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pubmed:abstractText |
Starting from 4-tetradecyloxybenzamidine (PMS815), a non-specific inhibitor of GI and GII PLA2s, we report in this work the discovery of the specificity through design, synthesis and structure-activity relationships studies of different kinds of PMS815 derivatives. The leading compound, 4,5-dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one (9b, PMS1062) exhibits a micromolar IC50 towards three group II PLA2s, while inactive towards four group I and one group III enzymes in two in vitro enzymatic assay conditions. It is also able to block the PLA2-II activities induced by LPS and IL-6 in HepG2 cell line and no cytotoxicity is observed when PMS1062 is tested up to a concentration of 100 microM in two different cell lines (A549 and LLC-PK1).
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pubmed:affiliation |
Unité de Pharmacochimie Moléculaire et Systèmes Membranaires (EA2381), Laboratoire de Pharmacochimie Moléculaire, Université Paris 7 - Denis-Diderot, case 7066, 2, place-Jussieu, 75251 Paris cedex 5, France.
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