Integrative lipophilicity assessment and pharmacokinetic correlation of pyrimidine precursors and artesunate–pyrimidine hybrids: development of QSAR models for anticancer activity and interaction with P -glycoprotein

Lipophilicity and steric/electronic descriptors govern distribution, protein binding, and anticancer activity. Integrating these features enables design of hybrids overcoming P-gp-mediated multidrug resistance, with hybrid 4k emerging as a promising candidate.