La protéine farnésyltransférase (FTase) est une métalloenzyme à zinc catalysant le transfert d’une chaîne farnésyle provenant du pyrophosphate de farnésyle (FPP) sur le résidu cystéine de certaines protéines possédant un motif CaaX C-terminal où C est la cystéine farnésylée, a est un acide aminé aliphatique et X est Ser, Ala, Gln ou Met. Une fois additionné, le groupement farnésyle fait office de point d’ancrage rendant possible la fixation des protéines à la membrane cellulaire et de guide moléculaire facilitant la liaison de ces protéines prénylées à d’autres protéines. D’abord étudiée en oncologie, la FTase constitue aujourd’hui une cible potentielle pour la thérapie antiparasitaire qui manque cruellement de médicaments suite à l’apparition de phénomènes de résistance. La nécessité d’améliorer les thérapies existantes ouvre la voie de recherches innovantes pour trouver de nouvelles molécules bioactives.Lors de ces travaux de thèse, les deux stratégies de recherche pratiquées en chimie médicinale ont été utilisées.La première approche a consisté à synthétiser des analogues bisubstrats 1,2,3-triazoles pouvant se lier à la fois sur le site de liaison de la protéine et sur celui du FPP. Cette approche rationnelle a aussi permis d’ébaucher une synthèse monotope de triazoles 1,5-disubstitués à partir d’amines primaires. L’approche par criblage constitue la deuxième méthode de recherche de nouveaux inhibiteurs. Dans ce contexte, la chimiothèque de l’ICSN a été criblée et deux composés de type 3-arylthiophène ont révélé de bonnes activités et une structure originale dans l’inhibition de la FTase. Ainsi, des travaux de relations structure-activité ont été réalisés pour moduler les différentes positions du thiophène et la nature de l’hétérocycle central.Ce travail nous a permis d’élaborer une librairie de plus d’une centaine de composés. L’évaluation biologique de ces analogues sur FTases isolées humaine et de T. brucei et sur parasites T. brucei et P. falciparum a révélé des molécules particulièrement intéressantes et prometteuses. / Protein farnesyltransferase (FTase) is a zinc metalloenzyme which catalyzes the transfer of a farnesyl chain from farnesyl pyrophosphate (FPP) to the cysteine residue of some proteins possessing a C-terminal CaaX moiety where C is the farnesylated cysteine, a is an aliphatic amino-acid and X is Ser, Ala, Gln or Met. Once attached, the farnesyl group serves as anchors for fixing proteins to cell membrane and as molecular handles for facilitating binding of these prenylated proteins to other proteins.First studied in oncology, FTase constitutes nowadays a potential target for antiparasitic therapies, where drugs are missing due to the appearance of resistance phenomena. The necessity to improve the existing therapies paves the way of innovating researches to find new bioactive molecules.During this Ph.D work, two strategies of research used in medicinal chemistry were performed.The first approach consisted in the synthesis of bisubstrate analogues with a 1,2,3-triazole core deviced to tie up both to the protein and the FPP binding sites. This rational approach also allowed to draft a one-pot synthesis of 1,5-disubstituted triazoles from primary amines.The screening approach was the second strategy to search for new inhibitors. For this purpose, ICSN chemical library was screened and two 3-arylthiophene compounds disclosed good activities and an original scaffold for FTase inhibition. Therefore, a structure-activity relationship study was carried out to modulate the different positions of the thiophene and the nature of the central heterocycle.This work allowed us to create a above-hundred-molecule library. The biological evaluation of these analogues on human and T. brucei isolated FTase and on T. brucei and P. falciparum parasites revealed particularly interesting and promising molecules.

Monolayer two-dimensional (2D) materials have been regarded as a hot topic in the fields of condensed matter physics, materials science, and chemistry due to their unique physical, chemical, and electronic properties. However, the research on the preparation method and properties understanding of the 2D monolayer are inadequate. In this dissertation, taking 2D nickel-iron layered double hydroxides (NiFe LDHs) and molybdenum disulfide (MoS2) as examples, the practicability of the direct synthesis of NiFe LDHs monolayer and the thermal enhancement catalytic performance of 2D MoS2 monolayer (MoS2 ML) are discussed. First, a one-pot synthetic strategy (bottom-up method) is presented to synthesize 2D NiFe-based LDHs monolayers, including NiFe, Co-, Ru-, doped, and Au-modified NiFe LDHs. The prerequisite and universality of this strategy are investigated and confirmed. The features of LDHs are characterized by advanced technologies. The obtained LDH bulks own a large interlayer spacing up to 8.2 Å, which can be facilely exfoliated into monolayers in water by hand-shaking within 10 s. As a result, the as-prepared NiFe-based LDH monolayers display a good electrocatalytic oxygen evolution reaction (OER) performance. This facile strategy paves the way for designing easily exfoliated LDHs for highly active catalysts and energy conversion devices based on other monolayer LDHs. Second, with gold-modified tape, 2D MoS2 ML is exfoliated from the bulk crystal through a micromechanical exfoliation method (top-down strategy). The thermal effects of MoS2 ML are confirmed by Raman and photoluminescence (PL) spectra. Moreover, an on-chip MoS2 ML hydrogen evolution reaction (HER) reactor is designed and fabricated. The thermal effects generate efficient electron transfer in the MoS2 ML and at the electrolyte-catalyst (MoS2 ML) interface, leading to an enhanced HER performance. Compared to the results obtained at room temperature, the MoS2 ML shows a direct thermal enhanced HER performance at higher temperatures. In summary, the findings and understandings, the direct synthesis and direct thermal enhancement catalytic performance, of 2D monolayers offer a guideline for synthesizing and catalyst application of other 2D monolayers.