Inactivation of Malaria Parasites in Blood: PDT vs Inhibition of Hemozoin Formation

Malaria causes hundreds of thousands of human deaths every year, and the World Health Assembly has made it a priority. To help eliminate this disease, there is a pressing need for the development and implementation of new strategies to improve the prevention and treatment, due in part to antimalarial drug resistances. This chapter focuses on two strategies to inactivate the malaria parasite in blood, which are photodynamic therapy (PDT) and inhibition of hemozoin formation. The PDT strategy permits either a control of the proliferation of mosquito larvae to develop some photolarvicides for the prevention or a photoinactivation of the malaria parasite in red blood cells (RBCs) to minimize infection transmission by transfusion. The inhibition of hemozoin formation strategy is used for the development of new antimalarial drug by understanding its formation mechanism

Utilisation de bases pyrimidiques pour l'élaboration d'analogues d'oligonucléosides ou de la chlorméthine

Nous décrivons la synthèse d analogues d oligonucléosides et de la chlorméthine à partir de bases pyrimidiques. Dans une première partie, la synthèse des analogues de dinucléosides reliés par une chaîne carbonée insaturée entre les positions 3 , 3 et 5 à partir de la thymidine portant des groupements allyles est décrite. Un analogue de trinucléoside présentant la même chaîne carbonée entre les positions 3 et 3 a également été synthétisé. L étape clé de ces synthèses utilise la réaction de métathèse des oléfines. Une étude de cette réaction par activation micro-onde a été réalisée. Dans une seconde partie, nous présentons la synthèse d agents alkylants à partir de bases pyrimidiques, suivie de leur évaluation biologique. L étape clé de ces synthèses est la fixation d une ou deux chaînes chloroéthyle sur la base pyrimidique, dont une optimisation a été réalisée par activation micro-onde. Certains analogues ont été glycosylés afin d augmenter leur index thérapeutique. Tous les produits synthétisés ont été caractérisés par différentes méthodes spectroscopiques. L activité anticancéreuse de plusieurs agents alkylants synthétisés donne des résultats préliminaires très encourageants.The synthesis of oligonucleoside and chlormethine analogues from pyrimidic bases is described. The first part presents the synthesis of dinucleoside analogues linked by an unsatured hydrocarbon chain between positions 3 , 3 and 5 from thymidine with an allyle group. One trinucleoside analogue containing the same hydrocarbon chain between the positions 3 and 3 is also synthesized. The key step of these syntheses is the use of olefin metathesis reaction. We performed a study of microwave-activated cross metathesis. In the second part, we present the synthesis and the biological activity of alkylating agents from pyrimidic bases. The key step of these syntheses is the fixation of one or two chloroethyle chains on pyrimidic base. An optimization of this step is obtained by microwave activation. Some analogues have been glycosylated to increase their therapeutic index. All synthesized products have been characterized by spectroscopic analyses. The antitumoral activity of several synthesized alkylating agents gave very interesting preliminary results.LIMOGES-BU Sciences (870852109) / SudocSudocFranceF

Iterative reconstruction of thermally induced phase distortion in a Nd 3+ :YVO 4 laser

International audienceThe thermal distortions in a continuous-wave end-pumped Nd:YVO 4 laser are experimentally investigated by use of an external TEM 00 probe beam (TEM standing for transverse electric magnetic). After a round-trip of this probe through the active medium, three irradiance profiles are recorded along its propagation axis. The distorted phase pattern of this probe beam is then reconstructed from these profiles by means of a Gerchberg-Saxton-like iterative algorithm. To identify the contribution of each kind of aberration in the phase profile, we have computed a Zernike polynomial expansion, and have shown that the main terms constituting the aberration are (in order) defocusing (optical path difference (OPD) 0.7 λ FWHM (full width at half-maximum)), spherical aberration (OPD 0.3 λ FWHM), and first-order astigmatism (OPD of ±0.14 λ p FWHM). Moreover, all higher-order terms result in a significant phase peak (λ/4 FWHM over 400 µm)

Dual frequency tunable cw Nd:YAG laser

International audienceA three-mirror laser, with very dierent spacings between the mirrors is studied numerically and experimentally. Two laser lines are emitted with a beat frequency in the tenths of GHz and a very ®ne tunability. Ó 2001 Published by Elsevier Science B.V

Rapid Access to Ironomycin Derivatives by Click Chemistry

International audienceSalinomycin, a natural carboxylic polyether ionophore, shows a very interesting spectrum of biological activities, including selective toxicity toward cancer stem cells (CSCs). Recently, we have developed a C20-propargylamine derivative of salinomycin (ironomycin) that exhibits more potent activity in vivo and greater selectivity against breast CSCs compared to the parent natural product. Since ironomycin contains a terminal alkyne motif, it stands out as being an ideal candidate for further functionalization. Using copper-catalyzed azide-alkyne cycloaddition (CuAAC), we synthesized a series of 1,2,3-triazole analogs of ironomycin in good overall yields. The in vitro screening of these derivatives against a well-established model of breast CSCs (HMLER CD24low/CD44high) and its corresponding epithelial counterpart (HMLER CD24high/CD44low) revealed four new products characterized by higher potency and improved selectivity toward CSCs compared to the reference compound ironomycin. The present study highlights the therapeutic potential of a new class of semisynthetic salinomycin derivatives for targeting selectively the CSC niche and highlights ironomycin as a promising starting material for the development of new anticancer drug candidates

Amphiphilic photosensitive dextran-g-poly(o-nitrobenzyl acrylate) glycopolymers

International audienceAmong all photosensitive monomers reported in the literature, o-nitrobenzyl acrylate (NBA) was selected in this present study. Two strategies were compared to produce azido-terminated poly(o-nitrobenzyl acrylate) (PNBA) using controlled Single Electron Transfer-Living Radical Polymerization (SET-LRP). In a parallel way, dextran (Dex) was modified by the introduction of several alkynyl-terminated hydrophobic chains. Finally, an Huisgen-type Copper (I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) click-chemistry was carried out to produce amphiphilic Dex-g-PNBA glycopolymers with different number and length of PNBA grafts. 2D DOSY H-1 NMR was used to prove the formation of such glycopolymers. Preliminary study on Dex-g-PNBA self-assembly was done by measuring the critical water content (CWC) above which Dex-g-PNBA started to auto-organize themselves to produce nano-objects. Finally, under UV irradiation, PNBA grafts turn into poly(acrylic acid) ones giving light-sensitive properties to such amphiphilic Dex-g-PNBA. Such properties were evaluated and compared with those of PNBA

Temporal statistics of the light emitted by a bi-axial laser resonator

International audiencePower spectral density of the light emitted by a bi-axial CW Nd:YAG, diode-pumped, laser is investigated. We show that the beams diffracted by a slit with adjustable width, placed inside the cavity, against the folding mirror, can modify the temporal autocorrelation function and spectral behaviour of the laser emission. In a second experiment, carried out with a pulsed Nd:YAG laser, we show that the temporal profile itself depends on the diffraction by the slit placed inside the resonator

Solvent-controlled regioselective protection of 5'-O-protected thymidine.

International audienceThis paper describes an efficient procedure for selective 3'-O- or 3-N-protection of 5'-O-tert-butyldimethylsilylthymidine, depending on the use of aprotic polar solvents with low or high dielectric constant, respectively. These syntheses were activated by either ultrasound or microwaves. Several alkyl bromides offer a convenient route to prepare 3'-O- or 3-N-protected and functionalized thymidine derivatives

Photomolecular beacon ciblant LRP-1, activables par les MMPs pour traiter le glioblastome par thérapie photodynamique.

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