Synthesis, physicochemical properties and biological activities of novel alkylphosphocholines with foscarnet moiety
| Autor: | Ján Mojžiš, Mária Garajová, Anna Juhásová, Lukáš Timko, Martin Pisárčik, Marián Bukovský, Ferdinand Devínsky, Martin Mrva, Miloš Lukáč, Gabriela Mojžišová |
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| Rok vydání: | 2020 |
| Předmět: |
Antifungal Agents
Phosphorylcholine Acanthamoeba Antineoplastic Agents Microbial Sensitivity Tests 01 natural sciences Biochemistry Micelle Mice Structure-Activity Relationship Parasitic Sensitivity Tests Pulmonary surfactant Candida albicans Drug Discovery Amphiphile Animals Humans Surface Tension Moiety Amebicides Molecular Biology Cells Cultured Micelles Alkyl Cell Proliferation chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Biological activity 3T3 Cells Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Critical micelle concentration Lipophilicity Hydrodynamics Drug Screening Assays Antitumor Foscarnet |
| Zdroj: | Bioorganic Chemistry. 104:104224 |
| ISSN: | 0045-2068 |
| Popis: | A series of alkylphosphocholines with foscarnet moiety was synthesized. The structure of these zwitterionic amphiphiles was modified in both polar and non-polar parts of surfactant molecule. Investigations of physicochemical properties are represented by the determination of critical micelle concentration, the surface tension value at the cmc and the surface area per surfactant head group utilising surface tension measurements. Hydrodynamic diameter of surfactant micelles was determined using the dynamic light scattering technique. Alkylphosphocholines exhibit significant cytotoxic, anticandidal (Candida albicans) and antiamoebal (Acanthamoeba spp. T4 genotype) activity. The relationship between the structure, physicochemical properties and biological activity of the tested compounds revealed that lipophilicity has a significant influence on biological activity of the investigated surfactants. More lipophilic alkylphosphocholines with octadecyl chains show cytotoxic activity against cancer cells which is higher than that of the compounds with shorter alkyl chains. The opposite situation was observed in case of anticandidal and antiamoebal activity of these surfactants. The most active compounds were found to have pentadecyl chains. The foscarnet analogue of miltefosine C15-PFA-C showed the highest anticandidal activity. The minimum value of anticandidal activity of this compound is 1,4 μM thus representing the highest anticandidal activity found within the group of alkylphosphocholines. |
| Databáze: | OpenAIRE |
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