Synthesis and in vitro anticancer activity evaluation of spiro[indolo[2,1-b]quinazoline-pyrano[2,3-c]pyrazole] via sequential four-component reaction

Abstract

Cancer is still incurable and it is considered as a main health problem worldwide. The identification of novel compounds with high toxicity and low side effects is one of the biggest challenges among interested researchers. In this study, a rapid and simple strategy for synthesis of spiro[indolo[2,1-b]quinazoline-pyrano[2,3-c]pyrazole] derivatives via sequential four-component reaction of isatoic anhydride, isatin, malononitrile, and 3-methyl-pyrazolones in CH2Cl2 at room temperature is described. This procedure has short reaction time and mild reaction conditions. Simple purification and no chromatographic process, are the other notable advantages of this protocol which make it attractive. To evaluate the anticancer activity of our synthetic compounds, pancreatic cancer cell (Panc1), cancer cell of breast (MDA-MB-231), colon cancer cell (HT-29), and normal human adult dermal fibroblast (HDF) were firstly cultured and by using MTT assay, the possible toxicity of related compounds was analyzed. Our results suggested that no compounds have 50% growth inhibitory concentration (IC50) values lower than etoposide (as a reference drug) against all cancer cell lines and among nine synthetic compounds, only 4a compound was effective against Panc1 pancreatic cancer cells.