2. Academic Validation
  3. Synthesis of structural analogues of hexadecylphosphocholine and their antineoplastic, antimicrobial and amoebicidal activity

Synthesis of structural analogues of hexadecylphosphocholine and their antineoplastic, antimicrobial and amoebicidal activity

  • Eur J Med Chem. 2015 Mar 26:93:263-73. doi: 10.1016/j.ejmech.2015.02.014.
Lukáš Timko 1,  Eva Fischer-Fodor 2,  Mária Garajová 3,  Martin Mrva 3,  Gabriela Chereches 2,  František Ondriska 4,  Marián Bukovský 5,  Miloš Lukáč 6,  Janka Karlovská 7,  Janka Kubincová 6,  Ferdinand Devínsky 6
Affiliations

Affiliations

  • 1 Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia. Electronic address: timko@fpharm.uniba.sk.
  • 2 The Oncology Institute "Prof. Dr. Ion Chiricuţă", 400015 Cluj-Napoca, Romania.
  • 3 Department of Zoology, Faculty of Natural Sciences, Comenius University, Mlynská Dolina B-1, 842 15 Bratislava, Slovakia.
  • 4 HPL (Ltd), Department of Parasitology, Microbiological Laboratory, Istrijská 20, 841 07 Bratislava, Slovakia.
  • 5 Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia.
  • 6 Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia.
  • 7 NMR Laboratory, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32 Bratislava, Slovakia; Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia.
PMID: 25698517 DOI: 10.1016/j.ejmech.2015.02.014
Abstract

Twelve derivatives of hexadecylphosphocholine (miltefosine) were synthesized to determine how the position and length of the alkyl chain within the molecule influence their biological activities. The prepared alkylphosphocholines have the same molecular formula as miltefosine. Activity of the compounds was studied against a spectrum of tumour cells, two species of protozoans, bacteria and yeast. Antitumour efficacy of some alkylphosphocholines measured up on MCF-7, A2780, HUT-78 and THP-1 cell lines was higher than that of miltefosine. The compounds showed antiprotozoal activity against Acanthamoeba lugdunensis and Acanthamoeba quina. Some of them also possess fungicidal activity against Candida albicans equal to miltefosine. No Antibacterial activity was observed against Staphylococcus aureus and Escherichia coli. A difference in position of a long hydrocarbon chain within the structure with maximum efficacy was observed for antitumour, antiprotozoal and Antifungal activity.

Keywords

Acanthamoeba; Alkylphosphocholines; Candida albicans; Cut-off effect; Cytotoxic activity; SAR.

Figures