Evaluation of In Vitro Inhibition of -Hematin Formation: A Step Towards a Comprehensive Understanding of the Mechanism of Action of New Arylamino Alcohols.

Currently, artemisinin-based combination therapy is recommended as first-line treatment of uncomplicated malaria. Arylamino alcohols (AAAs) such as mefloquine (MQ) are the preferred partner drugs due to their longer half-life, reliable absorption and strong antimalarial activity. However, the mode of action of MQ remains poorly understood and its neurotoxicity limits its use.

Synthesis of New Enantiopure Aminoalcohol Fluorenes as Promising Antimalarial Compounds.

Herein, we report the design, synthesis, and characterisation of a new library of enantiopure aminoalcohol fluorenes, as well as their in vitro evaluation for biological properties, including activity against two strains of P. falciparum (3D7 and W2) and cytotoxicity on the HepG2 cell line. All tested compounds exhibited good to excellent antimalarial potency with IC values ranging from 0.

Processes controlling geogenic arsenic distribution in soils formed from iron-rich sedimentary rocks.

Soils formed from Fe-rich sedimentary rocks can contain elevated As contents. Although the geogenic origin of As in these soils is recognized, the processes controlling its distribution within soil profiles and its mobility in topsoils are still unclear, limiting effective prediction of soils with potentially hazardous As contents for human health/ecosystems. We investigated 10 soil profiles (0-85 cm) formed from the As- and Fe-rich Aubange Formation in Belgian Lorraine.

Efficacy of mefloquine and its enantiomers in a murine model of Mycobacterium avium infection.

The treatment of Mycobacterium avium infections is still long, complex, and often poorly tolerated, besides emergence of resistances. New active molecules that are more effective and better tolerated are deeply needed. Mefloquine and its enantiomers ((+) Erythro-mefloquine ((+)-EMQ) and (-)-Erythro-mefloquine ((-)-EMQ)) have shown efficacy in both in vitro and in vivo, in a mouse model of M.

Aminopyridines in the development of drug candidates against protozoan neglected tropical diseases.

Neglected tropical diseases (NTDs) pose a major threat in tropical zones for impoverished populations. Difficulty of access, adverse effects or low efficacy limit the use of current therapeutic options. Therefore, development of new drugs against NTDs is a necessity.

Structural and biochemical characterization of SmoPG1, an exo-polygalacturonase from Selaginella moellendorffii.

Polygalacturonases (PGs) can modulate chemistry and mechanical properties of the plant cell wall through the degradation of pectins, one of its major constituents. PGs are largely used in food, beverage, textile, and paper industries to increase processes' performances. To improve the use of PGs, knowledge of their biochemical, structural and functional features is of prime importance.

The Ground State of Epitaxial Germanene on Ag(111).

Two-dimensional (2D) honeycomb lattices beyond graphene, such as germanene, appear very promising due to their outstanding electronic properties, such as the quantum spin Hall effects. While there have been many claims of germanene monolayers up to now, no experimental evidence of a honeycomb structure has been provided up to now for these grown monolayers. Using scanning tunneling microscopy (STM), surface X-ray diffraction (SXRD), and density functional theory, we have elucidated the Ge-induced reconstruction on Ag(111).

A Review of Fatty Acid Biosynthesis Enzyme Inhibitors as Promising Antimicrobial Drugs.

Resistance to antimicrobial drugs is currently a serious threat to human health. Consequently, we are facing an urgent need for new antimicrobial drugs acting with original modes of action. The ubiquitous and widely conserved microbial fatty acid biosynthesis pathway, called FAS-II system, represents a potential target to tackle antimicrobial resistance.

Design, Synthesis, and Antiprotozoal Evaluation of New Promising 2,9-[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline Derivatives, a Potential Alternative Scaffold to Drug Efflux.

A series of novel 2,9-[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives was designed, synthesized, and evaluated in vitro against three protozoan parasites (, and ). Pharmacological results showed antiprotozoal activity with IC values in the sub and μM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells.

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.

Design of a Protein with Improved Thermal Stability by an Evolution-Based Generative Model.

Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes.

The Influence of Short Motifs on the Anticancer Activity of HB43 Peptide.

Despite the remarkable similarity in amino acid composition, many anticancer peptides (ACPs) display significant differences in terms of activity. This strongly suggests that particular relative dispositions of amino acids (motifs) play a role in the interaction with their biological target, which is often the cell membrane. To better verify this hypothesis, we intentionally modify HB43, an ACP active against a wide variety of cancers.

The potential of antifungal peptide Sesquin as natural food preservative.

Sesquin is a wide spectrum antimicrobial peptide displaying a remarkable activity on fungi. Contrarily to most antimicrobial peptides, it presents an overall negative charge. In the present study, we elucidate the molecular basis of its mode of action towards biomimetic membranes by NMR and MD experiments.

The Pharmacological and Structural Basis of the AahII-Na1.5 Interaction and Modulation by the Anti-AahII Nb10 Nanobody.

Scorpion α-toxins are neurotoxins that target the fast inactivation mechanism of voltage-gated sodium (Na) channels leading to several neuro- and cardiotoxic effects in mammals. The toxin AahII is the most active α-toxin from the North African scorpion that slows the fast inactivation of Na channels. To fight scorpion envenomation, an anti-AahII nanobody named NbAahII10 (Nb10) was developed.

Quorum Sensing Inhibitors to Quench Pathogenicity.

The emergence and the dissemination of multidrug-resistant bacteria constitute a major public health issue. Among incriminated Gram-negative bacteria, has been designated by the WHO as a critical priority threat. During the infection process, this pathogen secretes various virulence factors in order to adhere and colonize host tissues.

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.

The impact of phosphatidylserine exposure on cancer cell membranes on the activity of the anticancer peptide HB43.

HB43 (FAKLLAKLAKKLL) is a synthetic peptide active against cell lines derived from breast, colon, melanoma, lung, prostate, and cervical cancers. Despite its remarkable spectrum of activity, the mechanism of action at the molecular level has never been investigated, preventing further optimization of its selectivity. The alternation of charged and hydrophobic residues suggests amphipathicity, but the formation of alpha-helical structure seems discouraged by its short length and the large number of positively charged residues.

A novel multi-target strategy to attenuate the progression of Parkinson's disease by diamine hybrid AGE/ALE inhibitor.

Instead of a conventional 'one-drug-one-target approach', this article presents a novel multi-target approach with a concept of trapping simultaneously as many detrimental factors as possible involved in the progression of Parkinson's disease. These factors include reactive carbonyl species, reactive oxygen species, FeCu and ortho-quinones (-quinone), in particular. Different from the known multi-target strategies for Parkinson's disease, it is a sort of 'vacuum cleaning' strategy.

Antimalarial Drug Discovery: From Quinine to the Most Recent Promising Clinical Drug Candidates.

Malaria is a tropical threatening disease caused by Plasmodium parasites, resulting in 409,000 deaths in 2019. The delay of mortality and morbidity has been compounded by the widespread of drug resistant parasites from Southeast Asia since two decades. The emergence of artemisinin-resistant Plasmodium in Africa, where most cases are accounted, highlights the urgent need for new medicines.

A review of current and promising nontuberculous mycobacteria antibiotics.

Nontuberculous mycobacteria infections are a growing concern, and their incidence has been increasing worldwide in recent years. Current treatments are not necessarily useful because many were initially designed to work against other bacteria, such as . In addition, inadequate treatment means that resistant strains are increasingly appearing, particularly for , one of the most virulent nontuberculous mycobacteria.

Efflux Pump Overexpression Profiling in Acinetobacter baumannii and Study of New 1-(1-Naphthylmethyl)-Piperazine Analogs as Potential Efflux Inhibitors.

Overexpression of efflux pumps extruding antibiotics currently used for the treatment of Acinetobacter baumannii infections has been described as an important mechanism causing antibiotic resistance. The first aim of this work was to phenotypically evaluate the overexpression of efflux pumps on a collection of 124 ciprofloxacin-resistant A. baumannii strains.

Antimicrobial Bombinin-like Peptide 3 Selectively Recognizes and Inserts into Bacterial Biomimetic Bilayers in Multiple Steps.

Bombinins are a wide family of antimicrobial peptides from skin. By sequence clustering, we highlighted at least three families named A, B, and H, which might exert antibacterial activity by different modes of action. In this work, we study bombinin-like peptide 3 (BLP-3) as a nonhemolytic representative of the quite unexplored class A due to its appealing activity toward WHO-priority-list bacteria such as , , and .

Antimicrobial Peptide K11 Selectively Recognizes Bacterial Biomimetic Membranes and Acts by Twisting Their Bilayers.

K11 is a synthetic peptide originating from the introduction of a lysine residue in position 11 within the sequence of a rationally designed antibacterial scaffold. Despite its remarkable antibacterial properties towards many ESKAPE bacteria and its optimal therapeutic index (320), a detailed description of its mechanism of action is missing. As most antimicrobial peptides act by destabilizing the membranes of the target organisms, we investigated the interaction of K11 with biomimetic membranes of various phospholipid compositions by liquid and solid-state NMR.