Antileishmanial activity and cytotoxicity of ent-beyerene diterpenoids

Bioorg Med Chem. 2019 Jan 1;27(1):153-160. doi: 10.1016/j.bmc.2018.11.030. Epub 2018 Nov 22.

Abstract

We describe the in vitro activity of two natural isomeric ent-beyerene diterpenes, several derivatives and synthetic intermediates. Beyerenols 1 and 2 showed EC50 of 4.6 ± 9.4 and 5.3 ± 9.4 μg/mL against amastigotes of L. (V) brazilensis, with SI of 5.1 and 7.7, respectively. Beyerenol 1 was synthesized from stevioside. In vivo experiments with bereyenols showed cure in 50% of hamsters infected with L. (V) brazilensis topically applied as Cream I (beyerenol 1, 0.81%, w/w) and Cream III (beyerenol 2, 1.96%, w/w). These results suggest that beyerenols are potential candidates for cutaneous leishmaniasis chemotherapy by topical application. In vitro assays of amastigotes of L. (V) brazilensis showed EC50 of 1.1 ± 0.1 and 1.3 ± 0.04 μg/mL, with SI of 3.1 and 3.5 for hydrazone intermediates 10 and 11, respectively.

Keywords: Antileishmanial; Leishmania brazilensis; Semisynthesis; Steviol; ent-Beyerene diterpenoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Diterpenes / chemical synthesis
  • Diterpenes / pharmacology
  • Diterpenes / therapeutic use*
  • Diterpenes / toxicity
  • Female
  • Humans
  • Leishmania braziliensis / drug effects
  • Leishmaniasis, Cutaneous / drug therapy*
  • Macrophages / drug effects
  • Male
  • Mesocricetus
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / pharmacology
  • Trypanocidal Agents / therapeutic use*
  • Trypanocidal Agents / toxicity

Substances

  • Diterpenes
  • Trypanocidal Agents