In Silico Evaluation of Molecular Binding Affinity, Physicochemical Properties, and ADMET Profile of Nicotine Derivatives Targeting Plasmodium falciparum DHFR and LDH
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La découverte de nouveaux candidats médicaments repose de plus en plus sur des approches computationnelles permettant une évaluation rapide de leur efficacité et de leur innocuité. Dans cette étude, six dérivés de la nicotine (C1-C6) ont été évalués par amarrage moléculaire sur deux cibles antipaludiques validées : la dihydrofolate réductase de Plasmodium falciparum (PfDHFR) et la lactate déshydrogénase de Plasmodium falciparum (PfLDH). Leurs caractéristiques physico-chimiques et leurs profils ADMET (absorption, distribution, métabolisme, excrétion et toxicité) ont également été étudiés à l’aide d’outils de prédiction in silico. Les résultats de l’amarrage ont démontré que tous les dérivés étudiés présentaient des affinités de liaison plus fortes que la molécule de nicotine d’origine pour les deux cibles protéiques. Les composés C1 et C2 ont présenté les affinités de liaison les plus favorables, ainsi que des profils pharmacocinétiques prometteurs. De plus, tous les composés étudiés satisfaisaient aux principaux critères de « drug-likeness », suggérant une bonne biodisponibilité orale et des propriétés physico-chimiques favorables. Globalement, ces résultats suggèrent que les dérivés de la nicotine, notamment les composés C1 et C2, constituent des molécules de tête prometteuses pour le développement de nouveaux agents antipaludiques. Toutefois, des études complémentaires in vitro et i
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