title: Synthesis and evaluation of substituted naphthalimide nitrogen mustards as rationally designed anticancer compounds.
abstract: Bromonapmustine 4a and chloronapmustine 4b, two new nitrogen mustards of substituted naphthalimides, have been synthesized as mixed-function anticancer compounds from 4-bromo- and 4-chloro-N-(2-hydroxyethyl)-naphthalimide respectively following a three-step process. Their chemical alkylating activity exceeded that of nor-HN2. Their antitumour efficacy 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 antitumoural activity in these tumours comparable with 5-FU. These compounds inhibit the synthesis of DNA and RNA in S-180 tumour cells. These were further screened in vitro in 3 different human tumour cell lines but no significant activity was observed in those lines.
authors.affiliation: Department of Anticancer Drug Development, Chittaranjan National Cancer Institute, Calcutta-700026, India.
authors.forename: A
authors.initials: A
authors.lastname: Pain
authors.forename: S
authors.initials: S
authors.lastname: Samanta
authors.forename: S
authors.initials: S
authors.lastname: Dutta
authors.forename: A K
authors.initials: AK
authors.lastname: Saxena
authors.forename: M
authors.initials: M
authors.lastname: Shanmugavel
authors.forename: H
authors.initials: H
authors.lastname: Kampasi
authors.forename: G N
authors.initials: GN
authors.lastname: Quazi
authors.forename: U
authors.initials: U
authors.lastname: Sanyal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004273:DNA, Neoplasm / Q000096:biosynthesis; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007094:Imides / Q000138:chemical synthesis* / Q000494:pharmacology; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D004273:DNA, Neoplasm; D007094:Imides; D009588:Nitrogen Mustard Compounds; D012334:RNA, Neoplasm