lupane and Leukemia-P388

The lupane-type triterpene betulin (1) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence 7→11→12 was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the 11 and 13/14→17 conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer 12 and intermediate 25 are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for 4, 8, 9, 15/16, 19, 20, 24, and 26, which further defines the utility of the betulin scaffold.

Topics: Animals; Antineoplastic Agents, Phytogenic; Betula; Drug Screening Assays, Antitumor; Humans; Leukemia P388; Mice; Molecular Structure; Structure-Activity Relationship; Triterpenes

A new lupane- (1) and a new oleanane-type (2) triterpenoid, together with a known compound, massagenic acid G, were isolated from the cones of Liquidamber styraciflua. The structures of 1 and 2 were determined as 6beta,30-dihydroxy-3-oxolup-20(29)-en-28-oic acid and 3alpha-hydroxy-11-oxoolean-12-en-28-oic acid, respectively, on the basis of spectroscopic methods and chemical conversion. Compound 1 and several structural analogues were evaluated for cytotoxicity against the P388 (murine lymphocyte leukemia) and the A549 (human lung cancer) cell lines.

Topics: Animals; Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; Hamamelidaceae; Humans; Leukemia P388; Mice; Molecular Structure; Oleanolic Acid; Plants, Medicinal; Triterpenes; Tumor Cells, Cultured