title: Synthesis and in vitro cytotoxicity of cross-conjugated prostaglandin A and J series and their hydroxy derivatives.
abstract: The synthesis of two cross-conjugated prostaglandin analogues of known neurotrophic activity and their new hydroxy derivatives was accomplished starting from the diastereoisomeric (+)-camphor protected 3-[(dimethoxyphosphoryl)methyl]-4,5-dihydroxycyclopent-2-enones. The cytotoxicity of these compounds was determined against HeLa, K562, HL-60 human cancer cell lines and normal human cells (HUVEC). We found that NEPP11 and its C7-hydroxy derivative demonstrated high anticancer activity against the HeLa and HL-60 human cancer cell lines at concentrations ranging from 1 to 2 μM. Moreover, the C7-hydroxy derivative of NEPP11 displayed high cytotoxic selectivity between cancer cell lines and normal human cells. On the other hand, the J-type prostaglandin analogue of NEPP11 and its C13-hydroxy derivatives were much less toxic or nontoxic against the cancer and normal cells at concentrations up to 1 mM.
authors.affiliation: Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland. remzur@cbmm.lodz.pl marmikol@cbmm.lodz.pl.
authors.forename: Remigiusz
authors.initials: R
authors.lastname: Żurawiński
authors.forename: Marian
authors.initials: M
authors.lastname: Mikołajczyk
authors.forename: Marcin
authors.initials: M
authors.lastname: Cieślak
authors.forename: Karolina
authors.initials: K
authors.lastname: Królewska
authors.forename: Julia
authors.initials: J
authors.lastname: Kaźmierczak-Barańska
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D018922:HL-60 Cells; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy; D011455:Prostaglandins A, Synthetic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011455:Prostaglandins A, Synthetic