A Potent N-(piperidin-4-yl)-1H-pyrrole-2-carboxamide Inhibitor of Adenylyl Cyclase of G. lamblia: Biological Evaluation and Molecular Modelling Studies

被引：1

作者：

Vega Hissi, Esteban G. ^{[1
]}

De Costa Guardamagna, Antonella B. ^{[1
]}

Garro, Adriana D. ^{[1
]}

Falcon, Cristian R. ^{[1
]}

Anderluh, Marko ^{[2
]}

Tomasic, Tihomir ^{[2
]}

Kikelj, Danijel ^{[2
]}

Yaneff, Agustin ^{[3
]}

Davio, Carlos A. ^{[3
]}

Enriz, Ricardo D. ^{[1
]}

Zurita, Adolfo R. ^{[1
]}

机构：

[1] Univ Nacl San Luis, Fac Quim Bioquim & Farm, Inst Multidisciplinario Invest Biol IMIBIO SL, Ejercito Los Andes 950, RA-5700 San Luis, Argentina

[2] Univ Ljubljana, Dept Med Chem, Fac Pharm, Askerceva Cesta 7, Ljubljana 1000, Slovenia

[3] Univ Buenos Aires, Fac Farm & Bioquim, Inst Invest Farmacol ININFA UBA CONICET, Junin 956,C1113AAD, Buenos Aires, DF, Argentina

来源：

CHEMMEDCHEM | 2021年 / 16卷 / 13期

关键词：

Adenylyl cyclase inhibitors; cAmp; G; lamblia; Molecular medicine; Molecular modelling; PROTEIN-KINASE-A; EARLY DIVERGING EUKARYOTE; GIARDIA-LAMBLIA; CYCLIC-AMP; FUNCTIONAL-CHARACTERIZATION; CRYSTAL-STRUCTURE; BINDING; CAMP; ACTIVATION; 2-HYDROXYESTRADIOL;

D O I：

10.1002/cmdc.202100037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this work, we report a derivative of N-(piperidin-4-yl)-1H-pyrrole-2-carboxamide as a new inhibitor for adenylyl cyclase of Giardia lamblia which was obtained from a study using structural data of the nucleotidyl cyclase 1 (gNC1) of this parasite. For such a study, we developed a model for this specific enzyme by using homology techniques, which is the first model reported for gNC1 of G. lamblia. Our studies show that the new inhibitor has a competitive mechanism of action against this enzyme. 2-Hydroxyestradiol was used as the reference compound for comparative studies. Results in this work are important from two points of view. on the one hand, an experimentally corroborated model for gNC1 of G. lamblia obtained by molecular modelling is presented; on the other hand, the new inhibitor obtained is an undoubtedly excellent starting structure for the development of new metabolic inhibitors for G. lamblia.

引用

页码：2094 / 2105

页数：12

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