2026-06-03T19:14:36Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1076922025-03-18T14:09:08Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Lorca, Marcos author Muscia, Gisela C. author Pérez Benavente, Susana author Bautista Santa Cruz, José Manuel author Acosta, Alison author González, César author Sabadini, Gianfranco author Mella, Jaime author Asís, Silvia E. author Mellado, Marco author 2024-07-04 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. 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 10.3390/ph17070889 https://hdl.handle.net/20.500.14352/107692 1424-8247 https://doi.org/10.3390/ph17070889 2D/3D-QSAR Model Development Based on a Quinoline Pharmacophoric Core for the Inhibition of Plasmodium falciparum: An In Silico Approach with Experimental Validation