Bibliographic citations
Medina, F., Vasquez, C. (2022). Búsqueda de potenciales inhibidores de HSP90 de P. falciparum mediante tamizaje virtual basado en farmacóforos [Tesis, Universidad Peruana de Ciencias Aplicadas (UPC)]. http://hdl.handle.net/10757/667390
Medina, F., Vasquez, C. Búsqueda de potenciales inhibidores de HSP90 de P. falciparum mediante tamizaje virtual basado en farmacóforos [Tesis]. PE: Universidad Peruana de Ciencias Aplicadas (UPC); 2022. http://hdl.handle.net/10757/667390
@misc{renati/1293875,
title = "Búsqueda de potenciales inhibidores de HSP90 de P. falciparum mediante tamizaje virtual basado en farmacóforos",
author = "Vasquez Marin, Christina Nikole",
publisher = "Universidad Peruana de Ciencias Aplicadas (UPC)",
year = "2022"
}
Introduction: Malaria represents one of the biggest public health problems. The growing drug resistance makes it necessary to search for new pharmacotherapeutic alternatives. Plasmodium falciparum heat shock protein HSP90 (pfHSP90) emerges as an important therapeutic target due to its role in cell regulation processes essential for parasite survival. Objective: To design, refine and evaluate in silico pharmacophoric models for the search for potential inhibitors of the pfHSP90 protein through the use of a massive screening platform. Methods: In silico experimental research. A molecular docking protocol was developed and validated. Then, two pharmacophoric models were designed using the three-dimensional information of the receptor. The models were refined and validated using active and inactive molecules against pfHSP90. Finally, a massive virtual screening was performed using the models Results: Pharmacophoric models C and D were obtained. Both models presented "excellent" theoretical validation parameters according to the literature (for C Se: 1, Sp: 0.958 and AUC-ROC: 1.0; for D Se: 1, Sp: 1 and AUC-ROC: 1.0). As a result of the massive virtual screening of ChEMBL 21 database of 1578014 molecules, 06 hits were obtained which, after being analyzed, were reduced to 04 potential inhibitors. Conclusions: Two pharmacophoric models for family C and D compounds were designed, optimized, validated, and evaluated in silico through the structure-based approach. Subsequently, due to massive virtual screening, 04 potential inhibitors of the pfHSP90 protein were identified.
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