drug discovery
Mechanisms of Action: Physiological EffectsArgentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by ChemoproteomicsParacoccidioidomycosis (PCM) is the cause of many deaths from systemic mycoses. The etiological agents of PCM belong to the Paracoccidioides genus, which is restricted to Latin America.
Experimental TherapeuticsCyclic Nucleotide-Specific Phosphodiesterases as Potential Drug Targets for Anti-Leishmania TherapyThe available treatments for leishmaniasis are less than optimal due to inadequate efficacy, toxic side effects, and the emergence of resistant strains, clearly endorsing the urgent need for discovery and development of novel drug candidates. Ideally, these should act via an alternative mechanism of action to avoid cross-resistance with the current drugs.
- PharmacologyUCT943, a Next-Generation Plasmodium falciparum PI4K Inhibitor Preclinical Candidate for the Treatment of Malaria
The 2-aminopyridine MMV048 was the first drug candidate inhibiting Plasmodium phosphatidylinositol 4-kinase (PI4K), a novel drug target for malaria, to enter clinical development. In an effort to identify the next generation of PI4K inhibitors, the series was optimized to improve properties such as solubility and antiplasmodial potency across the parasite life cycle,...
- Mechanisms of Action: Physiological EffectsAntitrypanosomal 8-Hydroxy-Naphthyridines Are Chelators of Divalent Transition Metals
The lack of information regarding the mechanisms of action (MoA) or specific molecular targets of phenotypically active compounds can prove a barrier to their development as chemotherapeutic agents. Here, we report the results of our orthogonal genetic, molecular, and biochemical studies to determine the MoA of a novel 7-substituted 8-hydroxy-1,6-naphthyridine (8-HNT) series that displays promising activity against...
- Experimental TherapeuticsHC2091 Kills Mycobacterium tuberculosis by Targeting the MmpL3 Mycolic Acid Transporter
- Mechanisms of ResistanceImidazopyridine Compounds Inhibit Mycobacterial Growth by Depleting ATP Levels
- Experimental TherapeuticsSelective Killing of Dormant Mycobacterium tuberculosis by Marine Natural Products