biostudies-literatureUnknown14(10)Gianibbi B<b>Background/Objectives</b>: Malaria remains the most critical parasitic disease globally, responsible for over 600.000 deaths annually. In sub-Saharan Africa, co-infections of <i>Plasmodium falciparum</i> with other pathogens, particularly <i>Staphylococcus aureus</i>, are common in children with severe malaria. Therefore, the design of new compounds targeting both pathogens appears to be an urgent priority. <b>Methods</b>: A small series of hybrid compounds was designed and synthesized by linking the pharmacophore of the antimalarial drug chloroquine with the phenothiazine core. These compounds were tested in vitro against a panel of microbial strains and further analyzed through in silico simulations to predict their physical-chemical properties. <b>Results</b>: Compounds <b>4b</b> andAntibiotics (Basel, Switzerland)991https://www.ebi.ac.uk/biostudies/studies/S-EPMC12561106biostudies-literatureSTOP Strategy to Inhibit <i>P. falciparum</i> and <i>S. aureus</i> Growth: Molecular Mechanism Studies on Purposely Designed Hybrids.PMC12561106Gentilomi GABonvicini FGobbi SBelluti FBisi ABasilico NParapini SCorina RGianibbi BSpiga OfalseSTOP Strategy to Inhibit <i>P. falciparum</i> and <i>S. aureus</i> Growth: Molecular Mechanism Studies on Purposely Designed Hybrids.<b>Background/Objectives</b>: Malaria remains the most critical parasitic disease globally, responsible for over 600.000 deaths annually. In sub-Saharan Africa, co-infections of <i>Plasmodium falciparum</i> with other pathogens, particularly <i>Staphylococcus aureus</i>, are common in children with severe malaria. Therefore, the design of new compounds targeting both pathogens appears to be an urgent priority. <b>Methods</b>: A small series of hybrid compounds was designed and synthesized by linking the pharmacophore of the antimalarial drug chloroquine with the phenothiazine core. These compounds were tested in vitro against a panel of microbial strains and further analyzed through in silico simulations to predict their physical-chemical properties. <b>Results</b>: Compounds <b>4b</b> and2025-01-01T00:00:00Z2025 Oct2026-05-15T03:18:24.856Z2026-05-15T03:12:26.05ZS-EPMC125611064114868310.3390/antibiotics14100991