A new method for the synthesis of 6,7-dihydro-5H-pyrrolo[2,1-a][2]benzazepines and 5,6,7,9,10,11-hexahydro-12H-indolo[2,1-a][2]benzazepines and evaluation of their bioactivity

Abstract

This article describes a new method for the synthesis of pyrrolo[2,1-a][2]benzazepine and indolo[2,1-a][2]benzazepine derivatives with different pyrrole fragment structures containing functional groups. The method is based on domino reactions involving the imino-ketone fragment of 1-aroyl-4,5-dihydro-3H-[2]benzazepines and electron-deficient alkenes and alkynes. The anticancer and anti-inflammatory activities of synthesized compounds were evaluated. These compounds displayed significant toxicity to four cancer cell lines (including RD, HCT116, HeLa and A549 ones). Amongst these compounds, 3b–e had the best inhibitory activity against the tested cancer cell lines with IC₅₀ values ranging from 4.52 to 19.97 µM, Notably, compound 3b demonstrated the most potent inhibitory effect on nitric oxide (NO) production, with an IC value of only slightly higher than those of the reference compound L-NMMA. Furthermore, molecular docking studies revealed the important interaction of four compounds 3b–e with residues in the etoposide-binding site of topoisomerase as well.