title: Unprecedented synthesis, in vitro and in vivo anti-cancer evaluation of novel triazolonaphthalimide derivatives.
abstract: An efficient synthesis method for fusing triazole ring onto the naphthalimide core was described. The anti-cancer activities of the generated triazolonaphthalimide derivatives were evaluated with five cancer cell lines. The compounds generally displayed higher potency than amonafide. 4d,4e carrying two amino side chains showed the strongest cytotoxicities. N-oxide 5, a prodrug of 4a, was designed and synthesized. The agent was expected to be activated under the hypoxic condition in tumor tissue. Compared with 4a, 5 manifested much lower cytotoxicity both in cancer cell lines and human normal cells in the in vitro assays. However, N-oxide 5 performed potent anti-cancer activity in vivo using S-180 sarcoma bearing mice. All the results suggested that 5 was a promising anti-cancer agent.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Li
authors.forename: Wenhe
authors.initials: W
authors.lastname: Zhong
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Li
authors.forename: Xiangbao
authors.initials: X
authors.lastname: Meng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053644:Naphthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011355:Prodrugs / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D053644:Naphthalimides; D011355:Prodrugs