Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities.

The development of new and effective antimicrobial compounds is urgent due to the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules, but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring.

Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus.

Background: Mycobacterium abscessus, a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic fibrosis (CF). Due to its intrinsic polyresistance to a wide range of antibiotics, most treatments for M. abscessus pulmonary infections are poorly effective.

Evaluation of the Efficiency of Random and Diblock Methacrylate-Based Amphiphilic Cationic Polymers against Major Bacterial Pathogens Associated with Cystic Fibrosis.

Cystic fibrosis (CF) is associated with repeated lung bacterial infection, mainly by , , and , all known to be or becoming resistant to several antibiotics, often leading to therapeutic failure and death. In this context, antimicrobial peptides and antimicrobial polymers active against resistant strains and less prompt to cause resistance, appear as a good alternative to conventional antibiotics. In the present study, methacrylate-based copolymers obtained by radical chemistry were evaluated against CF-associated bacterial strains.

Classification and Nomenclature of Metacaspases and Paracaspases: No More Confusion with Caspases.

Metacaspases and paracaspases are proteases that were first identified as containing a caspase-like structural fold (Uren et al., 2000). Like caspases, meta- and paracaspases are multifunctional proteins regulating diverse biological phenomena, such as aging, immunity, proteostasis and programmed cell death.

Cell death in Leishmania.

Leishmaniases still represent a global scourge and new therapeutic tools are necessary to replace the current expensive, difficult to administer treatments that induce numerous adverse effects and for which resistance is increasingly worrying. In this context, the particularly original organization of the Leishmania parasite in comparison to higher eukaryotes is a great advantage. It allows for the development of new, very specific, and thus non-cytotoxic treatments.

A novel hydrolase with a pro-death activity from the protozoan parasite .

Apoptosis is a cell death process generally described as involving a cascade of caspase activation, death receptors and/or pro- and antiapoptotic molecules from the BcL-2 family. But about 20 years ago, a caspase-independent apoptotic pathway has been described. Regarding this pathway, we can learn a lot from parasites.

A potential acetyltransferase involved in Leishmania major metacaspase-dependent cell death.

Background: Currently, there is no satisfactory treatment for leishmaniases, owing to the cost, mode of administration, side effects and to the increasing emergence of drug resistance. As a consequence, the proteins involved in Leishmania apoptosis seem a target of choice for the development of new therapeutic tools against these neglected tropical diseases. Indeed, Leishmania cell death, while phenotypically similar to mammalian apoptosis, is very peculiar, involving no homologue of the key mammalian apoptotic proteins such as caspases and death receptors.

(De)glutamylation and cell death in Leishmania parasites.

Trypanosomatids are flagellated protozoan parasites that are very unusual in terms of cytoskeleton organization but also in terms of cell death. Most of the Trypanosomatid cytoskeleton consists of microtubules, forming different substructures including a subpellicular corset. Oddly, the actin network appears structurally and functionally different from other eukaryotic actins.

Nongenotoxic 3-Nitroimidazo[1,2-]pyridines Are NTR1 Substrates That Display Potent Antileishmanial Activity.

Twenty nine original 3-nitroimidazo[1,2-]pyridine derivatives, bearing a phenylthio (or benzylthio) moiety at position 8 of the scaffold, were synthesized. evaluation highlighted compound as an antiparasitic hit molecule displaying low cytotoxicity for the human HepG2 cell line (CC > 100 μM) alongside good antileishmanial activities (IC = 1-2.1 μM) against , , and ; and good antitrypanosomal activities (IC = 1.

Temporal analysis of the autophagic and apoptotic phenotypes in parasites.

The leishmaniases are worldwide neglected tropical diseases caused by parasitic protozoa of the genus. Different stimuli induce cell death, but the proteins involved remain poorly understood. Furthermore, confusion often appears between cell death and the cell survival process autophagy, whose phenotype is not clearly defined.

Calcein+/PI- as an early apoptotic feature in Leishmania.

Although leishmaniases are responsible for high morbidity and mortality all over the world, no really satisfying treatment exists. Furthermore, the corresponding parasite Leishmania undergoes a very characteristic form of programmed cell death. Indeed, different stimuli can induce morphological and biochemical apoptotic-like features.

Characterisation of polyglutamylases in trypanosomatids.

Microtubules are subject to post-translational modifications, which are thought to have crucial roles in the function of complex microtubule-based organelles. Among these, polyglutamylation was relatively recently discovered, and was related to centrosome stability, axonemal maintenance and mobility, and neurite outgrowth. In trypanosomatids, parasitic protozoa where microtubules constitute the essential component of the cytoskeleton, the function of polyglutamylated microtubules is unknown.

Targeting the human parasite Leishmania donovani: discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series.

We report herein the discovery of antileishmanial molecules based on the imidazo[1,2-a]pyridine ring. In vitro screenings of imidazopyridines belonging to our chemical library, toward the promastigotes stage of Leishmania donovani, J774A.1 murine and HepG2 human cells, permitted to identify three selective hit-compounds (12, 20 and 28).

A new, rapid and sensitive bioluminescence assay for drug screening on Leishmania.

We validated a new method, based on luciferine/luciferase bioluminescence, for drug screening on promastigotes of different Leishmania species. Results obtained with this new, rapid, reproducible, and reliable method are in good accordance with results obtained by the conventional MTT assay. This bioluminescence assay has a lower detection limit.

Discovery of a new antileishmanial hit in 8-nitroquinoline series.

A series of nitrated 2-substituted-quinolines was synthesized and evaluated in vitro toward Leishmania donovani promastigotes. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Thus, a very promising antileishmanial hit molecule was identified (compound 21), displaying an IC(50) value of 6.

Microtubule-severing proteins are involved in flagellar length control and mitosis in Trypanosomatids.

Microtubules are key players in the biology of Trypanosomatid parasites, not only as classical components of the mitotic spindle, microtubule-organizing centres and flagellum but also as the essential constituent of the cytoskeleton. Their length dynamics are regulated by, among others, microtubule-severing proteins. Four and six genes encoding microtubule-severing proteins can be found bioinformatically in the Leishmania major and Trypanosoma brucei genome respectively.