Improved synthesis of seven aromatic Baylis-Hillman adducts (BHA): evaluation against Artemia salina Leach. and Leishmania chagasi

Eur J Med Chem. 2009 Apr;44(4):1726-30. doi: 10.1016/j.ejmech.2008.03.016. Epub 2008 Mar 29.

Abstract

We described a very efficient procedure to prepare seven aromatic compounds (1-7), a new class of antileishmanial substances, through Baylis-Hillman reaction (BHR). With one, all the Baylis-Hillman adducts were prepared in quantitative yields by reaction of the corresponding aromatic aldehydes in acrylonitrile at 0 degrees C in only 10-40min reaction time. We present our results about the toxicities of these compounds evaluated on the microcrustaceous Artemia salina Leach. and against promastigote Leishmania chagasi. All substances evaluated in this work have showed high bioactivity. The 3-hydroxy-2-methylene-3-(4-bromopheny)propanenitrile (4) (LC(50)=30.9 microg/mL on A. salina; IC(50)=25.2 microM on L. chagasi) was the most active compound evaluated on A. salina Leach. and on promastigote L. chagasi. The 2-[hydroxy(pyridin-4-yl)methyl]acrylonitrile (7) (LC(50)=30.9 microg/mL on A. salina Leach.; IC(50)=4.8 microg/mL on L. chagasi) was also a very active substance evaluated in this work on promastigote L. chagasi.

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Antiprotozoal Agents / toxicity
  • Artemia / drug effects*
  • Inhibitory Concentration 50
  • Leishmania / drug effects*
  • Organic Chemicals / chemical synthesis*
  • Organic Chemicals / chemistry
  • Organic Chemicals / pharmacology*
  • Organic Chemicals / toxicity

Substances

  • Antiprotozoal Agents
  • Organic Chemicals