Antitumor Agents XXX: Evaluation of α-methylene-γ-lactone-Containing Agents for Inhibition of Tumor Growth, Respiration, and Nucleic Acid Synthesis

Abstract

Evidence is presented that a number of sesquiterpene lactones isolated from plants and synthesized pyrimidines containing the α-methylene-γ-lactone moiety are potent inhibitors of Walker 256 carcinosarcoma and Ehrlich ascites tumor growth and marginal inhibitors of P-388 lymphocytic leukemia and Lewis lung tumor growth. In vitro aerobic basal respiration and oxidative phosphorylation processes of Ehrlich ascites cells were inhibited by these agents as well as deoxyribonucleic acid polymerase and thymidylate synthetase enzymatic activities. These studies indicate that the α-methylene-γ-lactone moiety, the β-unsubstituted cyclopentenone ring, and the α-epoxycyclopentanone system are the essential moieties for inhibition of these biochemical parameters.