Ambewalamides A and B, Novel Antineoplastic Compounds from a Sri Lankan USNEA SP
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Date
1998-11-07
Authors
Karunaratne, V.
Bombuwala, K.
De Silva, E. D.
Journal Title
Journal ISSN
Volume Title
Publisher
University of Peradeniya
Abstract
Department of Chemistry, University of Peradeniya *Department of Chemistry, University of Colombo
Lichens produce a wide range of natural products and many are unique to lichens and an appreciable number have been shown to have antimicrobial, and other biological activities of potential medicinal value.
The present study describes the isolation of two novel endodisulphides from an Usnea species. Specimens of the Usnea sp. were collected from the surface of a decaying tree, identified asAcacia deccurens in Ambewala, Central Province, Sri Lanka. The air- dried lichen (950 g) was exhaustively extracted with CH2Cl2 at room temperature to give a crude gum (5.1 g) that was fractionated via silica gel medium pressure liquid chromatography (eluent: step gradient from hexane to MeOH/CH2CI2, 4:96), silica gel preparative chromatography (eluent CH2CI2) and Sephadex LH-20 chromatography (eluent: CH2CI2/MeOH, 2:8) to give a crystalline fraction that contained the mixture of ambewelamides A and B. Final purification was accomplished using normal phase HPLC (Waters Radical PAK cartridge; eluent: CH2CI2/McOH, 20: 1) to give 13.4 mg of ambewelamide A and 1.4 mg of anbewelamide B, both as optically active, clear crystalline plates.
The structure of the compounds were elucidated by a combination of high resolution FAB mass spectroscopy, and lD and 2D NMR (COSY & HMBC) spectroscopy. The final confirmation was arrived at by single crystal X-ray diffraction techniques. Ambewelarnide A exhibited potent in vitro cytotoxicity (murine leukemia P388: IC50 = 8.6 ng/ml.) and it also showed significant in vivo antineoplastic activity (P388: % CIT 140 @ 160 ~lg/Kg). To [he best of our knowledge, this is the most potent and most promising anticancer compound to be discovered from a Sri Lankan source (both terrestrial and marine).
Diagram(See the pdf version of the Scanned copy)
Ambewelamide A: R = (CHz) ZCH3
Ambewelamide B: R = (CHz) 4CH3
Description
Keywords
Ambewalamides , Lichens , Antineoplastic compounds , Physical sciences , engineering and technology
Citation
Proceedings & Abstracts of the Annual Research Sessions 1998, University of Peradeniya, Peradeniya, Sri Lanka, pp.85