Design, synthesis and anticancer activity evaluation of some novel pyrrolo[1,2-a]azepine derivatives.

A novel series of pyrrolo[1,2-a]azepine derivatives 3-7 were synthesized and their structures were confirmed by spectral and elemental analyses. Antitumor activity evaluation of these compounds was carried out against liver (HepG2), breast (MCF7), and colon (HCT116) cancer cell lines using the sulforhodamine-B (SRB) assay method and doxorubicin as reference standard. Compounds 3 and 6 were found to be more potent than doxorubicin against HepG2 cells, with IC50 values of 4, 1.6 and 10.8 nM, respectively. Moreover, compounds 3 and 7 showed broad-spectrum anticancer activity against all the tested cell lines, and their IC50 values were in the nanomolar range (4-44.2 nM and 20.7-45.4 nM, respectively). The 2-benzoylamino derivative of pyrrolo[1,2-a]azepine 5b was the most potent one against MCF7 cells (IC50 of 10.7 nM); however, the 2-(2-chloro-acetylamino)-pyrroloazepine derivative 6 was the most potent against the HCT116 cell line, with an IC50 value of 21.1 nM. The novel compounds were docked into the active site of cyclin-dependent kinase 2 (CDK2) to explore the ability of these compounds to interact with these kinases. All compounds showed a lower binding score energy than the reference ligand.