Synthetic Transformations of Higher Terpenoids. 44#. Synthesis of New Derivatives of 18-Nor-4-Amino-8(17),13,14-Labdatriene and Evaluation of Their Cytotoxicity for MCF7, HepG2, and HeLa Tumor Cell Lines

Abstract

Various N-containing 18-norlabdanoids were synthesized via reactions of 18-nor-4-amino-15,16-epoxy-8(17),13(16),14-labdatriene with methyl iodide, aromatic aldehydes, acetic and trifluoroacetic acid anhydrides, benzoyl chloride, sulfonyl chlorides, bromoacetic acid chloride, and methyl bromoacetate and condensation with azidobenzoic acids. The cytotoxic activity (MTT assay) against MCF7, HepG2, and HeLa tumor cell lines was shown to increase significantly if the lambertianic acid carboxylic group was replaced by an amine. Subsequent modification of the N-containing substituent by addition of an N′-substituted glycylamide moiety altered the cytotoxicity and selectivity. The synthesized compounds had the greatest effect on the viability of MCF7 cell line. The IC₅₀ value for the most active compound was 8 μM.