Immunomodulatory and Antileishmanial Activity of Phenylpropanoid Dimers Isolated from Nectandra leucantha

J Nat Prod. 2015 Apr 24;78(4):653-7. doi: 10.1021/np500809a. Epub 2015 Apr 2.

Abstract

Three phenylpropanoid dimers (1-3) including two new metabolites were isolated from the extract of the twigs of Nectandra leucantha using antileishmanial bioassay-guided fractionation. The in vitro antiparasitic activity of the isolated compounds against Leishmania donovani parasites and mammalian cytotoxicity and immunomodulatory effects were evaluated. Compounds 1-3 were effective against the intracellular amastigotes within macrophages, with IC50 values of 26.7, 17.8, and 101.9 μM, respectively. The mammalian cytotoxicity, given by the 50% cytotoxic concentration (CC50), was evaluated against peritoneal macrophages. Compounds 1 and 3 were not toxic up to 290 μM, whereas compound 2 demonstrated a CC50 value of 111.2 μM. Compounds 1-3 also suppressed production of disease exacerbatory cytokines IL-6 and IL-10 but had minimal effect on nitric oxide production in L. donovani-infected macrophages, indicating that antileishmanial activity of these compounds is mediated via an NO-independent mechanism. Therefore, these new natural products could represent promising scaffolds for drug design studies for leishmaniasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anisoles / chemistry
  • Anisoles / isolation & purification*
  • Anisoles / pharmacology*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / isolation & purification*
  • Antiprotozoal Agents / pharmacology*
  • Brazil
  • Immunologic Factors / chemistry
  • Immunologic Factors / isolation & purification*
  • Immunologic Factors / pharmacology*
  • Inhibitory Concentration 50
  • Interleukin-10
  • Interleukin-6
  • Lauraceae / chemistry*
  • Leishmania donovani / drug effects
  • Leishmaniasis / drug therapy*
  • Macrophages, Peritoneal / drug effects
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Structure
  • Nitric Oxide / metabolism
  • Phenylpropionates / chemistry
  • Phenylpropionates / isolation & purification*
  • Phenylpropionates / pharmacology*
  • Plant Stems / chemistry

Substances

  • 1-(7R-hydroxy-8-propenyl)-3-(3'-methoxy-1'-(8'-propenyl)phenoxy)-4-hydroxy-5-methoxybenzene
  • Anisoles
  • Antiprotozoal Agents
  • Immunologic Factors
  • Interleukin-6
  • Phenylpropionates
  • dehydrodieugenol B
  • Interleukin-10
  • Nitric Oxide