Bruno Figadère

Substituted quinolines induce inhibition of proliferation of HTLV-1 infected cells.

Several quinolines were synthesized and evaluated against HTLV-1 infected cells. Some of them were able to inhibit HTLV-1 cell-growth at 10 microM. Some structure-activity relationships were observed.

Antiprotozoal 6-Substituted-5,6-Dihydro-a-Pyrones from Raimondia CF. Monoica

Dichloromethane extracts of both the roots and the leaves of Raimondia cf. monoica showed in vitro antiplasmodial and leishmanicidal activities against Plasmodium falciparum and Leishmania panamensis, respectively. Three 6-substituted 5,6-dihydro-2H-pyran-2-ones were isolated. (1) and (2) were identified as (6S)-(5′-oxohepten-1′E,3′E-dienyl)-5,6-dihydro-2H-pyran-2-one (1) and (6R)-(5′-oxohepten-1′Z,3′E-dienyl)-5,6-dihydro-2H-pyran-2-one (2), respectively. (-)-Argentilactone (3) was also isolated. The structure of the new compound (1) was determined by spectroscopic methods; additional spectroscopic data for (2) are reported for the first time.

Four New Acetogenins from the Seeds of Annona reticulata 1

Abstract Four new acetogenins, dieporeticanin-1 and -2 (1 and 2 respectively), dieporeticenin (3) and trieporeticanin (4) were isolated, with the known diepomuricanin (5), from the seeds of the vietnamese Annonaceae, Annona reticulata. Their structures were elucidated on the basis of the spectral data. Biomimetic hemi-synthesis of reticulatacin (6), solamin (7) from dieporeticanin-1 (1), diepomuricanin (5) respectively, sustains the key role of such natural precursors in the biogenesis of acetogenins.

Acetogenins of annonaceae. Part 86: synthesis of a highly functionalized precursor of (−)-4-deoxygigantecin, an annonaceous acetogenin

A highly functionalized precursor of (−)-4-deoxygigantecin possessing six stereogenic centers has been prepared in 14 steps from tridecanal. The key steps are (i) enantioselective aldolization, (ii) diastereoselective C-glycosylation and (iii) diastereoselective aldolization reactions, all of them using 2-trimethylsilyloxyfuran as nucleophile. This strategy would allow us to prepare squamostatin D as well, another acetogenin of Annonaceae possessing two nonadjacent tetrahydrofuran rings and a closely related tetrahydrofuran pattern.

Tripoxyrollin, a New Epoxy Acetogenin from the Seeds of Rollinia membranacea 1

Abstract A new epoxy acetogenin, tripoxyrollin (1), has been isolated from the seeds of the Colombian Annonaceae, Rollinia membranacea. Its structure was elucidated on the basis of spectral data. Biomimetic synthesis of isodesacetyluvaricin (2) from tripoxyrollin (1) suggests its key role in the biogenesis of the adjacent bis-tetrahydrofuran acetogenins.

SYNTHESIS AND LEISHMANICIDAL ACTIVITY OF NEW BIS-ALKYLQUINOLINES

ABSTRACT Bis-alkylquinolines 1-6 were synthetized via Williamson reaction between 8-hydroxyquinaldine with different 1,ω-dihaloalkanes. Structures of all the products were elucidated by spectroscopic analysis. Cytotoxic and antileishmanial activities of synthesized compounds were determinated on U-937 cells and L. (V) panamensis amastigotes, respectively. Compound 5 , 1,9-bis[(2-methylquinolin-8-yl)oxy]nonane , was the most selective against axenic and intracellular amastigotes (EC 50 = 11.3 and 22.6, μg/mL), with selectivity indices greater than 17.7 and 8.8, respectively; which makes this compound promising for the developing of new leishmanicidal drugs. Keywords: Leishmania, antiprotozoal, quinoline. e-mail: wcardona@matematicas.udea.edu.co INTRODUCTION Leishmaniasis is one of the world’s most neglected diseases, affecting largely the poorest of the poor, mainly in developing countries; 350 million people are considered at risk of contracting leishmaniasis, and around 2 million new cases occur yearly

ANTILEISHMANIAL ACTIVITY OF A FORMULATION OF 2-N-PROPYLQUINOLINE BY ORAL ROUTE IN MICE MODEL

2-n-propylquinoline is presently a drug-candidate for the treatment of visceral leishmaniosis in pre-clinical development. As this compound is in an oily state, it needs to be formulated and the objectives of this study are: to prepare a formulation; to demonstrate that the new salted formulation did not alter the activity of the active ingredient; and finally, that this activity was quite good compared to the reference oral drug, miltefosine. Therefore, a 2-n-propylquinoline formulation, as camphorsulfonic salt, was prepared and characterised. On the Leishmania donovani / Balb/c mice model, a treatment by oral route at 60 μmoles/kg/day for ten consecutive days with this formulation was compared to 2-n-propylquinoline alone and to miltefosine, the oral reference drug. The salt formulation did not alter the activity of the 2-n-propylquinoline. The formulation reduced the parasite burden of 76% compared to 89% for miltefosine (not significant). The characteristics of this formulation results in a suitable drugability of 2-n-propylquinoline for further studies.