kolavenic-acid and 16-hydroxycleroda-3-13(14)-dien-15-16-olide

The stem bark of Polyalthia simiarum has yielded a new bisnor-type clerodane diterpenoid, 2-oxo-14,15-bisnor-3,11E-kolavadien-13-one (1), and three previously known clerodane derivatives, kolavenic acid (2), 16beta-hydroxycleroda-3,13(14)Z-dien-15,16-olide (3), and 16-oxocleroda-3,13(14)E-dien-15-oic acid (4). The structures of these compounds were unambiguously determined by extensive NMR studies as well as by comparison with related compounds. Till now this is the second report of the occurrence of any unusual C-18 clerodane diterpenoid from nature. The crude light petroleum extract and the purified compound 3 demonstrated moderate free radical scavenging activity with IC50 values of 21.5 and 23.5 microg/mL, respectively.

Topics: Diterpenes; Diterpenes, Clerodane; Polyalthia

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).

Topics: Antineoplastic Agents, Phytogenic; Diterpenes; Drug Screening Assays, Antitumor; Humans; Plants; Tumor Cells, Cultured