Affordable Access

deepdyve-link
Publisher Website

Synthesis, physicochemical properties and biological activities of novel alkylphosphocholines with foscarnet moiety.

Authors
  • Timko, Lukáš1
  • Pisárčik, Martin1
  • Mrva, Martin2
  • Garajová, Mária2
  • Juhásová, Anna2
  • Mojžiš, Ján3
  • Mojžišová, Gabriela4
  • Bukovský, Marián5
  • Devínsky, Ferdinand6
  • Lukáč, Miloš7
  • 1 Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia. , (Slovakia)
  • 2 Department of Zoology, Faculty of Natural Sciences, Comenius University, Mlynská Dolina, Ilkovičova 6, 842 15 Bratislava, Slovakia. , (Slovakia)
  • 3 Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, SNP 1, 040 66 Košice, Slovakia. , (Slovakia)
  • 4 Department of Experimental Medicine, Faculty of Medicine, P.J. Šafárik University, SNP 1, 040 66 Košice, Slovakia. , (Slovakia)
  • 5 Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia. , (Slovakia)
  • 6 Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32 Bratislava, Slovakia. , (Slovakia)
  • 7 Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia. Electronic address: [email protected] , (Slovakia)
Type
Published Article
Journal
Bioorganic chemistry
Publication Date
Aug 26, 2020
Volume
104
Pages
104224–104224
Identifiers
DOI: 10.1016/j.bioorg.2020.104224
PMID: 32892068
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2020 Elsevier Inc. All rights reserved.

Report this publication

Statistics

Seen <100 times