Synthesis and evaluation of 1-acyl-1,2-bis(methylsulfonyl)-2-(2- chloroethyl)hydrazines as antineoplastic agents.

doi:10.1021/JM00075A002

Paper

Synthesis and evaluation of 1-acyl-1,2-bis(methylsulfonyl)-2-(2- chloroethyl)hydrazines as antineoplastic agents.

Published Nov 12, 1993 · K. Shyam, P. Penketh, A. Divo

Journal of medicinal chemistry

Q1 SJR score

25

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0

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Abstract

A series of 1-acyl-1,2-bis(methylsulfonyl)-2-(2-chloroethyl)hydrazines, conceived as more potent analogs of 1-(2-chloroethyl)-1,2,2-tris(methylsulfonyl)hydrazine, were synthesized and evaluated for antineoplastic activity against the L1210 leukemia in mice. Of these, 1-acetyl-1,2-bis-(methylsulfonyl)-2-(2-chloroethyl)hydrazine produced "cures" of mice bearing the L1210 leukemia at dosage levels that were considerably less than those at which the tris(sulfonyl) analog produced its antineoplastic effects. This compound was also found to have pronounced activity against the P388 leukemia and against several solid tumors, including the B16F10 melanoma, the M5076 reticulum cell sarcoma, and the M109 lung carcinoma. Furthermore, the acyl derivatives were in general considerably more resistant to hydrolysis in aqueous media and more prone to protease- and thiol-mediated activation than the tris(sulfonyl) analog. The former property is important to formulation, while the latter properties may result in some degree of drug targeting and enhancement of the therapeutic indices of these agents.

Non-RCT

Animal Study

Study Snapshot

1-acetyl-1,2-bis-(methylsulfonyl)-2-(2-chloroethyl)hydrazine shows promising antineoplastic activity against L1210 leukemia, P388 leukemia, and various solid tumors, with potential for improved formulation and targeting

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Synthesis and evaluation of 1-acyl-1,2-bis(methylsulfonyl)-2-(2- chloroethyl)hydrazines as antineoplastic agents.

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References

Citations

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