Improved synthesis of seven aromatic Baylis-Hillman adducts (BHA): evaluation against Artemia salina Leach. and Leishmania chagasi.
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.
Barbosa
Ticiano P
TP
Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil.
Junior
Cláudio G L
CG
Silva
Fábio P L
FP
Lopes
Horacimone M
HM
Figueiredo
Lucas R F
LR
Sousa
Suervy C O
SC
Batista
Guilherme N
GN
da Silva
Thiago G
TG
Silva
Tania M S
TM
de Oliveira
Márcia R
MR
Vasconcellos
Mário L A A
ML
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001156:Artemia / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D009930:Organic Chemicals / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000981:Antiprotozoal Agents; D009930:Organic Chemicals