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

Lorca, Marcos Muscia, Gisela C. Pérez Benavente, Susana Bautista Santa Cruz, José Manuel Acosta, Alison González, César Sabadini, Gianfranco Mella, Jaime Asís, Silvia E. Mellado, Marco 2024-08-27T07:18:06Z 2024-08-27T07:18:06Z 2024-07-04 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 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. eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International 2D/3D-QSAR Model Development Based on a Quinoline Pharmacophoric Core for the Inhibition of Plasmodium falciparum: An In Silico Approach with Experimental Validation journal article