FERNANDO CORTES - Academia.edu (original) (raw)

Papers by FERNANDO CORTES

Plant Ecology and Evolution, 2012

Planta Medica, 2007

The kavapyrone (+)-(7 R,8 S)-epoxy-5,6-didehydrokavain (1) and the chalcone flavokavain B (2) wer... more The kavapyrone (+)-(7 R,8 S)-epoxy-5,6-didehydrokavain (1) and the chalcone flavokavain B (2) were isolated from Piper rusbyi as the bioactive components by bioassay-guided fractionation, using an in vitro assay against promastigote forms of three Leishmania strains. In addition, the new kavapyrone, (7 R,8 R/7 S,8 S)-dihydroxy-5,6-didehydrokavain (3), which is very likely an artifact, and four known compounds (4-7) were isolated. Their structures were elucidated on the basis of spectral analysis, and the absolute configurations of compounds 1 and 3 were established by CD studies and the modified Mosher ester procedure, respectively. All compounds were evaluated for in vitro leishmanicidal activity. The most active compounds 1 (IC50=81.9 microM) and 2 (IC50=11.2 microM) were also evaluated in vivo against a New World strain of cutaneous leishmaniasis, and the results showed the efficacy of 2 at a dose of 5 mg/kg/day. Compounds 1 and 3 were also assayed as reversal agents against a multidrug-resistant Leishmania tropica line, but were found to be inactive.

Journal of Medicinal Chemistry, 2004

Journal of Medicinal Chemistry, 2001

Parasite resistance to drugs has emerged as a major problem in current medicine, and therefore, t... more Parasite resistance to drugs has emerged as a major problem in current medicine, and therefore, there is great clinical interest in developing compounds that overcome these resistances. In an intensive study of South American medicinal plants, herein we report the isolation, structure elucidation, and biological activity of dihydro-beta-agarofuran sesquiterpenes from the roots of Maytenus magellanica (1-14) and M. chubutensis (14-17). This type of natural products may be considered as privileged structures. The structures of 10 new compounds, 1, 3, 6-9, and12-15, were determined by means of (1)H and (13)C NMR spectroscopic studies, including homonuclear (COSY and ROESY) and heteronuclear correlation experiments (HMQC and HMBC). The absolute configurations of eight hetero- and homochromophoric compounds, 1, 3,6-9, 12, and 13, were determined by means of CD studies. Fourteen compounds, 1-3 and 6-16, have been tested on a multidrug-resistant Leishmania tropica line overexpressing a P-glycoprotein-like transporter to determine their ability to revert the resistance phenotype and to modulate intracellular drug accumulation. From this series, 1, 2, 3, 14, and 15 showed potent activity, 1 being the most active compound. The structure-activity relationships of the different compounds are discussed.

Biodiversity and Conservation, 2013

We investigated the effect of woody species' encroachment on plant diversity changes with regard ... more We investigated the effect of woody species' encroachment on plant diversity changes with regard to vascular plants and bryophytes in traditional olive groves of the Maremma Regional Park (Tuscany, Italy) and assessed cross-taxon correlation between these two taxa. We classified the olive groves into four land use types, representing different successional stages. To describe the evenness of species distribution within a community, we plotted rank-abundance diagrams for each taxon and each land use type. The relationship between the number and cover of vascular plants, therophytes, bryophytes, colonists and phanerophytes in each plot was examined using linear regression. The effects of land use type on vascular plant and bryophyte richness and assemblages were assessed by permutational uni-and multivariate analysis of variance. The congruence in species composition between the two taxa was evaluated using Procrustes analysis. The number of vascular plants, bryophytes and therophytes decreased linearly with increased phanerophyte species cover. The number of species belonging to Thero-Brachypodietea progressively decreased throughout succession. Rank-abundance diagrams and multivariate analysis showed differences between the land use types, which were statistically significant for vascular plants between the traditional olive groves and the other land use types, and for bryophytes between the traditional olive groves and woodlands. PROTEST analysis and NMDS graphs showed a correlation between vascular plant and bryophyte communities. The results suggested that conservation measures are needed in the study area in order to ensure both the maintenance of traditional olive groves of conservation interest and high levels of environmental heterogeneity.

Biochemical and Biophysical Research Communications, 2005

P-glycoprotein (Pgp) transporters play an important role in multidrug resistance in eukaryotic ce... more P-glycoprotein (Pgp) transporters play an important role in multidrug resistance in eukaryotic cells and in protozoan parasites such as Leishmania. To search for new reversal agents of the Leishmania tropica Pgp, we developed a screening assay using the Baculovirus-insect cell expression system. We demonstrated a MgATP-dependent, vanadate-sensitive transport of Hoechst 33342 in membrane preparations of Sf9 insect cells expressing Pgp. We have found that dihydro-b-agarofuran sesquiterpenes from Maytenus cuzcoina inhibited Hoechst 33342 transport that correlates with their reversal effect in a multidrug-resistant L. tropica line overexpressing Pgp. The results suggest that Sf9 cell membrane Hoechst 33342 transport system represents an efficient tool for examining the interactions of Leishmania Pgp with pharmacological agents.

Antimicrobial Agents and Chemotherapy, 2006

Miltefosine (hexadecylphosphocholine) is the first orally active drug approved for the treatment ... more Miltefosine (hexadecylphosphocholine) is the first orally active drug approved for the treatment of leishmaniasis. We have previously shown the involvement of LtrMDR1, a P-glycoprotein-like transporter belonging to the ATP-binding cassette superfamily, in miltefosine resistance in Leishmania. Here we show that overexpression of LtrMDR1 increases miltefosine efflux, leading to a decrease in drug accumulation in the parasites. Although LtrMDR1 modulation might be an efficient way to overcome this resistance, a main drawback associated with the use of P-glycoprotein inhibitors is related to their intrinsic toxicity. In order to diminish possible side effects, we have combined suboptimal doses of modulators targeting both the cytosolic and transmembrane domains of LtrMDR1. Preliminary structure-activity relationships have allowed us to design a new and potent flavonoid derivative with high affinity for the cytosolic nucleotide-binding domains. As modulators directed to the transmembrane...

Current Pharmaceutical Design, 2005

Leishmaniasis is the most important emerging and uncontrolled infectious disease and the second c... more Leishmaniasis is the most important emerging and uncontrolled infectious disease and the second cause of death among parasitic diseases, after Malaria. One of the main problems concerning the control of infectious diseases is the increased resistance to usual drugs. Overexpression of P-glycoprotein (Pgp)-like transporters represents a very efficient mechanism to reduce the intracellular accumulation of drugs in cancer cells and parasitic protozoans, thus conferring a multidrug resistance (MDR) phenotype. Pgps are active pumps belonging to the ATP-binding cassette (ABC) superfamily of proteins. The inhibition of the activity of these proteins represents an interesting way to control drug resistance both in cancer and in infectious diseases. Most conventional mammalian Pgp-MDR modulators are ineffective in the modulation of Pgp activity in the protozoan parasite Leishmania. Consequently, there is a necessity to find effective modulators of Pgp-MDR for protozoan parasites. In this review we describe a rational strategy developed to find specific Pgp-MDR modulators in Leishmania, using natural and semisynthetic dihydro-β-agarofuran sesquiterpenes from Celastraceae plants. A series of these compounds have been tested on a MDR Leishmania tropica line overexpressing a Pgp transporter to determine their ability to revert the resistance phenotype and to modulate intracellular drug accumulation. Almost all of these natural compounds showed potent reversal activity with different degrees of selectivity and a significant low toxicity. The three-dimensional quantitative structure-activity relationship using the comparative molecular similarity indices analysis (CoMSIA), was employed to characterize the requirements of these sesquiterpenes as modulators at Pgp-like transporter in Leishmania.

Planta Medica, 2011

A new bicyclic diterpene with a labdane skeleton, 7-oxo-labd-8en-15-ol (1), along with two known ... more A new bicyclic diterpene with a labdane skeleton, 7-oxo-labd-8en-15-ol (1), along with two known diterpenes and ten flavonoids were isolated from the leaves of Aeonium lindleyi (Crassulaceae). Their structures were elucidated on the basis of spectroscopic data, including 1D and 2D NMR experiments, and comparison with spectroscopic data reported in the literature. Labdan-8α,15-diol (2) and labd-8(17)-en-3β,15-diol (3) showed leishmanicidal activity against Leishmania tropica (IC 50 = 77.0 µM) and Leishmania braziliensis (IC 50 = 68.0 µM) similar to ketoconazole used as positive control. 5,3′-Dihydroxy-3,7,4′,5′-tetramethoxyflavone (8) and combretol (9) showed moderate activity (growth inhibition 87.3 and 73.0 %, respectively, at 50 µM) against a multidrug-resistant L. tropica line.

Bioorganic & Medicinal Chemistry, 2008

Two new sesquiterpenes (1-2) and one new lupane triterpene (3) have been isolated from the roots ... more Two new sesquiterpenes (1-2) and one new lupane triterpene (3) have been isolated from the roots of Maytenus apurimacensis. The novel beta-dihydroagarofurans are the first sesquiterpenes with a basic polyhydroxy skeleton of 15-deoxyalatol and 4,15-dideoxyalatol that show high MDR reversing activity in the protozoan parasite Leishmania tropica.