A series of new 6-quinolinyl and quinolinyl N-oxide chalcones were efficiently prepared. All chalcones were tested by minimal inhibitory concentration (MIC) against three species of Candida, Cryptococcus gattii and Paracoccidioides brasiliensis. The effect of these compounds was also tested on the survival and growth of the human cancer cell lines UACC-62 (melanoma), MCF-7 (breast), TK-10 (renal) and leukemic cells, Jurkat and HL60. The compounds tested presented strong activity against P. brasiliensis, most importantly compound 4e. C. gattii also presented interesting susceptibility for compounds 5b and 5f. The cytotoxic activity showed that compounds 3c and 4e, presented the best activity against MCF-7 and TK-10. For leukemic cells the compounds 4f, 3g, 4g and 5g have shown the best activity.