An efficient, convenient synthesis of novel medium-sized 13H-dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione macrolides as anticipated antineoplastic agents Original Research Article

A series of novel medium-sized 13H-dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione macrolides (18–27, 30, 32) were synthesized in an ongoing effort to develop new antineoplastic agents. The synthon 2-(2-aminobenzoylamino)-benzoic acid (7), for preparation of the target compounds, was prepared via the reaction of isatoic anhydride 5 and anthranilic acid 6. Nine compounds (18–20, 24–27, 30, 32) were subjected to National Cancer Institute (NCI) in vitro disease-oriented human cells screening panel assay. Among the compounds tested, 6-benzyl-13H-dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione (26, NSC 721327), bearing the benzyl group at position 6, showed cytotoxic activity and subpanel selectivity against leukemia (CCRF-CEM), colon (HCC-2998), CNS (SNB-75) and melanoma (UACC-257) panels at log10 GI50 (M), compound concentration that inhibits 50% of cell growth, ranging from −4.08 to −4.59.