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2-Phenoxy-1,4-naphthoquinones : from a multitarget antitrypanosomal to a potential antitumor profile

Prati, Federica and Bergamini, Christian and Molina, Maria Teresa and Falchi, Federico and Cavalli, Andrea and Kaiser, Marcel and Brun, Reto and Fato, Romana and Bolognesi, Maria Laura. (2015) 2-Phenoxy-1,4-naphthoquinones : from a multitarget antitrypanosomal to a potential antitumor profile. Journal of medicinal chemistry, 58 (16). pp. 6422-6434.

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Official URL: http://edoc.unibas.ch/42083/

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Abstract

A small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives was initially developed to optimize the antitrypanosomatid profile of the multitarget hit compound B6 (1). The whole series was evaluated against the three most important human trypanosomatid pathogens (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani), and two compounds (14 and 21) showed good activity, despite a concomitant mammalian cytotoxicity. Furthermore, a subset also inhibited the glycolytic TbGAPDH enzyme in vitro. In light of these results and aware of the antitumor properties of quinones, the anticancer potential of some selected derivatives was investigated. Intriguingly, the tested compounds displayed antitumor activity, while being less toxic against noncancerous cells. The observed cytotoxic potency was ascribed to a multitarget mechanism of action accounting for hGAPDH inhibition and mitochondrial toxicity. Overall, the development of further derivatives, able to finely modulate multiple pathways of cancer or parasite cell metabolism, might lead to more effective treatments against these devastating diseases.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Kaiser, Marcel and Brun, Reto
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
ISSN:0022-2623
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Dec 2017 10:49
Deposited On:21 Apr 2016 11:52

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