A Potent N-(piperidin-4-yl)-1H-pyrrole-2-carboxamide Inhibitor of Adenylyl Cyclase of G. lamblia: Biological Evaluation and Molecular Modelling Studies |
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| Authors: | Dr Esteban G Vega Hissi Antonella B De Costa Guardamagna Dr Adriana D Garro Dr Cristian R Falcon Dr Marko Anderluh Dr Tihomir Tomašič Dr Danijel Kikelj Dr Agustín Yaneff Dr Carlos A Davio Dr Ricardo D Enriz Dr Adolfo R Zurita |
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| Affiliation: | 1. Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Instituto Multidisciplinario de Investigaciones Biológicas (IMIBIO-SL), Ejército de los Andes 950, 5700 San Luis, Argentina;2. Department of Medicinal Chemistry, University of Ljubljana, Faculty of Pharmacy Askerceva, cesta 7, 1000 Ljubljana, Slovenia;3. Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113 AAD, Buenos Aires, Argentina |
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| Abstract: | 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. |
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| Keywords: | Adenylyl cyclase inhibitors cAmp G lamblia Molecular medicine Molecular modelling |
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