ascochlorin and Trypanosomiasis--African

ascochlorin has been researched along with Trypanosomiasis--African* in 1 studies

Other Studies

1 other study(ies) available for ascochlorin and Trypanosomiasis--African

Article	Year
Pharmacophore identification of ascofuranone, potent inhibitor of cyanide-insensitive alternative oxidase of Trypanosoma brucei. Journal of biochemistry, 2013, Volume: 153, Issue:3 Trypanosoma brucei is a parasite that causes human African trypanosomiasis (HAT). The parasites depend on the cyanide-insensitive trypanosome alternative oxidase (TAO) for their vital aerobic respiration. Ascofuranone (AF), a potent and specific sub-nanomolar inhibitor of the TAO quinol oxidase, is a potential novel drug with selectivity for HAT, because mammalian hosts lack the enzyme. To elucidate not only the inhibition mechanism but also the inhibitor-enzyme interaction, AF derivatives were designed and synthesized, and the structure-activity relationship was evaluated. Here we identified the pharmacophore of AF that interacts with TAO. The detailed inhibitory profiles indicated that the 1-formyl and 6-hydroxyl groups, which might contribute to intramolecular hydrogen bonding and/or serve as hydrogen-bonding donors, were responsible for direct interaction with the enzyme. Topics: Alkenes; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Molecular Structure; Oxidoreductases; Phenols; Protozoan Proteins; Recombinant Proteins; Sesquiterpenes; Structure-Activity Relationship; Trypanosoma brucei brucei; Trypanosomiasis, African	2013

Article

Year

Pharmacophore identification of ascofuranone, potent inhibitor of cyanide-insensitive alternative oxidase of Trypanosoma brucei.

Journal of biochemistry, 2013, Volume: 153, Issue:3

Trypanosoma brucei is a parasite that causes human African trypanosomiasis (HAT). The parasites depend on the cyanide-insensitive trypanosome alternative oxidase (TAO) for their vital aerobic respiration. Ascofuranone (AF), a potent and specific sub-nanomolar inhibitor of the TAO quinol oxidase, is a potential novel drug with selectivity for HAT, because mammalian hosts lack the enzyme. To elucidate not only the inhibition mechanism but also the inhibitor-enzyme interaction, AF derivatives were designed and synthesized, and the structure-activity relationship was evaluated. Here we identified the pharmacophore of AF that interacts with TAO. The detailed inhibitory profiles indicated that the 1-formyl and 6-hydroxyl groups, which might contribute to intramolecular hydrogen bonding and/or serve as hydrogen-bonding donors, were responsible for direct interaction with the enzyme.

Topics: Alkenes; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Molecular Structure; Oxidoreductases; Phenols; Protozoan Proteins; Recombinant Proteins; Sesquiterpenes; Structure-Activity Relationship; Trypanosoma brucei brucei; Trypanosomiasis, African

2013