Role of LC/UV/MS2 in the search for antiplasmodial Polycyclic Polyprenylated Acylphloroglucinols

Malaria still remains an important parasitic disease in developing countries. For example, new cases of resistance appear in South America, particularly in French Guiana [1]. A systematic biological evaluation on Plasmodium falciparum of plant extracts collected in this country has allowed to select two Clusiaceae species, Moronobea coccinea Aubl. and Symphonia sp. This family is known to be a rich source of polycyclic polyprenylated acylphloroglucinols (PPAPs) with a large spectre of biological activity [2]. However, to our knowledge, only Guttiferone A has been tested for its antiplasmodial activity [3]. Phytochemical investigation of the trunk latex of Moronobea coccinea led to the isolation of twelve PPAPs. All compounds share the same type B phloroglucinol skeleton [4] and could be delineated by the position of their prenyl side chain and the presence of a tetrahydropyrane ring. Biological assay on Plasmodium falciparum chloroquin resistant strain (FCB1) showed IC₅₀ from 3.3µM to 37.2µM. PPAPs with a tetrahydropyrane ring present the best antiplasmodial activity. Analysis of LC/UV/MS² spectra of isolated PPAPs suggested some characteristics fragments for this chemical series. This hyphenated technique has been successfully applied on a bioactive extract from Symphonia sp, a close related species, and led to the isolation of eight new antiplasmodial PPAPs. This method constitutes an interesting tool for the structure prediction of type B PPAPs derivatives.

Acknowledgements: This works was supported by an ICSN-CNRS grant to one of us (G.M.).

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