An efficient, convenient synthesis of novel medium-sized 13H-dibenzo[d,h][1,3,7]oxadiazecine-8,14-dione macrolides as anticipated antineoplastic agents.
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 log(10) GI(50) (M), compound concentration that inhibits 50% of cell growth, ranging from -4.08 to -4.59.
Abdel-Hafez
Atef Abdel-Monem
AA
Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. atef@acc.aun.weun.eg
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013057:Spectrum Analysis; D014407:Tumor Cells, Cultured
C465522:13H-dibenzo(d,h)(1,3,7)oxadiazecine-8,14-dione; D000970:Antineoplastic Agents; D018942:Macrolides