Steady electrocorticogram characteristics predict specific stress-induced behavioral phenotypes.

Introduction: Depending on the individual, exposure to an intense stressor may, or may not, lead to a stress-induced pathology. Predicting the physiopathological evolution in an individual is therefore an important challenge, at least for prevention. In this context, we developed an ethological model of simulated predator exposure in rats: we call this the multisensorial stress model (MSS).

Synthesis and study of new siderophore analog-ciprofloxacin conjugates with antibiotic activities against Pseudomonas aeruginosa and Burkholderia spp.

Antibacterial resistance is a healthcare burden. Among Gram-negative bacteria, Pseudomonas aeruginosa belongs to the first list of antibiotic-resistant "priority pathogens" described by the World Health Organization. Formerly Pseudomonas pseudomallei, Burkholderia pseudomallei, responsible for melioidosis, is considered as a potential bioterrorist weapon by the Centers of Diseases Control and Prevention.

Toxicokinetics of plasmatic VX in a swine model: comparison of a simple enzymatic titration method with a mass spectrometry method.

Recent events have shown that organophosphorus nerve agents (OPNAs) are a serious threat. Cholinesterase inhibition by OPNAs results in acetylcholine accumulation, a cholinergic crisis leading to death if untreated. Efficacy assessment of new medical countermeasures against OPNAs relies on translational animal models.

Design, synthesis, and characterization of novel aminoalcohol quinolines with strong in vitro antimalarial activity.

Malaria is the fifth most lethal parasitic infections in the world. Herein, five new series of aminoalcohol quinolines including fifty-two compounds were designed, synthesized and evaluated in vitro against Pf3D7 and PfW2 strains. Among them, fourteen displayed IC values below or near of 50.

Role of Anopheles stephensi Mosquitoes in Malaria Outbreak, Djibouti, 2019.

Anopheles stephensi mosquitoes share urban breeding sites with Aedes aegypti and Culex quinquefasciatus mosquitoes in the Republic of Djibouti. We present evidence that A. stephensi mosquitoes might be responsible for an increase in malaria incidence in this country.

A Validated Volumetric Absorptive Microsampling-Liquid Chromatography Tandem Mass Spectrometry Method to Quantify Doxycycline Levels in Urine: An Application to Monitor the Malaria Chemoprophylaxis Compliance.

Because of logistics and cost constraints, monitoring of the compliance to antimalarial chemoprophylaxis by the quantitation of drugs in biological samples is not a simple operation on the field. Indeed, analytical devices are fragile to transport and must be used in a perfectly controlled environment. This is also the case for reagents and supplies, and the waste management is constraining.

Study of Iron Piperazine-Based Chelators as Potential Siderophore Mimetics.

Gram-negative bacteria's resistance such as and the group to conventional antibiotics leads to therapeutic failure. Use of siderophores as Trojan horses to internalize antibacterial agents or toxic metals within bacteria is a promising strategy to overcome resistance phenomenon. To combat the sp, we have synthesized and studied two piperazine-based siderophore mimetics carrying either catecholate moieties () or hydroxypyridinone groups () as iron chelators.

Design and synthesis of simplified speciophylline analogues and β-carbolines as active molecules against Plasmodium falciparum.

A structure-activity relationship study of active molecules against chloroquine-resistant Plasmodium falciparum K1 strain is reported. Structurally simplified analogues of antiplasmodial active alkaloids presented similar levels of activity as their corresponding natural products extracted from Guiera senegalensis and Mitragyna inermis with IC values on chloroquine-resistant P. falciparum K1 strain of up to 10.

Superior efficacy of HI-6 dimethanesulfonate over pralidoxime methylsulfate against Russian VX poisoning in cynomolgus monkeys (Macaca fascicularis).

Organophosphorus nerve agents still represent a serious risk to human health. In the French armed forces, the current emergency treatment against OP intoxications is a fully licensed wet-dry dual-chambered autoinjector (Ineurope ®), that contains pralidoxime methylsulfate (2-PAM) to reactivate inhibited acetylcholinesterase (AChE), atropine sulfate (AS) and avizafone chlorhydrate (AVZ). While this treatment is effective against several of the known nerve agents, it shows little efficacy against the Russian VX (VR), one of the most toxic compounds.

Synthesis and Antimalarial Activity of New Enantiopure Aminoalcoholpyrrolo[ 1,2-a]quinoxalines.

Background: We prepared a novel series of enantiopure mefloquine analogues with pyrrolo[ 1,2-a]quinoxaline core in order to fight Plasmodium falciparum resistant strain.

Objectives: To observe the influence of pyrrolo[1,2-a]quinoxaline core versus quinoline core on the antimalarial activity.

Method: Four enantiopure aminoalcoholpyrrolo[1,2-a]quinoxalines 2 were synthetized via Sharpless asymmetric dihydroxylation reaction in eight steps.

High Accumulation and Recycling of the New Antimalarial Albitiazolium Lead to Rapid Parasite Death.

Albitiazolium is the lead compound of bisthiazolium choline analogues and exerts powerful and antimalarial activities. Here we provide new insight into the fate of albitiazolium in mice and how it exerts its pharmacological activity. We show that the drug exhibits rapid and potent activity and has very favorable pharmacokinetic and pharmacodynamic properties.

Enantiomerically pure amino-alcohol quinolines: in vitro anti-malarial activity in combination with dihydroartemisinin, cytotoxicity and in vivo efficacy in a Plasmodium berghei mouse model.

Background: As resistance to marketed anti-malarial drugs continues to spread, the need for new molecules active on Plasmodium falciparum-resistant strains grows. Pure (S) enantiomers of amino-alcohol quinolines previously displayed a good in vitro anti-malarial activity. Therefore, a more thorough assessment of their potential clinical use through a rodent model and an in vitro evaluation of their combination with artemisinin was undertaken.

In vitro antiplasmodial activity of cepharanthine.

Background: New classes of anti-malarial drugs are needed to control the alarming Plasmodium falciparum resistance toward current anti-malarial therapy. The ethnopharmacological approach allows the discovery of original chemical structures from the vegetable biodiversity. Previous studies led to the selection of a bisbenzylisoquinoline, called cepharanthine and isolated from a Cambodian plant: Stephania rotunda.

Ethnobotany, phytochemistry and pharmacology of Stephania rotunda Lour.

Ethnopharmacological Relevance: Stephania rotunda Lour. (Menispermaceae) is an important traditional medicinal plant that is grown in Southeast Asia. The stems, leaves, and tubers have been used in the Cambodian, Lao, Indian and Vietnamese folk medicine systems for years to treat a wide range of ailments, including asthma, headache, fever, and diarrhoea.

Biologically active carbazole derivatives: focus on oxazinocarbazoles and related compounds.

Four series of carbazole derivatives, including N-substituted-hydroxycarbazoles, oxazinocarbazoles, isoxazolocarbazolequinones, and pyridocarbazolequinones, were studied using diverse biological test methods such as a CE-based assay for CK2 activity measurement, a cytotoxicity assay with IPC-81 cell line, determination of MIC of carbazole derivatives as antibacterial agents, a Plasmodium falciparum susceptibility assay, and an ABCG2-mediated mitoxantrone assay. Two oxazinocarbazoles Ib and Ig showed CK2 inhibition with IC50 = 8.7 and 14.

Quantitative analysis of cepharanthine in plasma based on semiautomatic microextraction by packed sorbent combined with liquid chromatography.

The spread of Plasmodium falciparum resistance toward most of the used drugs requires new antimalarial compounds. Taking advantage of the biodiversity, the ethnopharmacological approach opens the way for the discovery and the characterization of potent original molecules. Previous works led to the selection of a bisbenzylisoquinoline, cepharanthine, extracted from Stephania rotunda, which is mainly present in Cambodia.

In vitro and in vivo combination of cepharanthine with anti-malarial drugs.

Background: Stephania rotunda is used by traditional health practitioners in Southeast Asia to treat a wide range of diseases and particularly symptoms related to malaria. Cepharanthine (CEP) is an alkaloid isolated from this plant with potential innovative antiplasmodial activity. The analysis of interactions between antiplasmodial drugs is necessary to develop new drugs combinations to prevent de novo emergence of resistance.

In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene.

Background: Dihydroartemisinin-piperaquine is a new ACT that is administered as single daily dose for three days and has been demonstrated to be tolerated and highly effective for the treatment of uncomplicated Plasmodium falciparum malaria. Piperaquine was used alone to replace chloroquine as the first-line treatment for uncomplicated malaria in China in response to increasing chloroquine resistance in the 1970s. However, the rapid emergence of piperaquine-resistant strains that resulted in the cessation of its use in China in the 1980s, suggests that there is cross-resistance between piperaquine and chloroquine.

Stability and antiviral activity against human cytomegalovirus of artemisinin derivatives.

Objectives: Artesunate, a derivative of dihydroartemisinin, itself a product of artemisinin, inhibits the replication of cytomegalovirus in vitro. In vivo, artesunate undergoes rapid conversion into the active metabolite dihydroartemisinin. The in vitro stability of the compounds and the antiviral activity of dihydroartemisinin are of great concern for the interpretation of in vitro testing.