2. Academic Validation
  3. Evaluation of synthetic substituted 1,2-dioxanes as novel agents against human leishmaniasis

Evaluation of synthetic substituted 1,2-dioxanes as novel agents against human leishmaniasis

  • Eur J Med Chem. 2019 May 15:170:126-140. doi: 10.1016/j.ejmech.2019.02.070.
M Ortalli 1,  S Varani 2,  C Rosso 3,  A Quintavalla 4,  M Lombardo 3,  C Trombini 3
Affiliations

Affiliations

  • 1 Alma Mater Studiorum - University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine, Via Massarenti 9, 40138, Bologna, Italy.
  • 2 Alma Mater Studiorum - University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine, Via Massarenti 9, 40138, Bologna, Italy; Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138, Bologna, Italy.
  • 3 Alma Mater Studiorum - University of Bologna, Department of Chemistry "G. Ciamician", Via Selmi 2, 40126, Bologna, Italy.
  • 4 Alma Mater Studiorum - University of Bologna, Department of Chemistry "G. Ciamician", Via Selmi 2, 40126, Bologna, Italy. Electronic address: [email protected].
PMID: 30878827 DOI: 10.1016/j.ejmech.2019.02.070
Abstract

The treatment of human leishmaniasis is currently based on few compounds that are highly toxic, expensive and have a high rate of treatment failure. A number of recent studies on new drugs focuses on natural or semi-synthetic compounds. Among them, the endoperoxide artemisinin, extracted from Artemisia annua, and some of its derivatives have shown leishmanicidal activity. In the present work, a series of structurally simple, fully synthetic 1,2-dioxanes were evaluated for in vitro antileishmanial activity against promastigotes of Leishmania donovani; the cytotoxicity for mammalian cells was also assessed. The six most promising compounds in terms of activity and selectivity were further investigated for their antileishmanial activity on the promastigote forms of L. tropica, L. major and L. infantum and against L. donovani amastigotes. The good performance in terms of potency and selectivity makes these six hits promising candidates for a preliminary lead optimization as antileishmanial agents.

Keywords

Drug design; Leishmaniasis; Neglected tropical disease; Synthetic endoperoxides.

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