Design, synthesis, anticancer screening, docking studies and in silico ADME prediction of some β-carboline derivatives
| Autor: | Omaima M. Aboulwafa, Mahmoud M. Elaasser, Mai S. El-Shoukrofy, Mohamed A Abdelsalam, El-Sayed A. M. Badawey, Mostafa M.M. El-Miligy, Noha Gouda |
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| Rok vydání: | 2018 |
| Předmět: |
β carboline derivatives
In silico Kinesins Antineoplastic Agents 01 natural sciences 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Catalytic Domain Cell Line Tumor Drug Discovery Humans ADME Cell Proliferation Pharmacology Ligand efficiency Binding Sites 010405 organic chemistry Chemistry Combinatorial chemistry 0104 chemical sciences Molecular Docking Simulation Design synthesis DNA Topoisomerases Type I Docking (molecular) 030220 oncology & carcinogenesis Drug Design Molecular Medicine Drug Screening Assays Antitumor Carbolines Half-Life |
| Zdroj: | Future medicinal chemistry. 10(10) |
| ISSN: | 1756-8927 |
| Popis: | Background: Medicinal interest has focused on β-carbolines as anticancer agents. Methodology/Results: Several β-carbolines were designed, synthesized and evaluated for their cytotoxic activity against MCF-7 and A-549 cancer cell lines using MTT assay. Compounds 13a, 13c, 13d and 20a were the most promising showing high selectivity indices. Compounds 13c and 20a showed potent inhibition of topoisomerase (topo-I) and kinesin spindle protein (KSP/Eg5 ATPase) which was confirmed by their docking results into the active site of both enzymes. In silico physicochemical calculations predicted that compounds 13a, 13d and 20a obeyed Lipinski's rule of five. Conclusion: Compounds 13c and 20a are multitarget anticancer leads that act as potent inhibitors for both topo-I and/or KSP ATPase. |
| Databáze: | OpenAIRE |
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