New tricyclic pyrone derivatives were synthesized and tested for their ability to prevent L1210 leukemic cells from synthesizing
DNA and growing in vitro. At 50 microM, a pyripyropene analog has no effect, whereas four pentahydro-3-aryl-1-oxopyrano[4,3-b][1]
benzopyrans all inhibit
DNA synthesis by 79-91% and
tumor cell growth by 93-100%. These inhibitory effects are concentration dependent with IC50 around 8.5 microM for
DNA synthesis at 2 hours and 1.1 microM for
tumor cell growth at 4 days. The aryl groups of these
antitumor agents are either 3,4-dimethoxyphenyl or 3-pyridyl. Introduction of a methyl group at C5a and a formyloxy or hydroxy group at C6 does not alter the antitumor effects of the 3,4-dimethoxyphenyl
benzopyrans but reduces those of the 3-pyridyl
benzopyrans, which, at 50 microM, inhibit
DNA synthesis by only 32-49% and fail to alter
tumor cell growth. The 4-hydroxy-6-(3-pyridyl)-2-pyrone has no effect and the
tricyclic pyrones lacking aryl groups have very little inhibitory effects on
DNA synthesis, suggesting that a greater conjugation is required for the antitumor activity. These molecules have never been reported and might be valuable to develop a new class of anticancer drugs.