Design and Synthesis of Novel β-Carboline-Bisindole Hybrids as Potential Anticancer Agents

Abstract

We are reporting a short and convenient pathway for the synthesis of novel β-carboline-bisindole hybrid compounds from relatively cheap and commercially available chemicals such as tryptamine, dialdehydes and indoles. These newly designed compounds can also be prepared in high yields with the tolerance of many functional groups under mild conditions. Notably, these β-carboline-bisindole hybrid compounds exhibited some promising applications as anticancer agents against the three common cancer cell lines MCF-7 (breast cancer), SK-LU-1 (lung cancer), and HepG2 (liver cancer). The two best compounds 5 b and 5 g inhibited the aforementioned cell lines with the same IC₅₀ range of the reference Ellipticine at less than 2 μM. A molecular docking study to gain more information about the interactions between the synthesized molecules and the kinase domain of the EGFR was performed. Therefore, this finding can have significant impacts on the development of future research in medicinal chemistry and drug discovery.

Keywords: anticancer agents; antiproliferative activity; bis(3-indolyl)methanes; molecular docking; β-carbolines.