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The therapeutic potential of novel isobenzofuranones against Naegleria fowleri
Ist Teil von
International journal for parasitology -- drugs and drug resistance, 2021-12, Vol.17, p.139-149
Ort / Verlag
Netherlands: Elsevier Ltd
Erscheinungsjahr
2021
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
The Free-Living Amoeba species, Naegleria fowleri is the causative agent of a lethal encephalitis known as Primary Amoebic Encephalitis (PAM). Moreover, most of the reported cases are often related to swimming and/or diving in aquatic environments. In addition, the current therapeutic options against PAM are not fully effective and hence, there is an urgent need to develop novel therapeutic agents against this disease. Previously isobenzofuranones compounds have been reported to present antiprotozoal and antifungal activity among others. However, to the best of our knowledge, these molecules have not been previously tested against N. fowleri. Therefore, the aim of this study was to evaluate the activity of 14 novel isobenzofuranones against this pathogenic amoeba. The most active and less toxic molecules, were assayed in order to check induction of Programmed Cell Death (PCD) in the treated amoebae. The obtained results showed that these molecules were able to eliminate N. fowleri trophozoites and also induced PCD. Therefore, the tested isobenzofuranones could be potential therapeutic candidates for the treatment of PAM.
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•A library of 14 new-aryl substituted isobezofuranones have been synthetized.•8 isobenzofuranones showed high activity against Naegleria fowleri.•QOET-1, QOET-3, QOET-34 induced programmed cell death in treated amoebae.