Strategies for improving the solubility and metabolic stability of griseofulvin analogues
| Autor: | Mads Hartvig Clausen, Alwin Krämer, Marc S. Raab, Nur Hafzan Md Hanafiah, Asger B. Petersen, Peter Hammershøj, Gleb Konotop |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Ketone Antineoplastic Agents 010402 general chemistry Antifungal 01 natural sciences Griseofulvin Mice Structure-Activity Relationship chemistry.chemical_compound Synthesis Drug Stability SDG 3 - Good Health and Well-being Microsomes Drug Discovery Animals Humans Organic chemistry Structure–activity relationship Solubility Pharmacology chemistry.chemical_classification Griseofulvin analogues Natural product 010405 organic chemistry Aryl Organic Chemistry General Medicine Metabolic stability Rats 0104 chemical sciences Anticancer chemistry Thermodynamics Cancer cell lines Oxidation-Reduction HeLa Cells |
| Zdroj: | Petersen, A B, Konotop, G, Hanafiah, N H M, Hammershøj, P, Raab, M S, Kraemer, A & Clausen, M H 2016, ' Strategies for improving the solubility and metabolic stability of griseofulvin analogues ', European Journal of Medicinal Chemistry, vol. 116, pp. 210-215 . https://doi.org/10.1016/j.ejmech.2016.03.071 |
| DOI: | 10.1016/j.ejmech.2016.03.071 |
| Popis: | We report two types of modifications to the natural product griseofulvin as strategies to improve solubility and metabolic stability: the conversion of aryl methyl ethers into aryl difluoromethyl ethers at metabolic hotspots and the conversion of the C-ring ketone into polar oximes. The syntheses of the analogues are described together with their solubility, metabolic half-life in vitro and antiproliferative effect in two cancer cell lines. We conclude that on balance, the formation of polar oximes is the most promising strategy for improving the properties of the analogues. |
| Databáze: | OpenAIRE |
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