RESUMO
A multicomponent diversity-oriented synthesis of new highly emissive tetracyclic isoquinolines that target specific organelles is described. The title compounds were prepared via a three-step protocol starting with an Ugi four-component reaction, followed by either an intramolecular alkyne hydroarylation and subsequent alkene isomerization or through a Pomeranz-Fritsch-type cyclization with a final intramolecular Heck reaction. Subcellular localization studies of these compounds using green channel confocal microscopy revealed remarkable and distinctive distribution patterns in live cells, showing an unprecedented high selectivity and imaging contrast. The differentiated organelle visualization-including localizers for mitochondria, lysosomes, Golgi apparatus, endoplasmic reticulum, and plasma membrane-was achieved by varying the nature of the tetracyclic system and substituent pattern, changing the original four-component set in the starting Ugi reaction.
Assuntos
Corantes Fluorescentes/química , Isoquinolinas/síntese química , Isoquinolinas/metabolismo , Frações Subcelulares/metabolismo , Células HeLa , Humanos , Isoquinolinas/químicaRESUMO
Four novel miconazole analogues (8-11) were synthetized and evaluated for activity against four filamentous fungi (Mucor hiemalis, Aspergillus fumigatus, Trichosporon cutaneum, and Rhizopus oryzae) and eight species of Candida as yeast specimens. Compounds 9 and 10 showed very good activity when evaluated in yeast (MIC 0.112 and 0.163 µg/mL) compared to the reference compound, itraconazole (MIC 0.067 µg/mL). The best antifungal activity in filamentous strains was shown by compound 9. Hence compounds 9 and 10 represent new leads for further pharmacomodulation in this series.