Structure Activity Relationships of Antiproliferative Rocaglamide Derivatives from Aglaia Species (Meliaceae)

• Published in: Zeitschrift für Naturforschung C. A journal of biosciences Vol. 54; no. 1; pp. 55 - 60
• Main Authors: Bohnenstengel, Frank I., Steube, Klaus G., Meyer, Corinna, Nugroho, Bambang W., Hung, Pham D., Kiet, Le C., Proksch, Peter
• Format: Journal Article
• Language: English
• Published: Germany Verlag der Zeitschrift für Naturforschung 01-01-1999
• Subjects: Aglaia spp; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - toxicity; Antiproliferative Activity; Benzofurans - chemistry; Benzofurans - isolation & purification; Benzofurans - toxicity; Cancer Cells; Cell Survival - drug effects; Cyclopentatetrahydrobenzofurans; Humans; Leukemia, Monocytic, Acute; Melanoma; Meliaceae; Molecular Structure; MONO-MAC-6; Plant Stems; Rocaglamide; Structure-Activity Relationship; Trees; Tumor Cells, Cultured
• ISSN: 0939-5075; 1865-7125
• DOI: 10.1515/znc-1999-1-210

Eleven rocaglamide derivatives (cyclopentatetrahydrobenzofurans) and one structurally related aglain congener all isolated from different Aglaia species (Meliaceae) were tested for growth inhibiting properties using the human cancer cell lines MONO-MAC-6 and MEL-JUSO. Proliferation of both cell lines was efficiently inhibited in a dose and compound dependent manner. Applying a MTT-Assay, the IC
of the most active compound didesmethyl-rocaglamide (1) was observed at 0.002 and 0.006 μg/ml (0.004 and 0.013 μM) depending on the cell line investigated. Bulky aminoacyl substituents at C-2, acetylation of the OH substituent at C-1 or insertion of a OH or OMe substituent at C-3 ’of the rocaglamide skeleton all diminished the activity of the compounds investigated. The aglain derivative 12 was inactive up to a concentration of 3 μg/ml (4.6 μᴍ) . This loss of activity is assumed to be mainly due to the presence of a pyran ring in the aglains vs. a furan ring as found in rocaglamide derivatives. Rocaglamide derivatives may act primarily by inhibition of cell proliferation as evidenced by the absence of a significant cytotoxic effect in long-term cultures of MONO-MAC-6 cells treated with high doses of didesmethylrocaglamide.
Our data suggest that rocaglamide derivatives could exert a potential role in the treatment of malignant diseases and are worth to be investigated in further studies of experimental medicine and pharmacology