title: Synthesis and evaluation of 2-chloroethylnitrosoureas of substituted naphthalimides as mixed-function anticancer compounds.
abstract: New mixed function anticancer compounds as 2-chloroethylnitrosoureas of substituted naphthalimides represented by bromonap-NU 4a and chloronap-NU 4b, have been synthesized from 4-bromo- and 4-chloro-l,8-naphthalic anhydride, respectively following a 3-step process. Their chemical alkylating activity compared with nor -HN2 indicated that they possess greater alkylating activity than the latter. Their antitumour efficacies were assessed in vivo in two murine ascites tumours, namely Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Two standard clinical drugs namely endoxan (cyclophosphamide) and 5-fluorouracil (5-FU) were used as positive controls for comparison. Both of them have displayed substantial and reproducible antitumoral activity in these tumours comparable with 5-FU. These were further screened in vitro in 6 different human tumour cell lines but no significant activity was observed in those lines.
authors.affiliation: Department of Anticancer Drug Development & Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India.
authors.forename: S
authors.initials: S
authors.lastname: Samanta
authors.forename: A
authors.initials: A
authors.lastname: Pain
authors.forename: S
authors.initials: S
authors.lastname: Dutta
authors.forename: U
authors.initials: U
authors.lastname: Sanyal
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000401:mortality; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D053644:Naphthalimides; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D012510:Sarcoma 180 / Q000401:mortality; D014407:Tumor Cells, Cultured
chemical_list: C451860:6-bromo-2-(2-(3-(2-chloroethyl)-3-nitrosoureido)ethyl)-1H-benz-(de)isoquinoline-1,3-dione; C451859:6-chloro-2-(2-(3-(2-chloroethyl)-3-nitrosoureido)ethyl)-1H-benz-(de)isoquinoline-1,3-dione; D018906:Antineoplastic Agents, Alkylating; D007546:Isoquinolines; D053644:Naphthalimides; D009607:Nitrosourea Compounds