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This growing resistance has compromised the efficacy of frontline treatments and has led to the disease continuing to claim thousands of lives each year. Consequently, a new effective and non-toxic anti-malarial drug is urgently needed. In this context, metal\u2013NHC (\n                      <jats:italic>N<\/jats:italic>\n                      -heterocyclic carbene) complexes have diverse physicochemical properties that could enhance biological activity and lead to the development of a new drug to combat malaria. On this regard, this study examined the biological activity of two metal\u2013NHC complexes and their NHC precursor in two strains of the parasite,\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      (3D7 and FCR-3), with specific targets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The synthesis of all metal\u2013NHC complexes was carried out under nitrogen atmosphere using Schlenk techniques. We studied the biological activity of two metal\u2013NHC complexes and their NHC precursor in two\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      strains (3D7 and FCR-3) and the selectivity index. Additionally, the possible interactions of these metal compounds with specific targets were evaluated. These targets included reactive oxygen species (ROS), albumin (BSA), Fe(III) PPIX, and \u03b2-hematin. The evaluation also included lipophilicity and ADMET properties. These properties were evaluated through diverse physical and spectroscopic methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The IC\n                      <jats:sub>50<\/jats:sub>\n                      values of the NHC precursor (\n                      <jats:bold>L<\/jats:bold>\n                      ) and the two metal\u2013NHC complexes (\n                      <jats:bold>1<\/jats:bold>\n                      and\n                      <jats:bold>2<\/jats:bold>\n                      ) were similar in\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      chloroquine-sensitive and -resistant strains. They showed a higher selectivity index than chloroquine and do not cause hemolysis in red blood cells. Additionally, the compounds have a dose-dependent effect on the progression of the\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      erythrocytic cycle, resulting in the accumulation of ring and trophozoite forms at high concentrations in the FCR-3 strain. These compounds may alter the pH of acidic organelles in the cytosol of the parasite, such as the digestive vacuole and the accessory vacuoles. Compounds\n                      <jats:bold>L<\/jats:bold>\n                      ,\n                      <jats:bold>1<\/jats:bold>\n                      and\n                      <jats:bold>2<\/jats:bold>\n                      are capable to generate reactive oxygen species (ROS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Preliminary studies reported in this paper suggest that the two metal\u2013NHC complexes\n                      <jats:bold>1<\/jats:bold>\n                      and\n                      <jats:bold>2<\/jats:bold>\n                      interact with targets such as the inhibition of \u03b2-hematin and the production of reactive oxygen species (ROS). They also have lipophilic and physicochemical profiles that correlate with their antiplasmodial efficacy. Both complexes exhibit moderate activity, indicating potential for further evaluation. A plausible explanation is that this behavior arises from the nature of both the ligand and the metal center. Accordingly, these initial findings provide a basis for the further exploration of new antimalarial compounds.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12936-026-05944-7","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:36:39Z","timestamp":1781069799000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Searching for new candidates for antimalarial therapy: physicochemical and in vitro evaluation of gold(I) and silver(I) N-heterocyclic carbene complexes"],"prefix":"10.1186","volume":"25","author":[{"given":"William","family":"Castro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector R.","family":"Rangel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liseth","family":"Garibaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma","family":"Rojas-Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Jos\u00e9","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Berroteran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriel","family":"Sanchez-Velasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Cristina","family":"Goite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Coll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Hidalgo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"5944_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.1797","volume":"7","author":"MO Oduoye","year":"2024","unstructured":"Oduoye MO, Haider MU, Marsool MDM, Kareem MO, Adedayo AE, Abdulkarim AS, et al. 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