Rational Design, Synthesis and Cytotoxic Activity of N-(Phenylcarbamoyl)Benzamide on HeLa Cell Lines
| Autor: | Bambang Tri Purwanto, Siswandono Siswandono, Suko Hardjono, Dian Triwidiandany |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Journal of Mathematical and Fundamental Sciences, Vol 52, Iss 2 (2020) |
| Druh dokumentu: | article |
| ISSN: | 2337-5760 2338-5510 |
| DOI: | 10.5614/j.math.fund.sci.2020.52.2.3 |
| Popis: | Urea derivatives are extensively used in the pharmaceutical industry. However, the unsatisfactory level of their membrane penetration requires further modification of the structures with stronger lipophillic properties. Phenylurea has a phenyl group that enables easier membrane penetration as a result of stronger pharmacological activity. Activity prediction was conducted by docking experiments and molecular dynamics, performed with Molegro Virtual Docker 5.5 using checkpoint kinase 1 (CHK1) enzyme with ID PDB: 2YWP. ADMET prediction was applied to collect data using the pkCSM tool. N-(phenyl carbamyol)benzamide compounds, modified by the Schotten Baumann method, were synthesized from benzoil chloride reacting with N-phenylurea. For evaluating anticancer activity, the MTT assay method on HeLa cells was used. Derived from the docking experiments, the compound rerank score of the N-(phenylcarbamoyl)benzamide was 72.0603 kcal/mol, lower than that of hydroxyurea, -32.1514 kcal/mol, causing better inhibitory activities against HeLA cell lines due to higher cytotoxic effects. ADMET Predictor was employed, indicating satisfactory compound distribution with a low, favorable metabolism, possessing good excretion and non-toxicity. The synthesized compound was 82% N-(phenyl carbamoyl)benzamide with 0.8 mM IC80, higher than that of hydroxyurea, 4.3 mM. In conclusion, successfully synthesized N-(phenylcarbamoyl)benzamide was proved to have higher cytotoxic effects. The satisfactory values of these compounds indicate that they are promising anticancer drug candidates. |
| Databáze: | Directory of Open Access Journals |
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