1. Synthesis and evaluation of several new (2-chloroethyl)nitrosocarbamates as potential anticancer agents.
- Author
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Reynolds RC, Tiwari A, Harwell JE, Gordon DG, Garrett BD, Gilbert KS, Schmid SM, Waud WR, and Struck RF
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Carbamates chemistry, Carbamates pharmacology, Drug Screening Assays, Antitumor, Humans, Mice, Neoplasm Transplantation, Nitroso Compounds chemistry, Nitroso Compounds pharmacology, Structure-Activity Relationship, Tumor Cells, Cultured, Antineoplastic Agents chemical synthesis, Carbamates chemical synthesis, Nitroso Compounds chemical synthesis
- 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.
- Published
- 2000
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