Thiosemicarbazones derived from 1-indanones as new anti-Trypanosoma cruzi agents

被引：53

作者：

Caputto, Maria E. ^{[2
]}

Fabian, Lucas E. ^{[2
]}

Benitez, Diego ^{[1
]}

Merlino, Alicia ^{[1
,4
]}

Rios, Natalia ^{[1
]}

Cerecetto, Hugo ^{[1
]}

Moltrasio, Graciela Y. ^{[3
]}

Moglioni, Albertina G. ^{[2
]}

Gonzalez, Mercedes ^{[1
]}

Finkielsztein, Liliana M. ^{[2
]}

机构：

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

[2] Univ Buenos Aires, Dept Farmacol, Fac Farm & Bioquim, RA-1113 Buenos Aires, DF, Argentina

[3] Univ Buenos Aires, Dept Quim Organ, Fac Farm & Bioquim, RA-1113 Buenos Aires, DF, Argentina

[4] Univ Republica, Fac Ciencias, Lab Quim Teor & Computac, Montevideo 11400, Uruguay

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 22期

关键词：

Thiosemicarbazones; 1-Indanones; Chagas' disease; Anti-Trypanosoma cruzi agents; Microwave-assisted synthesis; Cruzipain; IN-VITRO; CYSTEINE PROTEASE; BINDING-SITES; COMPLEXES; DERIVATIVES; VIVO; 5-NITROFURYL; INHIBITORS; DOCKING; SEARCH;

D O I：

10.1016/j.bmc.2011.09.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

In the present work, we synthesized a series of thiosemicarbazones derived from 1-indanones with good anti-Trypanosoma cruzi activity. Most of them displayed remarkable trypanosomicidal activity. All the compounds showed nonspecific cytotoxicity on human erythrocytes. The ability of the new compounds to inhibit cruzipain, the major cysteine protease of T. cruzi, was also explored. Thiosemicarbazones 12 and 24 inhibited this enzyme at the dose assayed. This interaction was also studied in terms of molecular docking. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：6818 / 6826

页数：9

共 46 条

[1]

In vitro activity and mechanism of action against the protozoan parasite Trypanosoma cruzi of 5-nitrofuryl containing thiosemicarbazones [J].

Aguirre, G ;

Boiani, L ;

Cerecetto, H ;

Fernández, M ;

González, M ;

Denicola, A ;

Otero, L ;

Gambino, D ;

Rigol, C ;

Olea-Azar, C ;

Faundez, M .

BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (18) :4885-4893

[2]

Trypanosoma cruzi:: Characterization of an intracellular epimastigote-like form [J].

Almeida-de-Faria, M ;

Freymüller, E ;

Colli, W ;

Alves, MJM .

EXPERIMENTAL PARASITOLOGY, 1999, 92 (04) :263-274

[3]

[Anonymous], 2002, WHO TECH REP SER, V905, P1

[4]

In vivo studies of 5-arylethenylbenzofuroxans in acute murine models of Chagas' disease [J].

Boiani, Lucia ;

Davies, Carolina ;

Arredondo, Carolina ;

Porcal, Williams ;

Merlino, Alicia ;

Gerpe, Alejandra ;

Boiani, Mariana ;

Pacheco, Jose Pedro ;

Basombrio, Miguel Angel ;

Cerecetto, Hugo ;

Gonzalez, Mercedes .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2008, 43 (10) :2229-2237

[5]

In vitro and in vivo antitrypanosomatid activity of 5-nitroindazoles [J].

Boiani, Lucia ;

Gerpe, Alejandra ;

Aran, Vicente J. ;

Torres de Ortiz, Susana ;

Serna, Elva ;

Vera de Bilbao, Ninfa ;

Sanabria, Luis ;

Yaluff, Gloria ;

Nakayama, Hector ;

Rojas de Arias, Antonieta ;

Diego Maya, Juan ;

Antonio Morello, J. ;

Cerecetto, Hugo ;

Gonzalez, Mercedes .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (03) :1034-1040

[6]

2H-benzimidazole 1,3-dioxide derivatives:: A new family of water-soluble anti-trypanosomatid agents [J].

Boiani, Mariana ;

Boiani, Lucia ;

Denicola, Ana ;

Torres de Ortiz, Susana ;

Serna, Elva ;

Vera de Bilbao, Ninfa ;

Sanabria, Luis ;

Yaluff, Gloria ;

Nakayama, Hector ;

Rojas de Arias, Antonieta ;

Vega, Celeste ;

Rolan, Miriam ;

Gomez-Barrio, Alicia ;

Cerecetto, Hugo ;

Gonzalez, Mercedes .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (11) :3215-3224

[7]

Redirection of the Immune Response to the Functional Catalytic Domain of the Cystein Proteinase Cruzipain Improves Protective Immunity against Trypanosoma cruzi Infection [J].

Cazorla, Silvia I. ;

Frank, Fernanda M. ;

Becker, Pablo D. ;

Arnaiz, Maria ;

Mirkin, Gerardo A. ;

Corral, Ricardo S. ;

Guzman, Carlos A. ;

Malchiodi, Emilio L. .

JOURNAL OF INFECTIOUS DISEASES, 2010, 202 (01) :136-144

[8]

Cazzulo Juan Jose, 2002, Current Topics in Medicinal Chemistry, V2, P1261, DOI 10.2174/1568026023392995

[9]

Synthetic Medicinal Chemistry in Chagas' Disease: Compounds at The Final Stage of "Hit-To-Lead" Phase [J].

Cerecetto, Hugo ;

Gonzalez, Mercedes .

PHARMACEUTICALS, 2010, 3 (04) :810-838

[10]

VALIDATION OF THE GENERAL-PURPOSE TRIPOS 5.2 FORCE-FIELD [J].

CLARK, M ;

CRAMER, RD ;

VANOPDENBOSCH, N .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1989, 10 (08) :982-1012

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