of N-benzoylthiourea derivatives is the inhibition of the cyclooxygenase-2 (COX-2) isoenzyme. An in silico test was performed by docking a compound that would predict its activity with the target COX-2 isoenzyme, PDB ID: 1PXX, using the MVD (Molegro Virtual Docker) program. The result of the docking was a form of energy bond indicated by the value of the rerank score (RS), where compounds that had lower RS values were predicted to have a higher activity. The pkCSM and Protox online tools were used to predict various physicochemical properties. Based on the RS values, the N-benzoylthiourea derivatives can be predicted to have lower analgesic activity than diclofenac, the reference ligand. Three of the N-benzoylthiourea derivatives—N-(2,4-bis-trifluoromethyl)-benzoylthiourea, N-(3,5-bis-trifluoromethyl)benzoylthiourea, and N-(3-trifluoromethoxy)-benzoylthiourea—had RS values of -90.82, -94.73, and -92.76, respectively, suggesting that these compounds were predicted to have analgesic activity relatively similar to diclofenac (RS value = -95.16). Furthermore, the majority of the N-benzoylthiourea derivatives were predicted to have good pharmacokinetic properties (ADME), and cause relatively low toxicity.https://jurnal.ugm.ac.id/ijbiotech/article/view/27171ADMEanalgesic activitymolecular modelingN-benzoylthioureatoxicity |
| spellingShingle | Suko Hardjono Siswandono Siswandono Rina Andayani Evaluation of N-benzoylthiourea derivatives as possible analgesic agents by predicting their physicochemical and pharmacokinetic properties, toxicity, and analgesic activity Indonesian Journal of Biotechnology ADME analgesic activity molecular modeling N-benzoylthiourea toxicity |
| title | Evaluation of N-benzoylthiourea derivatives as possible analgesic agents by predicting their physicochemical and pharmacokinetic properties, toxicity, and analgesic activity |
| title_full | Evaluation of N-benzoylthiourea derivatives as possible analgesic agents by predicting their physicochemical and pharmacokinetic properties, toxicity, and analgesic activity |
| title_fullStr | Evaluation of N-benzoylthiourea derivatives as possible analgesic agents by predicting their physicochemical and pharmacokinetic properties, toxicity, and analgesic activity |
| title_full_unstemmed | Evaluation of N-benzoylthiourea derivatives as possible analgesic agents by predicting their physicochemical and pharmacokinetic properties, toxicity, and analgesic activity |
| title_short | Evaluation of N-benzoylthiourea derivatives as possible analgesic agents by predicting their physicochemical and pharmacokinetic properties, toxicity, and analgesic activity |
| title_sort | evaluation of n benzoylthiourea derivatives as possible analgesic agents by predicting their physicochemical and pharmacokinetic properties toxicity and analgesic activity |
| topic | ADME analgesic activity molecular modeling N-benzoylthiourea toxicity |
| url | https://jurnal.ugm.ac.id/ijbiotech/article/view/27171 |
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