2. Academic Validation
  3. Design, synthesis and evaluation of amino-substituted 1H-phenalen-1-ones as anti-leishmanial agents

Design, synthesis and evaluation of amino-substituted 1H-phenalen-1-ones as anti-leishmanial agents

  • Eur J Med Chem. 2018 Jan 1:143:1312-1324. doi: 10.1016/j.ejmech.2017.10.032.
Mónica Blanco Freijo 1,  Atteneri López-Arencibia 2,  José E Piñero 3,  Grant McNaughton-Smith 4,  Teresa Abad-Grillo 5
Affiliations

Affiliations

  • 1 Instituto Universitario de Bio-Orgánica 'Antonio González', Departamento de Química Orgánica, Universidad de La Laguna, Avda. Fco. Sánchez 2, 38206 La Laguna, Tenerife, Spain.
  • 2 Instituto Universitario de Enfermedades Tropicales y Salud Pública de Las Islas Canarias, Laboratorio de Quimioterapias de Protozoos, Universidad de La Laguna, Tenerife, Spain.
  • 3 Instituto Universitario de Enfermedades Tropicales y Salud Pública de Las Islas Canarias, Laboratorio de Quimioterapias de Protozoos, Universidad de La Laguna, Tenerife, Spain. Electronic address: [email protected].
  • 4 Centro Atlántico del Medicamento S.A (CEAMED S.A.), PCTT, La Laguna, Tenerife, Spain.
  • 5 Instituto Universitario de Bio-Orgánica 'Antonio González', Departamento de Química Orgánica, Universidad de La Laguna, Avda. Fco. Sánchez 2, 38206 La Laguna, Tenerife, Spain. Electronic address: [email protected].
PMID: 29126735 DOI: 10.1016/j.ejmech.2017.10.032
Abstract

Screening of a designed collection of mono-substituted amino-1H-phenalen-1-ones against promastigote forms of L. donovani and L. amazonensis, identified seven compounds with anti-leishmanial activities comparable or better than the commonly prescribed anti-leishmanial drug, miltefosine. Structure-activity analysis revealed that appendages containing a basic tertiary nitrogen were favored, and that the position of the appendage also affected their potency. Like miltefosine, several of these active compounds significantly reduced the mitochondrial membrane potential in promastigotes. Further studies in amastigotes of L. amazonensis revealed that compounds 14, 15 and 33 were more active and more selective than miltefosine, with sub-micromolar potencies and selectivity indices >100.

Keywords

Amino-substituted 1H-phenalen-1-ones; Anti-leishmanial activity; Mitochondrial membrane potential; Structure-activity relationship.

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