Synthesis and Evaluation of Several New (2-Chloroethyl)nitrosocarbamates as Potential Anticancer Agents

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 line...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2000-04, Vol.43 (8), p.1484-1488
Main Authors: Reynolds, Robert C, Tiwari, Anita, Harwell, Joyce E, Gordon, Deborah G, Garrett, Beverly D, Gilbert, Karen S, Schmid, Steven M, Waud, William R, Struck, Robert F
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Carbamates - chemical synthesis
Carbamates - chemistry
Carbamates - pharmacology
Drug Screening Assays, Antitumor
General aspects
Humans
Medical sciences
Mice
Neoplasm Transplantation
Nitroso Compounds - chemical synthesis
Nitroso Compounds - chemistry
Nitroso Compounds - pharmacology
Pharmacology. Drug treatments
Structure-Activity Relationship
Tumor Cells, Cultured
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Summary: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 IC50 values in the range of 1−10 μg/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-α,β-d-glucopyranose ester (24) were evaluated against subcutaneously implanted M5076 murine sarcoma in mice. None of these compounds were active in vivo.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm990417j