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

• Published in: European journal of medicinal chemistry Vol. 44; no. 4; pp. 1726 - 1730
• Main Authors: Barbosa, Ticiano P., Junior, Cláudio G.L., Silva, Fábio P.L., Lopes, Horacimone M., Figueiredo, Lucas R.F., Sousa, Suervy C.O., Batista, Guilherme N., da Silva, Thiago G., Silva, Tania M.S., de Oliveira, Márcia R., Vasconcellos, Mário L.A.A.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 01-04-2009; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Artemia - drug effects; Artemia salina Leach; Baylis–Hillman adducts; Biological and medical sciences; Green chemistry; Inhibitory Concentration 50; Leishmania - drug effects; Leishmania chagasi; Medical sciences; Organic Chemicals - chemical synthesis; Organic Chemicals - chemistry; Organic Chemicals - pharmacology; Organic Chemicals - toxicity; Pharmacology. Drug treatments; Baylis–Hillman adducts; Leishmania chagasi; Green chemistry; Artemia salina Leach; Kinetoplastida; Protozoa; Nitro compound; Baylis-Hillman adducts; Artemia salina; Toxicity; Wasteless technology; In vitro; Pyridine derivatives; Hydroxynitrile; Crustacea; Antiprotozoal agent; Arthropoda; Vinylic compound; Parasiticide; Aromatic compound; Invertebrata; Baylis-Hillman reaction; Chemical synthesis; Branchiopoda; Molecular adduct
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2008.03.016

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
°C in only 10–40
min 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
μg/mL on
A. salina; IC
50
=
25.2
μM 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
μg/mL on
A. salina Leach.; IC
50
=
4.8
μg/mL on
L. chagasi) was also a very active substance evaluated in this work on promastigote
L. chagasi.
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