Cytotoxic clerodane diterpenes from Polyalthia longifolia

Bioassay-directed chemical investigation of the stem bark of Polyalthia longifolia Thw. (Annonaceae) has led to a novel clerodane diterpene, 16-oxo-cleroda-3, 13(14)Z-dien-15-oic acid, which was named polyalthialdoic acid (3). The bioassays also led to the previously known related diterpenes, kolavenic acid (2) which has not been reported as a constituent of this plant, and 16 alpha-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (1) which is previously known to be in this plant. These structures were identified by chemical and spectroscopic methods. All three compounds (1-3) were significantly bioactive in the brine shrimp bioassay; they strongly inhibited the growth of crown gall tumors on potato discs; and they were cytotoxic in three human tumor cell lines. These activities suggest potential antitumor applications. Compound 3 was the most active (ED50 values ca. 6 x 10(-1) micrograms/ml in the human tumor cell culture systems).