Catalyst-free and multicomponent synthesis of 3-aminoalkylated indoles via a Mannich-type reaction: multitargeted anticancer, tyrosinase and α-glucosidase inhibitory activities

Abstract

A highly efficient and sustainable approach for the multi-component synthesis of 3-aminoalkylated indoles was investigated via a Mannich-type reaction under catalyst-free conditions, with methanol and ethylene glycol (EG) as the promoting media. Synthesizing various substrates without using column chromatography is time-saving and convenient, which is one of the advantages of this method. In addition, the environmental friendliness is also considered in this research. The synthetic indole derivatives 4a–g and 5a–g, confirmed via spectral analysis, were investigated for their in vitro anticancer activity on human cancer cell lines such as lung (A549), breast (MDA-MB-231) and prostate (PC3) as well as their antityrosinase and α-glucosidase inhibitory activities. Specifically, the results showed that most of the synthesized indoles inhibited both carcinoma and adenocarcinoma cell lines and affected the cytotoxic activity against all three cancer cell lines in the same fashion; moreover, compounds 5e and 5f were shown to be multitargeted anticancer agents. The results of molecular docking studies clarified that the binding of the most potent compounds, 5e and 5f, at the TopI–DNA binding site was through hydrogen bonding as well as hydrophobic interactions and is comparable to camptothecin binding.