Anticancer evaluation of 4-substituted-N-(quinolin-8-yl)pyridine-3-sulfonamides

During our research over biological activity of different N-aryl-4-substututed-pyridine-3-sulfonamides we have found that compound bearing N-(quinolin-8-yl) substituent possess a significant anti-tumor activity. Mechanisms of anticancer activity of N-(quinoline)sulfonamide derivatives was reported to be inhibition of NF-κB pathway. Nuclear factor NF-κB regulates expression of genes that control cell proliferation and cell survival thus it is consider as potential molecular targets for the prevention and treatment of cancer. Based on this information we decided to synthesize and evaluate series of 4-amino-N-(quinolin-8-yl)pyridine-3-sulfonamides, which contain both 8-amonoquinolin group and pyridine-3-sulfonamide scaffold.

Target compounds were obtained in multistep reaction starting from 4-hydroxypyridine, and their structure was confirmed using the spectroscopic methods: IR, ¹H NMR, and elemental analysis (C, H, N), Synthesized compounds were tested using MTT assay towards their effect on growth of three human cancer cell lines: colon cancer HCT-116, breast cancer MCF-7 and cervical cancer HeLa as well as on noncancerous keratinocyte cell line HaCaT. Cell viability was measured after 72 h of incubation with tested compound in five concentration 1 – 100 μM.

All compounds show very high activity comparable to cisplatin against cancer cells lines (IC₅₀=4-43 μM), and selectivity relative to HaCaT cells.