Design, Synthesis, and Anticancer and Antibacterial Activities of Quinoline-5-Sulfonamides.

A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide - and - were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems - were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide - with organic azides. The structures of the obtained compounds were confirmed by H and C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives - and - and 1,2,3-triazole derivatives - were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains ATCC 29213 and ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant (MRSA) and vancomycin-resistant . Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide - were shown to be biologically active, and 8-hydroxy--methyl--(prop-2-yn-1-yl)quinoline-5-sulfonamide () showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC of 100 µM. In additional tests, compound decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity.