oxadiazoles and Leishmaniasis--Visceral

oxadiazoles has been researched along with Leishmaniasis--Visceral* in 2 studies

Other Studies

2 other study(ies) available for oxadiazoles and Leishmaniasis--Visceral

Article	Year
Hierarchical Clustering and Target-Independent QSAR for Antileishmanial Oxazole and Oxadiazole Derivatives. International journal of molecular sciences, 2022, Aug-10, Volume: 23, Issue:16 Leishmaniasis is a neglected tropical disease that kills more than 20,000 people each year. The chemotherapy available for the treatment of the disease is limited, and novel approaches to discover novel drugs are urgently needed. Herein, 2D- and 4D-quantitative structure-activity relationship (QSAR) models were developed for a series of oxazole and oxadiazole derivatives that are active against Topics: Antiprotozoal Agents; Cluster Analysis; Humans; Leishmaniasis, Visceral; Oxadiazoles; Oxazoles; Quantitative Structure-Activity Relationship	2022
VFV as a New Effective CYP51 Structure-Derived Drug Candidate for Chagas Disease and Visceral Leishmaniasis. The Journal of infectious diseases, 2015, Nov-01, Volume: 212, Issue:9 Sterol 14α-demethylases (CYP51) are the enzymes essential for sterol biosynthesis. They serve as clinical targets for antifungal azoles and are considered as targets for treatment of human Trypanosomatidae infections. Recently, we have shown that VNI, a potent and selective inhibitor of trypanosomal CYP51 that we identified and structurally characterized in complex with the enzyme, can cure the acute and chronic forms of Chagas disease. The purpose of this work was to apply the CYP51 structure/function for further development of the VNI scaffold. As anticipated, VFV (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide, the derivative designed to fill the deepest portion of the CYP51 substrate-binding cavity, reveals a broader antiprotozoan spectrum of action. It has stronger antiparasitic activity in cellular experiments, cures the experimental Chagas disease with 100% efficacy, and suppresses visceral leishmaniasis by 89% (vs 60% for VNI). Oral bioavailability, low off-target activity, favorable pharmacokinetics and tissue distribution characterize VFV as a promising new drug candidate. Topics: Animals; Antiprotozoal Agents; Benzamides; Biotransformation; Chagas Disease; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Disease Models, Animal; Female; Humans; Imidazoles; Inhibitory Concentration 50; Leishmaniasis, Visceral; Mice; Mice, Inbred BALB C; Microsomes, Liver; Molecular Structure; Oxadiazoles; Rats; Structure-Activity Relationship; Tissue Distribution; Trypanosoma cruzi	2015

Article

Year

Hierarchical Clustering and Target-Independent QSAR for Antileishmanial Oxazole and Oxadiazole Derivatives.

International journal of molecular sciences, 2022, Aug-10, Volume: 23, Issue:16

Leishmaniasis is a neglected tropical disease that kills more than 20,000 people each year. The chemotherapy available for the treatment of the disease is limited, and novel approaches to discover novel drugs are urgently needed. Herein, 2D- and 4D-quantitative structure-activity relationship (QSAR) models were developed for a series of oxazole and oxadiazole derivatives that are active against

Topics: Antiprotozoal Agents; Cluster Analysis; Humans; Leishmaniasis, Visceral; Oxadiazoles; Oxazoles; Quantitative Structure-Activity Relationship

2022

VFV as a New Effective CYP51 Structure-Derived Drug Candidate for Chagas Disease and Visceral Leishmaniasis.

The Journal of infectious diseases, 2015, Nov-01, Volume: 212, Issue:9

Sterol 14α-demethylases (CYP51) are the enzymes essential for sterol biosynthesis. They serve as clinical targets for antifungal azoles and are considered as targets for treatment of human Trypanosomatidae infections. Recently, we have shown that VNI, a potent and selective inhibitor of trypanosomal CYP51 that we identified and structurally characterized in complex with the enzyme, can cure the acute and chronic forms of Chagas disease. The purpose of this work was to apply the CYP51 structure/function for further development of the VNI scaffold. As anticipated, VFV (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide, the derivative designed to fill the deepest portion of the CYP51 substrate-binding cavity, reveals a broader antiprotozoan spectrum of action. It has stronger antiparasitic activity in cellular experiments, cures the experimental Chagas disease with 100% efficacy, and suppresses visceral leishmaniasis by 89% (vs 60% for VNI). Oral bioavailability, low off-target activity, favorable pharmacokinetics and tissue distribution characterize VFV as a promising new drug candidate.

Topics: Animals; Antiprotozoal Agents; Benzamides; Biotransformation; Chagas Disease; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Disease Models, Animal; Female; Humans; Imidazoles; Inhibitory Concentration 50; Leishmaniasis, Visceral; Mice; Mice, Inbred BALB C; Microsomes, Liver; Molecular Structure; Oxadiazoles; Rats; Structure-Activity Relationship; Tissue Distribution; Trypanosoma cruzi

2015