RT Journal Article
T1 2D/3D-QSAR Model Development Based on a Quinoline Pharmacophoric Core for the Inhibition of Plasmodium falciparum: An In Silico Approach with Experimental Validation
A1 Lorca, Marcos
A1 Muscia, Gisela C.
A1 Pérez Benavente, Susana
A1 Bautista Santa Cruz, José Manuel
A1 Acosta, Alison
A1 González, César
A1 Sabadini, Gianfranco
A1 Mella, Jaime
A1 Asís, Silvia E.
A1 Mellado, Marco
AB Malaria is an infectious disease caused by Plasmodium spp. parasites, with widespread drug resistance to most antimalarial drugs. We report the development of two 3D-QSAR models based on comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and a 2D-QSAR model, using a database of 349 compounds with activity against the P. falciparum 3D7 strain. The models were validated internally and externally, complying with all metrics (q2 > 0.5, r2test > 0.6, r2m > 0.5, etc.). The final models have shown the following statistical values: r2test CoMFA = 0.878, r2test CoMSIA = 0.876, and r2test 2D-QSAR = 0.845. The models were experimentally tested through the synthesis and biological evaluation of ten quinoline derivatives against P. falciparum 3D7. The CoMSIA and 2D-QSAR models outperformed CoMFA in terms of better predictive capacity (MAE = 0.7006, 0.4849, and 1.2803, respectively). The physicochemical and pharmacokinetic properties of three selected quinoline derivatives were similar to chloroquine. Finally, the compounds showed low cytotoxicity (IC50 > 100 µM) on human HepG2 cells. These results suggest that the QSAR models accurately predict the toxicological profile, correlating well with experimental in vivo data.
PB MDPI
YR 2024
FD 2024-07-04
LK https://hdl.handle.net/20.500.14352/107692
UL https://hdl.handle.net/20.500.14352/107692
LA eng
NO Lorca, M.; Muscia, G.C.; Pérez-Benavente, S.; Bautista, J.M.; Acosta, A.; González, C.; Sabadini, G.; Mella, J.; Asís, S.E.; Mellado, M. 2D/3D-QSAR Model Development Based on a Quinoline Pharmacophoric Core for the Inhibition of Plasmodium falciparum: An In Silico Approach with Experimental Validation. Pharmaceuticals 2024, 17, 889. https://doi.org/10.3390/ph17070889
NO Beca Anid-PFCHA/Doctorado Nacional/2018-21180427Beca Anid ID 16649FONDECYT, grant number 1240289PROYECTO PUENTE UVA 22991
NO Agencia Nacional de Investigación y Desarrollo (ANID)
NO Universidad de Valparaíso (Chile)
DS Docta Complutense
RD 25 may 2025