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

被引：34

作者：

Barbosa, Ticiano P. ^{[1
]}

Junior, Claudio G. L. ^{[1
]}

Silva, Fabio P. L. ^{[1
]}

Lopes, Horacimone M. ^{[1
]}

Figueiredo, Lucas R. F. ^{[1
]}

Sousa, Suervy C. O. ^{[1
]}

Batista, Guilherme N. ^{[2
]}

da Silva, Thiago G. ^{[3
]}

Silva, Tania M. S. ^{[3
,4
]}

de Oliveira, Marcia R. ^{[2
,3
]}

Vasconcellos, Mario L. A. A. ^{[1
]}

机构：

[1] Univ Fed Paraiba, Dept Quim, BR-58059900 Joao Pessoa, Paraiba, Brazil

[2] Univ Fed Paraiba, Dept Biol Mol, BR-58059900 Joao Pessoa, Paraiba, Brazil

[3] Univ Fed Paraiba, Lab Tecnol Farmaceut, BR-58059900 Joao Pessoa, Paraiba, Brazil

[4] Univ Fed Bahia, Inst Multidisciplinar Saude, BR-45055090 Vitoria Da Conquista, BA, Brazil

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 04期

关键词：

Baylis-Hillman adducts; Green chemistry; Leishmania chagasi; Artemia salina Leach; (+/-)-CIS-(6-ETHYL-TETRAHYDROPYRAN-2-YL)-FORMIC ACID; MOLLUSCICIDAL ACTIVITY; ANTIMALARIAL ACTIVITY; MECHANISM; CATALYST; HEXAMETHYLENETETRAMINE; ALDEHYDES; ACRYLATE;

D O I：

10.1016/j.ejmech.2008.03.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 10-40 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) (LC50 = 30.9 mu g/mL on A. salina; IC50 = 25.2 mu M 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) (LC50 = 30.9 mu g/mL on A. salina Leach.; IC50 = 4.8 mu g/mL on L. chagasi) was also a very active substance evaluated in this work on promastigote L. chagasi. (c) 2008 Elsevier Masson SAS. All rights reserved.

引用

页码：1726 / 1730

页数：5

共 31 条

[1] Reevaluation of the mechanism of the Baylis-Hillman reaction: Implications for asymmetric catalysis [J].

Aggarwal, VK ;

Fulford, SY ;

Lloyd-Jones, GC .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2005, 44 (11) :1706-1708

[2] New 1,2,3,4-tetrahydro-1-aza-anthraquinones and 2-aminoalkyl compounds from norlapachol with molluscicidal activity [J].

Barbosa, TP ;

Camara, CA ;

Silva, TMS ;

Martins, RM ;

Pinto, AC ;

Vargas, MD .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (23) :6464-6469

[3] Recent advances in the Baylis-Hillman reaction and applications [J].

Basavaiah, D ;

Rao, AJ ;

Satyanarayana, T .

CHEMICAL REVIEWS, 2003, 103 (03) :811-891

[4]

Baylis A.B., 1972, CHEM ABSTR, V77, P34174

[5]

Caldas A J, 2001, Rev Soc Bras Med Trop, V34, P445, DOI 10.1590/S0037-86822001000500007

[6] Synthesis of substituted 1,3,5-triazines and toxicity evaluation against Artemia salina Leach. [J].

Cavalcante, MF ;

de Oliveira, MCC ;

Velandia, JR ;

Echevarria, A .

QUIMICA NOVA, 2000, 23 (01) :20-22

[7] Ultrasound in Baylis-Hillman reactions with aliphatic and aromatic aldehydes: scope and limitations [J].

Coelho, F ;

Almeida, WP ;

Veronese, D ;

Mateus, CR ;

Lopes, ECS ;

Rossi, RC ;

Silveira, GPC ;

Pavam, CH .

TETRAHEDRON, 2002, 58 (37) :7437-7447

[8] Leishmaniasis - current chemotherapy and recent advances in the search for novel drugs [J].

Croft, SL ;

Coombs, GH .

TRENDS IN PARASITOLOGY, 2003, 19 (11) :502-508

[9] Drug resistance in leishmaniasis [J].

Croft, SL ;

Sundar, S ;

Fairlamb, AH .

CLINICAL MICROBIOLOGY REVIEWS, 2006, 19 (01) :111-+

[10] High selective leishmanicidal activity of 3-hydroxy-2-methylene-3-(4-bromophenyl)propanenitrile and analogous compounds [J].

de Souza, R. O. M. A. ;

Pereira, V. L. P. ;

Muzitano, M. F. ;

Falcao, C. A. B. ;

Rossi-Bergmann, B. ;

Filho, E. B. A. ;

Vasconcellos, M. L. A. A. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2007, 42 (01) :99-102

← 1 2 3 4 →