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Computer-assisted structure--anticancer activity correlations of carbamates and thiocarbamates
Journal of Pharmaceutical Sciences
|August 1, 1985
Summary
Computer analysis of 8000 anticancer compounds revealed structure-activity relationships for carbamate and thiocarbamate agents. Aromatic derivatives showed promise against P-388 leukemia, with specific substitutions enhancing efficacy.
Area of Science:
- Medicinal Chemistry
- Computational Chemistry
- Pharmacology
Background:
- The National Cancer Institute (NCI) has extensively tested numerous compounds for anticancer properties.
- Carbamate and thiocarbamate moieties are present in various biologically active molecules.
- Understanding structure-activity relationships (SAR) is crucial for drug development.
Purpose of the Study:
- To classify approximately 8000 carbamate and thiocarbamate compounds tested by the NCI.
- To evaluate the structure-activity correlations of these compounds against in vivo P-388 and L-1210 leukemias.
- To identify key structural features responsible for anticancer activity.
Main Methods:
- Utilized computer-aided analysis to classify a large dataset of chemical compounds.
- Performed in vivo testing of selected compounds against P-388 and L-1210 leukemia models.
- Analyzed structure-activity relationships based on chemical structure and biological activity.
Main Results:
- Aromatic carbamates and thiocarbamates demonstrated good activity against P-388 leukemia but poor activity against L-1210 leukemia.
- Optimal activity in aromatic carbamates involved specific heteroatom substitutions on the phenyl ring and N-methylcarbamate groups.
- Bis-N-phenyl carbamates with a methylene bridge showed activity against both leukemia types, while fused phenyl carbamates were generally inactive.
- Certain nitrogen-heterocyclic carbamates and those with heteroatom substituents were selected by the NCI for further development.
Conclusions:
- The study identified specific structural features of carbamates and thiocarbamates that correlate with anticancer activity against P-388 and L-1210 leukemias.
- Heterocyclic carriers and the position of attachment significantly influence the mode of action and antitumor efficacy.
- These findings provide valuable insights for the rational design of novel anticancer agents based on carbamate and thiocarbamate scaffolds.