4.4 Article

The therapeutic potential of novel isobenzofuranones against Naegleria fowleri

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.ijpddr.2021.09.004

Keywords

Naegleria; Therapeutics; Isobenzofuranones; Programmed cell death; Encephalitis

Funding

  1. Instituto de Salud Carlos III, Spain [PI18/01380]
  2. RICET, from Programa Redes Tematicas de Investigacion Cooperativa, FIS (Ministerio Espanol de Salud, Madrid, Spain) [RD16/0027/0001]
  3. FEDER
  4. Agustin de Bethancourt Programme (Cabildo de Tenerife, TFinnova Programme - MEDI)
  5. Agustin de Bethancourt Programme (Cabildo de Tenerife, TFinnova Programme - FDCAN)
  6. Agencia Canaria de Investigacion, Innovacion y Sociedad de la Informacion (ACIISI)
  7. Spanish Ministry of Science, Innovation and Universities (MICINN), State Research Agency (AEI) [PGC2018-094503-B-C21]
  8. European Regional Development Funds (ERDF) [PGC2018-094503-B-C21]

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The study evaluated the activity of 14 novel isobenzofuranones against the pathogenic amoeba Naegleria fowleri, with some compounds showing the ability to eliminate trophozoites and induce programmed cell death. These tested compounds could potentially serve as therapeutic candidates for the treatment of Primary Amoebic Encephalitis.
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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