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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/10756

Title: Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal-antiplasmodial activity
Authors: Sola, Irene
Castellàa, Sílvia
Viayna, Elisabet
Galdeano, Carles
Taylor, Martin C.
Gbedema, Stephen Y.
Pérez, Belén
Clos, M. Victòria
Jones, Deuan C.
Fairlamb, Alan H.
Wright, Colin W.
Kelly, John
Muñoz-Torrero, Diego
Keywords: Molecular hybridization
Trypanocidal agents
Antimalarial agents
Trypanothione reductase inhibitors
Inhibitors of -haematin formation
Brain permeability
Issue Date: 2015
Publisher: Bioorganic & Medicinal Chemistry
Citation: Sola, I., Castellà, S., Viayna, E., Galdeano, C., Taylor, M.C., Gbedema, S.Y., Pérez, B., Victòria Clos, M., Jones, D.C., Fairlamb, A.H., Wright, C.W., Kelly, J.M., Muñoz-Torrero, D., Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidalantiplasmodial activity, Bioorganic & Medicinal Chemistry (2015), doi: http://dx.doi.org/10.1016/j.bmc. 2015.01.031
Abstract: Dual submicromolar trypanocidal-antiplasmodial compounds have been identified by screening and chemical synthesis of 4-aminoquinoline-based heterodimeric compounds of three different structural classes. In Trypanosoma brucei, inhibition of the enzyme trypanothione reductase seems to be involved in the potent trypanocidal activity of these heterodimers, although it is probably not the main biological target. Regarding antiplasmodial activity, the heterodimers seem to share the mode of action of the antimalarial drug chloroquine, which involves inhibition of the haem detoxification process. Interestingly, all of these heterodimers display good brain permeabilities, thereby being potentially useful for late stage human African trypanosomiasis. Future optimization of these compounds should focus mainly on decreasing cytotoxicity and acetylcholinesterase inhibitory activity.
Description: An article published by Sola, I., Castellà, S., Viayna, E., Galdeano, C., Taylor, M.C., Gbedema, S.Y., Pérez, B., Victòria Clos, M., Jones, D.C., Fairlamb, A.H., Wright, C.W., Kelly, J.M., Muñoz-Torrero, D., Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidalantiplasmodial activity, Bioorganic & Medicinal Chemistry (2015), doi: http://dx.doi.org/10.1016/j.bmc. 2015.01.031
URI: http://hdl.handle.net/123456789/10756
Appears in Collections:College of Health Sciences

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