Sequential Four-Component Synthesis And Antitumor Activity Screening of Spiro[chromene-indolo[2,1-b]quinazoline] And Spiro[indolo[2,1-b]Quinazoline-pyrano[3,2-c]chromene]

Abstract Chemotherapy is one of the most common types of treatment among cancer patients and by using potent chemicals and agents, tumor promotion was inhibited. Despite the usage of many chemical agents in cancer therapy, cancer is still incurable. It seems that the synthesis of new compounds with high efficiency on cancer cells and low side effects on normal cells will remain a critical challenge among researchers in this area. In the present work, a fast and straightforward process for the transformations involving tryptanthrins, malononitrile, some types of CH-acids such as 1,3-cyclohexanedione, dimedone, and 4-hydroxycumarin resulting in preparing spiro[chromene-indolo[2,1-b]quinazoline] and spiro[indolo[2,1-b]quinazoline-pyrano[3,2-c]chromene] derivatives through sequential Knoevenagel/Michael/intramolecular cyclization sequences was reported. at room temperature. This protocol benefits some notable advantages including short reaction time, mild reaction condition, and simple purification, which make it interesting. Furthermore, it was carried out at room temperature, so it is according to green chemistry procedures. Also, antitumor screening of our new synthetic compounds (4a-i) was evaluated on pancreatic cancer cells (Panc1), breast cancer cells (MDA-MB-231), prostate cancer cells (PC3), and normal human adult dermal fibroblast cells (HDF) by using MTT assay using etoposide as a positive control. We found that 50% growth inhibitory concentration (IC50) values of our synthetic compounds were not lower than etoposide against three cancer cell lines.