Poster Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Zinc-Antimalarial drug Complexes: Synthesis, Characterization, Antimalarial Activity and Mechanism of Action. (#451)

Maribel Navarro 1 , Luana Daniel 1 , Giovana Pimentel 1 , Bruno Pradini 2 , Diogo Moreira 3
  1. Chemistry, Federal University of Juiz de Fora, Juiz De Fora, MINAS GERAIS, Brazil
  2. Unité Parasitologie et entomologie, , Institut de recherche biomédicale des armées,, Marseille, France
  3. Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil

Malaria remains a major global public health threat. In 2023, an estimated 263 million cases were reported, which resulted in 597,000 deaths worldwide[1]. The antimalarial activity of Zinc-based complexes has not  been widely studies, but this can be an untapped source of effective drugs against this disease[2]. Zn complexes of antimalarial drugs, such as : [ZnAQCl2] (1), [ZnAQ(OH)2] (2), [ZnCQCl2] (3), [Zn(AQ)(AcO)2] (4) and [Zn(ATV)2(H2O)2] (5), [Zn(ATV)2(CH3OH)2]-H2O (6) [Zn(ATV)2]n (7) were synthesized by coordination of amodiaquine (AQ), chloroquine (CQ) and atovaquone (ATV) to the precursors ZnX2-2H2O (where X= Cl- or AcO-) under mild conditions and in good yields. They have been fully characterized in solid state and solution by various analytical spectroscopic techniques, and some of the structures were also confirmed by X-ray diffraction[3]. These compounds (1-7) showed high stability both in the solid state and solution. Their interaction with ferriprotoporphyrin (FePPIX) was similar to chloroquine (k= 5.15)[4] based on the log K values (log K = 4.14 (1); 4.05 (2); 5.48 (3); 5.71 (4); 4.14 (5); 4.68 (6); 4.49 (7) respectively). DNA studies were performed using spectroscopic titration, viscosity and electrophoresis. They interacted with DNA by reversible interaction, The interaction constant (Kb) was higher than the 10³, revealing that compounds 1, 2, 5, 6 and 7 interacted with DNA through the major groove while the corresponding free ligands, ATV, AQ and CQ interacted by intercalation via the minor groove[4]. In vitro antimalarial activity was evaluated against Plasmodium falciparum using the chloroquine-resistant strain (W2). Each compound had the IC50 values in the nanomolar range, complex 2 being the most active (7 nM) . In summary, compound 2 has demonstrated significant potential for the development of new antimalarial agents effective against chloroquine-resistant strains.

 

Acknowledgments: FAPEMIG/APQ-00201-24, CNPq /306351/2023-4 and CAPES

  1. References [1] WHO. World Malaria Report 2024 [2] M. Navarro, L. Daniel, L. Colina-Vegas, G. Visbal. Zinc from an Essential Element to an Antiparasitic Therapeutic Agent. ACS Omega. 10, 2393−2414, 2025. [3] L. Daniel, A. Karam, C. H. J. Franco, C. Conde, A. Sacramento de Morais, J. Mosnier, I. Fonta, W. Villarreal, B. Pradines, D. Rodrigo M. Moreira, M. Navarro. Inorg. Chem. 63, 17087-17099, 2024. [4] G. Y. Sánchez Delgado, M. Navarro. An overview of auric compounds as antimalarial agents and their action against essential targets of the parasite. Coordination Chemistry Reviews, v. 503, 215633, 2024.