Design, synthesis and in vitro trypanocidal and leishmanicidal activities of novel semicarbazone derivatives

被引：21

作者：

Alves, Marina A. ^{[1
,2
]}

de Queiroz, Aline C. ^{[1
,3
]}

Alexandre-Moreira, Magna Suzana ^{[1
,3
]}

Varela, Javier ^{[4
]}

Cerecetto, Hugo ^{[4
]}

Gonzalez, Mercedes ^{[4
]}

Doriguetto, Antonio C. ^{[1
,5
]}

Landre, Iara M. ^{[1
,5
]}

Barreiro, Eliezer J. ^{[1
,2
]}

Lima, Lidia M. ^{[1
,2
]}

机构：

[1] Univ Fed Rio de Janeiro, Inst Nacl Ciencia & Tecnol Farmacos & Medicamento, Lab Avaliacao & Sintese Subst Bioat, CCS, BR-21941971 Rio De Janeiro, RJ, Brazil

[2] Univ Fed Rio de Janeiro, Inst Quim, Programa Posgrad Quim, BR-21941902 Rio De Janeiro, RJ, Brazil

[3] Univ Fed Alagoas, Inst Ciencias Biol & Saude, LaFI Lab Farmacol & Imunidade, Maceio, AL, Brazil

[4] Univ Republica, Fac Ciencias, Lab Quim Organ, Grp Quim Med, Montevideo 11400, Uruguay

[5] Univ Fed Alfenas, Inst Quim, Lab Cristalog, BR-37130000 Alfenas, MG, Brazil

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 100卷

关键词：

Neglected diseases; Trypanosomiasis; Leishmaniasis; Protease; Semicarbazone; Peptide mimetic; TRYPANOSOMA-CRUZI; BIOLOGICAL EVALUATION; CATHEPSIN-L; PERMEABILITY; SOLUBILITY; INHIBITORS; STABILITY; DISCOVERY; THIO;

D O I：

10.1016/j.ejmech.2015.05.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Trypanosomatids are protozoan parasites that cause various diseases in human, such as leishmaniasis, Chagas disease and sleeping sickness. The highly syntenic genomes of the trypanosomatid species lead the assumption that they can encode similar proteins, indicating the possibility to design new antitrypanosomatid drugs with dual trypanosomicidal and leishmanicidal activities. In this work a series of compounds (6a-h and 7a-h), containing a semicarbazone scaffold as a peptide mimetic framework, was designed and synthesized. From this series compound 7g (LASSBio-1483) highlighted, showing dual in vitro trypanosomicidal and leishmanicidal activities, with potency similar to the standard drugs nifurtimox and pentamidine. This data, taken together with its good in silico druglikeness profile and its great chemical and plasma stability, make LASSBio-1483 (7g) a new antitrypanosomatid lead-candidate. (C) 2015 Published by Elsevier Masson SAS.

引用

页码：24 / 33

页数：10

共 42 条

[41] Trypanosoma brucei: Chemical evidence that cathepsin L is essential for survival and a relevant drug target [J].

Steverding, Dietmar ;

Sexton, Darren W. ;

Wang, Xia ;

Gehrke, Sebastian S. ;

Wagner, Gerd K. ;

Caffrey, Conor R. .

INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2012, 42 (05) :481-488

[42] Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants:: Hybrid pharmacophore-based design [J].

Yogeeswari, P ;

Sriram, D ;

Thirumurugan, R ;

Raghavendran, JV ;

Sudhan, K ;

Pavana, RK ;

Stables, J .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (20) :6202-6211

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