title: Synthesis of structural analogues of hexadecylphosphocholine and their antineoplastic, antimicrobial and amoebicidal activity.
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.
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia. Electronic address: timko@fpharm.uniba.sk.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Timko
authors.affiliation: The Oncology Institute "Prof. Dr. Ion Chiricuţă", 400015 Cluj-Napoca, Romania.
authors.forename: Eva
authors.initials: E
authors.lastname: Fischer-Fodor
authors.affiliation: Department of Zoology, Faculty of Natural Sciences, Comenius University, Mlynská Dolina B-1, 842 15 Bratislava, Slovakia.
authors.forename: Mária
authors.initials: M
authors.lastname: Garajová
authors.affiliation: Department of Zoology, Faculty of Natural Sciences, Comenius University, Mlynská Dolina B-1, 842 15 Bratislava, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Mrva
authors.affiliation: The Oncology Institute "Prof. Dr. Ion Chiricuţă", 400015 Cluj-Napoca, Romania.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Chereches
authors.affiliation: HPL (Ltd), Department of Parasitology, Microbiological Laboratory, Istrijská 20, 841 07 Bratislava, Slovakia.
authors.forename: František
authors.initials: F
authors.lastname: Ondriska
authors.affiliation: Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia.
authors.forename: Marián
authors.initials: M
authors.lastname: Bukovský
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia.
authors.forename: Miloš
authors.initials: M
authors.lastname: Lukáč
authors.affiliation: 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.
authors.forename: Janka
authors.initials: J
authors.lastname: Karlovská
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia.
authors.forename: Janka
authors.initials: J
authors.lastname: Kubincová
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, 832 32 Bratislava, Slovakia.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Devínsky
mesh_terms: D000563:Amebicides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000563:Amebicides; D000970:Antineoplastic Agents; D010767:Phosphorylcholine; C039128:miltefosine
keywords: Acanthamoeba; Alkylphosphocholines; Candida albicans; Cut-off effect; Cytotoxic activity; SAR