Synthesis and antiproliferative activities of N-(naphthalen-2-yl)acetamide and N-(substituted phenyl)acetamide bearing quinolin-2(1H)-one and 3,4-dihydroquinolin-2(1H)-one derivatives

Certain N-(naphthalen-2-yl)acetamide and N-(substituted phenyl)acetamide bearing quinolin-2(1H)-one and 3,4-dihydroquinolin-2(1H)-one derivatives have been synthesized and evaluated in vitro for their antiproliferative activities against a panel of human cancer cell lines including nasopharyngeal (NPC-TW01), lung carcinoma (H661), hepatoma (Hep3B), renal carcinoma (A498), and gastric cancer (MKN45). Among them, N-(naphthalen-2-yl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yloxy)acetamide (18) was the most active against NPC-TW01 with an IC50 value of 0.6 μM. Studies on NPC-TW01 cell cycle distribution revealed that compound 18 inhibited proliferation of NPC-TW01 by the alteration of cell division, accumulation of cells in S phase in a time- and concentration-dependent manners. In addition, compound 18 demonstrated very specific cytotoxicity against human nasopharyngeal carcinoma (NPC-TW01) cell lines with no detectable cytotoxicity against peripheral blood mononuclear cells (PBMCs) at a concentration of up to 50 μM.

Graphical abstractIC50 = 0.6 μM against NPC-TW01.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Quinolin-2(1H)-one derivatives were synthesized for antiproliferative evaluations. ► Compound 18 was the most active against NPC-TW01 with an IC50 value of 0.6 μM ► Compound 18 was non cytotoxic against PBMCs at a concentration of up to 50 μM ► Compound 18 inhibited NPC-TW01 proliferation by cell accumulation in S phase.