Five novel metal-based complexes of Ag(Ⅰ)[Ag(ATV)](1),Zn(Ⅱ)[Zn(ATV)_(2)(H_(2)O)_(2)]·2H_(2)O(2),[Zn(ATV)_(2)(CH_(3)OH)_(2)]·H_(2)O(3),{Zn(ATV)_(2)}_(n)(4),and Cu(Ⅱ)[Cu(ATV)_(2)](5),with the antimalarial n...Five novel metal-based complexes of Ag(Ⅰ)[Ag(ATV)](1),Zn(Ⅱ)[Zn(ATV)_(2)(H_(2)O)_(2)]·2H_(2)O(2),[Zn(ATV)_(2)(CH_(3)OH)_(2)]·H_(2)O(3),{Zn(ATV)_(2)}_(n)(4),and Cu(Ⅱ)[Cu(ATV)_(2)](5),with the antimalarial naphthoquinone atovaquone(ATV)were synthesized and characterized.Ag(Ⅰ)and Cu(Ⅱ)complexes were thoroughly analyzed using IR,NMR,EPR,and conductivity measurements,whereas the crystal structures of the three Zn(Ⅱ)complexes were determined by single-crystal X-ray diffraction,supported by complementary analytical techniques.Depending on the metal center,ATV coordinates in either a monodentate or bidentate coordination mode,producing highly stable metal complexes both in the solid state and in DMSO solution.These metal-ATV complexes retain the potent antiplasmodial activity of ATV against chloroquine-sensitive and-resistant Plasmodium falciparum strains and introduce additional mechanisms of action.According to FT IR results,Zn(Ⅱ)complexes inhibit β-hematin formation,complex 3 accelerates ring-stage parasite killing,and complex 5 promotes intracellular copper accumulation,which correlate with enhanced antiplasmodial potency.These results demonstrate that metal coordination can fine-tune the ATV biological profile,positioning these compounds as promising leads for the design of new antimalarial drugs.展开更多
基金funded by the Brazilian agencies:FAPEMIG:APQ-00201-24Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq grants 422821/2025-0 and 440227/2022-4)+7 种基金CAPES(Finance Code 001)the Direction Générale de l’Armement[grant NBC-2-B-2120]the National Research Agency under the“Investments for Future”programme[grant ANR-10-IAHU]the European Regional Development Fund(FEDER)[grant FEDER IHUPERF]support of MCT/FINEP/CT-INFRA(grant no.01/2013-REF 0633/13,coordinated by Prof.M.de Oliveira)FAPESP and the Redoxoma project(grant no.2013/07937-8)for funding the EPR instrumentationPTDC/QUI-QIN/29697/2017 and PTDC/QUI-QIN/3898/2020(2021-2024)support provided by MINDLab(https://www.mindlab.pt)。
文摘Five novel metal-based complexes of Ag(Ⅰ)[Ag(ATV)](1),Zn(Ⅱ)[Zn(ATV)_(2)(H_(2)O)_(2)]·2H_(2)O(2),[Zn(ATV)_(2)(CH_(3)OH)_(2)]·H_(2)O(3),{Zn(ATV)_(2)}_(n)(4),and Cu(Ⅱ)[Cu(ATV)_(2)](5),with the antimalarial naphthoquinone atovaquone(ATV)were synthesized and characterized.Ag(Ⅰ)and Cu(Ⅱ)complexes were thoroughly analyzed using IR,NMR,EPR,and conductivity measurements,whereas the crystal structures of the three Zn(Ⅱ)complexes were determined by single-crystal X-ray diffraction,supported by complementary analytical techniques.Depending on the metal center,ATV coordinates in either a monodentate or bidentate coordination mode,producing highly stable metal complexes both in the solid state and in DMSO solution.These metal-ATV complexes retain the potent antiplasmodial activity of ATV against chloroquine-sensitive and-resistant Plasmodium falciparum strains and introduce additional mechanisms of action.According to FT IR results,Zn(Ⅱ)complexes inhibit β-hematin formation,complex 3 accelerates ring-stage parasite killing,and complex 5 promotes intracellular copper accumulation,which correlate with enhanced antiplasmodial potency.These results demonstrate that metal coordination can fine-tune the ATV biological profile,positioning these compounds as promising leads for the design of new antimalarial drugs.
