Autofluorescent antimalarials by hybridization of artemisinin and coumarin: in vitro / in vivo studies and live-cell imaging.

Autor: Herrmann L; Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander-Universität Erlangen-Nürnberg Nikolaus-Fiebiger-Straße 10 91054 Erlangen Germany svetlana.tsogoeva@fau.de., Leidenberger M; Institute of Medical Biotechnology, Friedrich-Alexander-Universität Erlangen-Nürnberg Paul-Gordon-Straße 3 91052 Erlangen Germany barbara.kappes@fau.de., Sacramento de Morais A; Instituto Gonçalo Moniz Fundação Oswaldo Cruz Salvador 40296-710 Brazil diogo.magalhaes@fiocruz.br., Mai C; Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander-Universität Erlangen-Nürnberg Nikolaus-Fiebiger-Straße 10 91054 Erlangen Germany svetlana.tsogoeva@fau.de., Çapci A; Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander-Universität Erlangen-Nürnberg Nikolaus-Fiebiger-Straße 10 91054 Erlangen Germany svetlana.tsogoeva@fau.de., da Cruz Borges Silva M; Instituto Gonçalo Moniz Fundação Oswaldo Cruz Salvador 40296-710 Brazil diogo.magalhaes@fiocruz.br., Plass F; Leibniz Institute of Surface Engineering (IOM) Permoserstrasse 15 04318 Leipzig Germany.; Physical Chemistry Chair I, Friedrich-Alexander-Universität Erlangen-Nürnberg Egerlandstrasse 3 91058 Erlangen Germany., Kahnt A; Leibniz Institute of Surface Engineering (IOM) Permoserstrasse 15 04318 Leipzig Germany.; Physical Chemistry Chair I, Friedrich-Alexander-Universität Erlangen-Nürnberg Egerlandstrasse 3 91058 Erlangen Germany., Moreira DRM; Instituto Gonçalo Moniz Fundação Oswaldo Cruz Salvador 40296-710 Brazil diogo.magalhaes@fiocruz.br., Kappes B; Institute of Medical Biotechnology, Friedrich-Alexander-Universität Erlangen-Nürnberg Paul-Gordon-Straße 3 91052 Erlangen Germany barbara.kappes@fau.de., Tsogoeva SB; Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander-Universität Erlangen-Nürnberg Nikolaus-Fiebiger-Straße 10 91054 Erlangen Germany svetlana.tsogoeva@fau.de.
Jazyk: angličtina
Zdroj: Chemical science [Chem Sci] 2023 Oct 24; Vol. 14 (45), pp. 12941-12952. Date of Electronic Publication: 2023 Oct 24 (Print Publication: 2023).
DOI: 10.1039/d3sc03661h
Abstrakt: Malaria is one of our planet's most widespread and deadliest diseases, and there is an ever-consistent need for new and improved pharmaceuticals. Natural products have been an essential source of hit and lead compounds for drug discovery. Antimalarial drug artemisinin (ART), a highly effective natural product, is an enantiopure sesquiterpene lactone and occurs in Artemisia annua L. The development of improved antimalarial drugs, which are highly potent and at the same time inherently fluorescent is particularly favorable and highly desirable since they can be used for live-cell imaging, avoiding the requirement of the drug's linkage to an external fluorescent label. Herein, we present the first antimalarial autofluorescent artemisinin-coumarin hybrids with high fluorescence quantum yields of up to 0.94 and exhibiting excellent activity in vitro against CQ-resistant and multidrug-resistant P. falciparum strains (IC 50 (Dd2) down to 0.5 nM; IC 50 (K1) down to 0.3 nM) compared to reference drugs CQ (IC 50 (Dd2) 165.3 nM; IC 50 (K1) 302.8 nM) and artemisinin (IC 50 (Dd2) 11.3 nM; IC 50 (K1) 5.4 nM). Furthermore, a clear correlation between in vitro potency and in vivo efficacy of antimalarial autofluorescent hybrids was demonstrated. Moreover, deliberately designed autofluorescent artemisinin-coumarin hybrids, were not only able to overcome drug resistance, they were also of high value in investigating their mode of action via time-dependent imaging resolution in living P. falciparum -infected red blood cells.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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