Antineoplastic agents. 522. Hernandia peltata (Malaysia) and Hernandia nymphaeifolia (Republic of Maldives).

Abstract

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.

• Authors: George R Pettit, Yanhui Meng, R Patrick Gearing, Delbert L Herald, Robin K Pettit, Dennis L Doubek, Jean-Charles Chapuis, Larry P Tackett
• Journal: Journal of natural products (J Nat Prod) Vol. 67 Issue 2 Pg. 214-20 (Feb 2004) ISSN: 0163-3864 [Print] United States
• PMID: 14987061 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• Lignans
• hernanol

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Crystallography, X-Ray
• Drug Screening Assays, Antitumor
• Humans
• Indian Ocean Islands
• Leukemia P388
• Lignans (chemistry, isolation & purification, pharmacology)
• Malaysia
• Mice
• Microbial Sensitivity Tests
• Molecular Conformation
• Molecular Structure
• Neisseria gonorrhoeae (drug effects)
• Plants, Medicinal (chemistry)
• Trees (chemistry)
• Tumor Cells, Cultured