Design, synthesis and biological evaluation of spiroisoquinoline-pyrimidine derivatives as anticancer agents against MCF-7 cancer cell lines

Quinoline derived scaffolds have long been reported for their promising biological responses such as anti-Alzheimer, antituberculosis, antioxidants, anti-inflammatory etc. Pyrimidine, a versatile pharmacophore, has also been employed for developing a variety of bioactive molecules. Therefore, we envisioned to incorporate these two privileged moieties into a single one for improved biological applications. In this work, we developed an efficient catalyst free synthesis of spiroisoquinlino-pyrimidine conjugates via one-pot multicomponent reaction of various 1,3-dicarbonyls, isoquinoline and dialkyl acetylene dicarboxylates. We further evaluated anti-proliferative activity of all the compounds against MCF-7 human breast cancer cells. Out of several compounds synthesized, three compounds IVc, IVg and IVi having substituent methyl and dioxyl ring in molecule have shown potent anticancer activity. The most potent cytotoxic compound against breast cancer cells in our study was found to be IVi with IC50 value of 98.8 mu M.

Automated summary

This study developed an efficient catalyst-free synthesis method to combine the Quinoline and Pyrimidine pharmacophores into a single molecule for improved biological applications. Among the synthesized compounds, three compounds with methyl and dioxyl ring substitutions showed potent anticancer activity, with IVi being the most effective compound against breast cancer cells.