Novel benzosuberone conjugates as potential anti-proliferative agents: Design, synthesis and molecular docking studies

Abstract

A series of novel benzosuberone derivatives bearing hexahydrospiro[indoline-pyrrolizin]-ones have been synthesized efficiently by the reaction of corresponding (E)-3-(9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)-1-phenylprop-2-en-1-ones with N-substituted isatins and L-proline in methanol. All the synthesized derivatives were evaluated for their anti-proliferative activity against A549, SKNSH, HeLa, HepG2 and MCF7 human cancer cell lines. The compounds 7h, 7l, 7n, 7p, 7q and 7r exhibited promising activity against all the cell lines and notably, compounds 7l and 7n showed the most potent activity against SKNSH with IC50 values of 4.61 and 5.04 μM. Further, in silico molecular docking [DNA (PDB ID: 1N37)] results stipulated a sign of good correlation between experimental activity and calculated binding affinity, indicating that all the synthesized compounds in particularly compounds 7h, 7l, 7n, 7p, 7q and 7r could be considered as good DNA intercalators. This is the first report on synthesis, in vitro anti-proliferative evaluation of hexahydrospiro[indoline-pyrrolizin]-one hybrids.