Leu T.* 1, Soulet S. 1, Herbette G. 2, Faure R. 2, Bianchini J.-P. 1, Meijer L. 3 and Raharivelomanana P 1. * to: 1 Laboratoire.

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Leu T.* 1, Soulet S. 1, Herbette G. 2, Faure R. 2, Bianchini J.-P. 1, Meijer L. 3 and Raharivelomanana P 1. * to: 1 Laboratoire Biotem EA 4239, Université de la Polynésie Française, BP 6570, Faa’a, Tahiti, French Polynesia 2 Spectropole de Marseille, Université Paul Cézanne, Marseille Cedex 20, France 3 Station Biologique de Roscoff, CNRS/USR 3151, Place G. Tessier, BP 74, 29682, Roscoff, Cedex, France GA 2009 Elastase inhibitors and cancer preventive potential agents from Calophyllum inophyllum (L.) grown in French Polynesia Introduction: Experimental.  Resin of Tamanu was extracted from seed oil with 96 ° EtOH and neutral fraction was separated from the acidic one (fig. 1 ).  Products of NRT and ART were isolated by chromatographic methods and identified by spectroscopic analyses (UV, IR, HRMS, 1 D and 2 D NMR).  In vitro enzymatic inhibition assay was carried out at different steps of purification.  Bioguided fractionation led to the isolation of new elastase inhibitory compounds. Fig 1: Separation of resins from Tamanu oil References: 1.Barnes, P.J., Hansel, T.T. (2004) The Lancet 364: Akli, S., Keyomarsi, K. (2004) Br Cancer Res 6: Pétard, P. (1986) Plantes utiles de Polynésie – Raau Tahiti, Editions Haere Po No Tahiti, Papeete, Tahiti. 4.Laure, F. et al. (2008) Anal Chim Act 624: Acknowledgement: The Ministère chargé de la Recherche en Polynésie française is greatly acknowledge for financial support (Convention n°5.0314/PR du 30/11/05, avenant n°6.0360/PR du 24/08/06). The authors are also grateful to Dr. J.-Y. Meyer and Dr. P. Frogier for helpful commentaries. Conclusions.  16 coumarin derivatives were identified from the resin of Tamanu including the new tamanolides and the firstly occuring in C. inophyllum calanolides.  Among those, 5 compounds led to significant inhibition of elastase, the most active compound being calophyllolide.  Phenyl C-4 susbtituent and opened D-ring are structural requirements for elastase inhibition by coumarin derivatives. Elastase is a serin endo-proteinase responsible for extracellular matrix proteins degradation. Overexpression was linked to COPD, Cystic Fibrosis 1 and associated to increased low- molecular weight form Cyclin E correlating with poor diagnosis and morbidity increase in breast cancer 2.  Calophyllum inophyllum, L.  Division: Magnoliophyta  Class: Magnoliopsida  Order: Theales  Family: Clusiaceae  Genus: Calophyllum  Species: C. inophyllum Tamanu (C. inophyllum) is a pantropical species widely used in Polynesian folk medicine for skin treatments, wound healing and as pain killer 3. Previous studies have shown the presence of bioactive coumarin derivatives 4.  Elastase. Enzymatic screening assay revealed elastase inhibiting properties of fractions of Tamanu oil. Bioguided phytochemical investigations led to the identification of elastase inhibiting new pyranocoumarin compounds. CalophyllolideInophyllum CInophyllum EInophyllum PInophyllum D Calanolide « No name »Calanolide ACalanolide BCalanolide D Inocalophyllin AInocalophyllin BTamanolideTamanolide DTamanolide P Coumarin derivatives identified in Tamanu oil. Inophyllum serie Calanolide serie Inocalophyllin serie Tamanolide serie Epicalanolide C12-oxocalanolide A Tamanolide is a new serie of coumarin derivatives Elastase inhibiting activity. Structure-activity relationship. Calophyllolide is the most active compound (IC 50 = 8.4 µM) Phenyl C-4 substituent, methoxyl C-8b and tigloyl C-12a groups appears to be structural requirements for elastase inhibition by coumarin derivatives