title: Synthesis and evaluation of several new (2-chloroethyl)nitrosocarbamates as potential anticancer agents.
abstract: Seven new (2-chloroethyl)nitrosocarbamates have been synthesized as potential anticancer alkylating agents. These compounds were designed with carrier moieties that would either act as prodrugs or confer water solubility. All compounds were screened in an in vitro panel of five human tumor cell lines: CAKI-1 (renal), DLD-1 (colon), NCI-H23 (lung), SK-MEL-28 (melanoma), and SNB-7 (CNS). Several agents showed good activity with IC(50) values in the range of 1-10 microg/mL against at least two of the cell lines. One compound, carbamic acid, (2-chloroethyl)nitroso-4-acetoxybenzyl ester (3), was selected for further study in vivo against intraperitoneally implanted P388 murine leukemia. In addition to the aforementioned compound, both carbamic acid, (2-chloroethyl)nitroso-4-nitrobenzyl ester (9) and carbamic acid, (2-chloroethyl)nitroso-2,3,4, 6-tetra-O-acetyl-1-alpha,beta-D-glucopyranose ester (24) were evaluated against subcutaneously implanted M5076 murine sarcoma in mice. None of these compounds were active in vivo.
authors.affiliation: Drug Discovery and Drug Development Divisions, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama 35255-5305, USA. reynolds@sri.org
authors.forename: R C
authors.initials: RC
authors.lastname: Reynolds
authors.forename: A
authors.initials: A
authors.lastname: Tiwari
authors.forename: J E
authors.initials: JE
authors.lastname: Harwell
authors.forename: D G
authors.initials: DG
authors.lastname: Gordon
authors.forename: B D
authors.initials: BD
authors.lastname: Garrett
authors.forename: K S
authors.initials: KS
authors.lastname: Gilbert
authors.forename: S M
authors.initials: SM
authors.lastname: Schmid
authors.forename: W R
authors.initials: WR
authors.lastname: Waud
authors.forename: R F
authors.initials: RF
authors.lastname: Struck
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009603:Nitroso Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D009603:Nitroso Compounds