Antineoplastic agents. 522. Hernandia peltata (Malaysia) and Hernandia nymphaeifolia (Republic of Maldives).
Bioassay (P388 lymphocytic leukemia cell line and human tumor cell lines)-guided separation of the extracts prepared from the tropical and coastal trees Hernandia peltata (Malaysia) and Hernandianymphaeifolia (Republic of Maldives) led to the isolation of a new lignan designated as hernanol (1) and 12 previously known lignans: (-)-deoxypodophyllotoxin (2), deoxypicropodophyllin (3), (+)-epiaschantin (4), (+)-epieudesmin (5), praderin (6), 5'-methoxyyatein (7), podorhizol (8), deoxypodorhizone (9), bursehernin (10), kusunokinol (11), clusin (12), and (-)-maculatin (13). The oxidative cyclization (with VOF(3)) of lignans 8, 9, and 10 resulted in a new and unusual benzopyran (14), isostegane (15), and a new dibenzocyclooctadiene lactone (16), respectively. The structure and relative stereochemistry of hernanol (1) and lignans 3, 7, 8, 9, 10, 11, and 12 were determined by 1D and 2DNMR and HRMS analyses. The structures and absolute stereochemistry of structures 2, 4, 5, 6, 13, 14, 15, and 16 were unequivocally determined by single-crystal X-ray diffraction analyses. Evaluation against the murine P388 lymphocytic leukemia cell line and human tumor cell lines showed podophyllotoxin derivatives 2 and 3 to be strong cancer cell line growth inhibitors and substances 4, 5, 8, and 15 to have marginal cancer cell line inhibitory activities. Seven of the lignans and one of the synthetic modifications (14) inhibited growth of the pathogenic bacterium Neisseria gonorrhoeae.
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-2404, USA. bpettit@asu.edu
Meng
Yanhui
Y
Gearing
R Patrick
RP
Herald
Delbert L
DL
Pettit
Robin K
RK
Doubek
Dennis L
DL
Chapuis
Jean-Charles
JC
Tackett
Larry P
LP
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007195:Indian Ocean Islands; D007941:Leukemia P388; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008296:Malaysia; D051379:Mice; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D015394:Molecular Structure; D009344:Neisseria gonorrhoeae / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D014197:Trees / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D017705:Lignans; C483798:hernanol