E. Dilip de Silva

Manoalide, an antibiotic sesterterpenoid from the marine sponge (polejaeff)

Abstract The structure of manoalide ( 1 ), a new sesterterpenoid antibiotic isolated from a marine sponge, has been determined by spectral analysis and chemical transformations.

Motuporin, A Potent Protein Phosphatase Inhibitor Isolated from the Papua New Guinea Sponge Theonella swinhoei Gray

Abstract Motuporin ( 1 ), a cyclic pentapeptide that is a potent protein phosphatase-1 inhibitor and cytotoxin, has been isolated from the marine sponge Theonella swinhoei collected in Papua New Guinea. The structure of motuporin was elucidated by spectroscopic analysis and chemical degradation.

Cytotoxic peptides from the marine sponge Cymbastela sp.

Abstract Extracts of the sponge Cymbastela sp. have yielded the novel cytoloxic peptides geodiamolide G (II), hemiasterlin A (12), hemiasterlin B (13), criamide A (14) and criamide B (15). The structures of the new compounds were solved via speciroscopic analysis and chemical degradation.

geodiamolides C to F, new cytotoxic cyclodepsipeptides from the marine sponge Pseudaxinyssa sp.

Abstract Four new cytotoxic cyclodepsipeptides, geodiamolides C (3) to F (6), have been isolated from the sponge Pseudaxinyssa sp. collected in Papua New Guinea. The structures of metabolites 3 to 6 have been solved by spectroscopic analysis.

Cytotoxic alkaloids from the flatworm Prostheceraeus villatus and its tunicate prey Clavelina lepadiformis

Abstract Four novel alkaloids, lepadins B ( 2 ) and C ( 3 ) and villatamines A ( 4 ) and B ( 5 ), have been isolated from the predatory flatworm Prostheceraeus villatus and its tunicate prey Clavelina lepadiformis. Lepadins A ( 1 ) and B ( 2 ) and villatamine B ( 5 ) exhibit significant in vitro cytotoxicity against human cancer cell lines.

Ambewelamides A and B, antineoplastic epidithiapiperazinediones isolated from the lichen Usnea sp.

Abstract Two potently cytotoxic epidithiapiperazinediones, ambewelamides A ( 1 ) and B ( 2 ), have been isolated from the lichen Usnea sp. collected in Sri Lanka. The structures were determined by a combination of X-ray crystallographic and spectroscopic analyses.

Helvolic acid, an antibacterial nortriterpenoid from a fungal endophyte, Xylaria sp. of orchid Anoectochilus setaceus endemic to Sri Lanka.

An endophytic fungus was isolated from surface sterilized leaf segments of Anoectochilus setaceus, an orchid endemic to Sri Lanka, and was identified as Xylaria sp. by morphological characters and DNA sequencing. Bioassay-guided chromatographic fractionation of the organic extract of a laboratory culture of this fungus led to the isolation of the known antibacterial helvolic acid. Helvolic acid was active against the Gram-positive bacteria, Bacillus subtilis [minimal inhibitory concentrations (MIC), 2 µg mL−1] and methicillin-resistant Staphylococcus aureus (MIC, 4 µg mL−1).

Isolation of 2-pyridone alkaloids from a New Zealand marine-derived penicillium species.

Fermentation of a Penicillium sp. isolated from a surface-sterilized thallus segment of the brown alga Xiphophora gladiata, collected from Macrocarpa Point, Otago, New Zealand, in half-strength potato dextrose broth led to the isolation and characterization of three alkaloids: the known N-hydroxy-2-pyridone, PF1140 (1), and two new 2-pyridones, 2 and 3.

Dhilirolides A-D, meroterpenoids produced in culture by the fruit-infecting fungus Penicillium purpurogenum collected in Sri Lanka.

Dhilirolides A (1) to D (4), a family of secondary metabolites with a putative meroterpenoid biogenetic origin and the unprecedented dhilirane and isodhilirane carbon skeletons, have been isolated from laboratory cultures of the fruit-infecting fungus Penicillium purpurogenum collected in Sri Lanka. The structures of 1 to 4 were elucidated by interpretation of NMR data and a single crystal X-ray diffraction analysis of 1.

Anticancer Agents from Unique Natural Products Sources

The National Cooperative Natural Products Drug Discovery Group (NCNPDDG) “Anticancer Agents from Unique Natural Products Sources, CA 67786” was first awarded in September 1995. The goal of the project is to discover and develop novel anticancer agents from a variety of natural products sources. The key accomplishments of this NCDDG which will be highlighted in this manuscript include: Development of tools to probe fungi for the production of novel natural products by DNA-based probes. Discovery that the majority of these fungi can produce natural products via nonribosomal peptide synthetases, polyketide synthases, or both – a much larger percentage than current culturing techniques reveal. Identification of the MDR-selective cytotoxic agent austocystin D, and use of a novel yeast deletion strain approach to help identify its molecular target(s). Identification of hemiasterlin and other naturally occurring analogs as potent antimitotic agents with excellent in vivo activity against human solid tumors in mouse models. Development of a total synthesis of hemiasterlin. The utilization of this methodology to provide the first SAR for the hemiasterlin family of antimitotic agents and to identify the synthetic analog HTI-286, which is being examined in clinical trials as an anticancer agent. To provided technology transfer, educational opportunities and compensation to countries of origin for collection and study of their natural product resources. This NCNPDDG program has provided funding to research programs at the University of the Philippines, The University of the South Pacific in the Fiji Islands, Colombo University in Sri Lanka, the Instituto de Quimica de Sao Carlos, Universidade de Sao Paulo, Brazil, and the University of Papua New Guinea.