In recent decades, there has been a substantial increase fungal infection (IFI), posing a significant threat to human health. Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus are the predominant pathogens responsible for the majority of IFIs in clinical settings. Despite advances in antifungal therapy, IFIs remain a major cause of morbidity and mortality, especially in immunocompromised and HIV-infected patients. The primary therapeutic families for fungal infections include polyenes, fluoropyrimidines, azoles, allylamines, and echinocandins. However, these antifungal...

This study examined the possibility of using innovative isoxazole derivatives as agents for treating liver cancer, combining several computational methods. A reliable model (QSAR) was used to identify six compounds (Pr1-Pr6) with high anticancer activity compared to that of the anticancer drug SORAFENIB (SOR). The Lipinski characteristics and synthetic accessibility coefficient of the newly developed compounds suggest their potential for therapeutic use. Candidate Pr3 has a stronger binding affinity with the target receptors (PDB ID: 1QX3 and 2AR9) compared to the other compounds. The study...

La découverte et le développement de médicaments sont une pratique coûteuse et longue, et les approches de conception de médicaments assistée par ordinateur gagnent en popularité dans l'industrie pharmaceutique pour accélérer le processus. Avec l'aide de ses approches, les scientifiques peuvent se concentrer sur les composés les plus performants afin de minimiser les difficultés des tests synthétiques et biologiques. Autour de cet axe s'articule les travaux de cette thèse, dont l'objectif principal est la proposition des nouveaux médicaments candidats à base d'isoxazole en...

Die Entdeckung und Entwicklung von Medikamenten ist eine kostspielige und zeitaufwändige Praxis, und Ansätze für das computergestützte Medikamentendesign werden in der Pharmaindustrie immer beliebter, um den Prozess zu beschleunigen. Mithilfe ihrer Ansätze können sich die Wissenschaftler auf die leistungsfähigsten Verbindungen konzentrieren, um die Schwierigkeiten synthetischer und biologischer Tests zu minimieren. Um diese Achse herum gliedert sich die Arbeit dieser Dissertation, deren Hauptziel es ist, neue Wirkstoffkandidaten auf Isoxazolbasis vorzuschlagen, indem sie sich einiger...

Drug discovery and development is an expensive and time-consuming practice, and computer-aided drug design approaches are gaining in popularity in the pharmaceutical industry to speed up the process. With the help of these approaches, scientists can focus on the most effective compounds to minimize the difficulties of synthetic and biological testing. The main objective of this thesis is to propose new isoxazole-based drug candidates using a number of in-silico approaches, including QSAR modeling, pharmacokinetic properties and toxicity evaluation, ligand-receptor complex stability...