Chemotherapy of leishmaniasis part XIII: design and synthesis of novel heteroretinoid-bisbenzylidine ketone hybrids as antileishmanial agents

Bioorg Med Chem Lett. 2015 Jan 15;25(2):410-3. doi: 10.1016/j.bmcl.2014.09.078. Epub 2014 Oct 2.

Abstract

Some novel heteroretinoid-bisbenzylidine ketone hybrids have been synthesized and evaluated for their in vitro antileishmanial activity against intramacrophagic amastigotes of Leishmania donovani. Among all the nine synthetic compounds, five compounds (7c, 7d and 7f-h) have shown significant (less than 7μM) activity against intramacrophagic amastigotes. The IC50 values of these compounds were found better than the reference drugs sodium stibogluconate (SSG) and miltefosine. This study helped us in identifying the new class of compounds that could be exploited as potent antileishmanial agents.

Keywords: Bisbenzylidine ketone; Heteroretinoid; In vitro activity; Leishmania donovani.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimony Sodium Gluconate / pharmacology
  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chlorocebus aethiops
  • Inhibitory Concentration 50
  • Ketones / chemical synthesis*
  • Leishmania donovani / drug effects*
  • Leishmaniasis / drug therapy*
  • Leishmaniasis / parasitology
  • Macrophages / drug effects
  • Macrophages / parasitology
  • Mice
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / pharmacology
  • Retinoids / chemistry*
  • Structure-Activity Relationship
  • Vero Cells

Substances

  • Antiprotozoal Agents
  • Ketones
  • Retinoids
  • Phosphorylcholine
  • miltefosine
  • Antimony Sodium Gluconate