Médicaments et molécules innovantes en développement pour la prise en charge de la tuberculose

In 2019, tuberculosis is a major public health concern around the world. This is the leading cause of death from infectious disease. In addition, the emergence of resistant strains makes the emergence of the situation even more extreme. It is important to deal with this problem and treat it quickly to avoid a possible global pandemic. Academic and industrial researches have been treated on the subject and have been developed all over the world. New solutions are proposed, either new strategies or the improvement of current strategies. This document is a bibliographic watch that groups together molecules currently in development until clinical trials. This makes it possible to establish a state of the art in this field and to bring a global vision of the fight against tuberculosis in 2019.En 2019 la tuberculose est un souci de santé public majeur, et ce à travers le monde. Il s’agit de la première cause de mortalité par maladie infectieuse. De plus, l’émergence de souches résistantes rend l’urgence de la situation encore plus extrême. Il est important d’innover face à ce problème, de traiter cela rapidement pour éviter une possible pandémie mondiale. La recherche académique et industrielle travaille actuellement activement sur ce sujet et de nombreuses molécules sont en développement partout dans le monde. Des solutions sont apportées soit grâce à de nouvelles stratégies, soit par l’amélioration des stratégies actuelles. Ce document constitue une veille bibliographique qui regroupe les médicaments existants et les molécules en développement des essais cliniques jusqu’au hit-to-lead. Cela permet d’établir un état de l’art dans ce domaine et d’apporter une vision globale de la lutte contre la tuberculose en 2019

Rapid and Efficient Access to Novel Bio-Inspired 3-Dimensional Tricyclic SpiroLactams as Privileged Structures via Meyers’ Lactamization

International audienceThe concept of privileged structure has been used as a fruitful approach for the discovery of novel biologically active molecules. A privileged structure is defined as a semi-rigid scaffold able to display substituents in multiple spatial directions and capable of providing potent and selective ligands for different biological targets through the modification of those substituents. On average, these backbones tend to exhibit improved drug-like properties and therefore represent attractive starting points for hit-to-lead optimization programs. This article promotes the rapid, reliable, and efficient synthesis of novel, highly 3-dimensional, and easily functionalized bio-inspired tricyclic spirolactams, as well as an analysis of their drug-like properties

On the Hunt for Next-Generation Antimicrobial Agents: An Online Symposium Organized Jointly by the French Society for Medicinal Chemistry (Société de Chimie Thérapeutique) and the French Microbiology Society (Société Française de Microbiologie) on 9–10 December 2021

The restrictions posed by the COVID-19 pandemic obliged the French Society for Medicinal Chemistry (Société de chimie thérapeutique) and the French Microbiology Society (Société Française de Microbiologie) to organize their joint autumn symposium (entitled “On the hunt for next-generation antimicrobial agents”) online on 9–10 December 2021. The meeting attracted more than 200 researchers from France and abroad with interests in drug discovery, antimicrobial resistance, medicinal chemistry, and related disciplines. This review summarizes the 13 invited keynote lectures. The symposium generated high-level scientific dialogue on the most recent advances in combating antimicrobial resistance. The University of Lille, the Institut Pasteur de Lille, the journal Pharmaceuticals, Oxeltis, and INCATE, sponsored the event

Tricyclic SpiroLactams Kill Mycobacteria In Vitro and In Vivo by Inhibiting Type II NADH Dehydrogenases

International audienceIt is critical that novel classes of antituberculosis drugs are developed to combat the increasing burden of infections by multidrug-resistant strains. To identify such a novel class of antibiotics, a chemical library of unique 3-D bioinspired molecules was explored revealing a promising, mycobacterium specific Tricyclic SpiroLactam (TriSLa) hit. Chemical optimization of the TriSLa scaffold delivered potent analogues with nanomolar activity against replicating and nonreplicating Mycobacterium tuberculosis. Characterization of isolated TriSLa-resistant mutants, and biochemical studies, found TriSLas to act as allosteric inhibitors of type II NADH dehydrogenases (Ndh-2 of the electron transport chain), resulting in an increase in bacterial NADH/NAD+ ratios and decreased ATP levels. TriSLas are chemically distinct from other inhibitors of Ndh-2 but share a dependence for fatty acids for activity. Finally, in vivo proof-of-concept studies showed TriSLas to protect zebrafish larvae from Mycobacterium marinum infection, suggesting a vulnerability of Ndh-2 inhibition in mycobacterial infections