2. Academic Validation
  3. Antileishmanial activity of new hybrid tetrahydroquinoline and quinoline derivatives with phosphorus substituents

Antileishmanial activity of new hybrid tetrahydroquinoline and quinoline derivatives with phosphorus substituents

  • Eur J Med Chem. 2019 Jan 15:162:18-31. doi: 10.1016/j.ejmech.2018.10.065.
Ana Tejería 1,  Yolanda Pérez-Pertejo 1,  Rosa M Reguera 1,  Rubén Carbajo-Andrés 1,  Rafael Balaña-Fouce 1,  Concepción Alonso 2,  Endika Martin-Encinas 2,  Asier Selas 2,  Gloria Rubiales 2,  Francisco Palacios 3
Affiliations

Affiliations

  • 1 Departamento de Ciencias Biomédicas, Universidad de León, Campus de Vegazana s/n, 24071, León, Spain.
  • 2 Departamento de Química Orgánica I, Facultad de Farmacia and Centro de Investigación Lascaray (Lascaray Research Center), Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain.
  • 3 Departamento de Química Orgánica I, Facultad de Farmacia and Centro de Investigación Lascaray (Lascaray Research Center), Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain. Electronic address: [email protected].
PMID: 30408746 DOI: 10.1016/j.ejmech.2018.10.065
Abstract

Heterocyclic compounds, such as hybrid tetrahydroquinoline and quinoline derivatives with phosphorated groups, have been prepared by multicomponent cycloaddition reaction between phosphorus-substituted anilines, aldehydes and styrenes. The antileishmanial activity of these compounds has been evaluated on both promastigotes and intramacrophagic amastigotes of Leishmania infantum. Good antileishmanial activity of functionalized tetrahydroquinolines 4a, 5a, 6b and quinoline 8b has been observed with similar activity than the standard drug amphotericin B and close selective index (SI between 43 and 57) towards L. infantum amastigotes to amphotericin B. Special interest shows tetrahydroquinolylphosphine sulfide 5a with an EC50 value (0.61 ± 0.18 μM) similar to the standard drug amphotericin B (0.32 ± 0.05 μM) and selective index (SI = 56.87). In addition, compound 4c shows remarkable inhibition on Leishmania Topoisomerase IB. Parallel theoretical study of stereoelectronic properties, application of docking-based virtual screening methods, along with molecular electrostatic potential and predictive druggability analyses are also reported.

Keywords

DNA-Topoisomerase; Leishmania; Phosphorus substituted quinoline derivatives.

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