RESUMEN
The peripheral olfactory tissue (OT) plays a primordial role in the detection and transduction of olfactory information. Recent proteomic and transcriptomic studies have provided valuable insight into proteins and RNAs expressed in this tissue. Paradoxically, there is little information regarding the lipid composition of mammalian OT. To delve further into this issue, using a set of complementary state-of-the-art techniques, we carried out a comprehensive analysis of OT lipid composition in rats and mice fed with standard diets. The results showed that phospholipids are largely predominant, the major classes being phosphatidylcholine and phosphatidylethanolamine. Two types of plasmalogens, plasmenyl-choline and plasmenyl-ethanolamine, as well as gangliosides were also detected. With the exception of sphingomyelin, substantial levels of n-3 polyunsaturated fatty acids, mainly docosahexaenoic acid (22:6n-3; DHA), were found in the different phospholipid classes. These findings demonstrate that the rodent OT shares several features in common with other neural tissues, such as the brain and retina.
Asunto(s)
Ácidos Grasos/análisis , Lípidos/análisis , Mucosa Olfatoria/química , Animales , Cromatografía Liquida , Gangliósidos/análisis , Gangliósidos/química , Lípidos/química , Masculino , Ratones Endogámicos C57BL , Fosfolípidos/análisis , Fosfolípidos/química , Plasmalógenos/análisis , Plasmalógenos/química , Ratas Wistar , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Quinones and quinones-like compounds are potential candidates for the inhibition of CDC25 phosphatases. The combination of MALDI-MS analyses and biological studies was used to develop a rapid screening of a targeted library of indeno[1,2-b]indoloquinone derivatives. The screening protocol using MALDI-TOFMS and MALDI-FTICRMS highlighted four new promising candidates. Biological investigations showed that only compounds 5c-f inhibited CDC25A and -C phosphatases, with IC50 values around the micromolar range. The direct use of a screening method based on MALDI-MS technology allowed achieving fast scaffold identification of a new class of potent inhibitors of CDC25 phosphatases. These four molecules appeared as novel molecules of a new class of CDC25 inhibitors. Assessment of 5c-e in an MRC5 proliferation assay provided an early indicator of toxicity to mammalian cells. Compound 5d seems the most promising hit for developing new CDC25 inhibitors.