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Fasciola
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Animal fascioliasis may be treated with five categories of drugs: (1) halogenated phenols such as bithionol (Bitin), hexachlorophene (Bilevon), and nitroxynil (Trodax); (2) salicylanilides such as closantel (Flukiver and Supaverm) and rafoxanide (Flukanide and Ranizole); (3) benzimidazoles such as triclabendazole (Fasinex), albendazole (Vermitan and Valbazen), mebendazol (Telmin), and luxabendazole (Fluxacur); (4) sulfonamides such as clorsulon (Ivomec Plus); and (5) phenoxyalkanes such as diamphenetide (Coriban). Although triclabendazole resistance is noted in ruminant F. hepatica infection across Europe, South America, and Australia, no such resistance has been reported in ruminant F. gigantica infection [51].
Halogen bonding in halocarbon-protein complexes and computational tools for rational drug design
Published in Expert Opinion on Drug Discovery, 2019
Paulo J. Costa, Rafael Nunes, Diogo Vila-Viçosa
An interesting report on the use of computational tools to guide experimental work in the context of halocarbon–protein interactions was published by Weiliang Zhu and co-workers [112] featuring their own XBScoreQM scoring function (Section 4) implemented in their D3DOCKxb software. The authors aimed at the efficient repositioning of organohalogen drugs, developing potent B-Raf protein kinase mutant V600E inhibitors via docking and bioassays. Notice that drug repositioning is quite advantageous given the reduced development cost and a lower probability of failure due to safety risks. A total of 1634 organohalogen drugs were retrieved from the Comprehensive Medicinal Chemistry database (CMC) and docked against two B-Raf structures, one complexed with sorafenib, 14 (PDB ID: 1UWJ), and the other with PLX4720, 15 (PDB ID: 3C4C). From these, 67 compounds whose score was higher than the crystallized inhibitor and whose binding poses showed the existence of halogen bonds were selected. Visual inspection of the results allowed the selection of three commercial drugs for experimental assays, namely rafoxanide, closantel, and cypermethrin. The first two drugs showed potent activity against B-Raf V600E (IC50 = 0.07μM and 1.90μM, respectively) while the latter was inactive.
Efflux in Gram-negative bacteria: what are the latest opportunities for drug discovery?
Published in Expert Opinion on Drug Discovery, 2023
Teresa Gil-Gil, Pablo Laborda, Luz Edith Ochoa-Sánchez, José Luis Martínez, Sara Hernando-Amado
Gram-negative bacteria possess innate resistance to clinically approved salicylanilide compounds, such as niclosamide, oxyclozanide, closantel, and rafoxanide, which are PMF-disrupting compounds that might potentiate the activity of diverse antibiotics through the disruption of the efflux. These compounds cross the outer membrane but are expelled from the cell via PMF-dependent mediated efflux. Then, when efflux is inhibited, or the membrane is disrupted via compounds such as colistin, salicylanilides uncouple the electron transport chain, dissipate the PMF, increase oxygen consumption, and decrease ATP production [120].