{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T10:44:20Z","timestamp":1784371460085,"version":"3.55.0"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI-102254"],"award-info":[{"award-number":["AI-102254"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"MINCyT | Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2012 #0457"],"award-info":[{"award-number":["PICT 2012 #0457"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PIP 0797"],"award-info":[{"award-number":["PIP 0797"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["20020130100223BA"],"award-info":[{"award-number":["20020130100223BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bisphosphonates are widely used for the treatment of bone disorders. These drugs also inhibit the growth of a variety of protozoan parasites, such as\n            <jats:named-content content-type=\"genus-species\">Toxoplasma gondii<\/jats:named-content>\n            , the etiologic agent of toxoplasmosis. The target of the most potent bisphosphonates is the isoprenoid biosynthesis pathway enzyme farnesyl diphosphate synthase (FPPS). Based on our previous work on the inhibitory effect of sulfur-containing linear bisphosphonates against\n            <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n            , we investigated the potential synergistic interaction between one of these derivatives, 1-[(\n            <jats:italic>n<\/jats:italic>\n            -heptylthio)ethyl]-1,1-bisphosphonate (C7S), and statins, which are potent inhibitors of the host 3-hydroxy-3-methyl glutaryl-coenzyme A reductase (3-HMG-CoA reductase). C7S showed high activity against the\n            <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n            bifunctional farnesyl diphosphate (FPP)\/geranylgeranyl diphosphate (GGPP) synthase (TgFPPS), which catalyzes the formation of FPP and GGPP (50% inhibitory concentration [IC\n            <jats:sub>50<\/jats:sub>\n            ] = 31 \u00b1 0.01 nM [mean \u00b1 standard deviation]), and modest effect against the human FPPS (IC\n            <jats:sub>50<\/jats:sub>\n            = 1.3 \u00b1 0.5 \u03bcM). We tested combinations of C7S with statins against the\n            <jats:italic>in vitro<\/jats:italic>\n            replication of\n            <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n            . We also treated mice infected with a lethal dose of\n            <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n            with similar combinations. We found strong synergistic activities when using low doses of C7S, which were stronger\n            <jats:italic>in vivo<\/jats:italic>\n            than when tested\n            <jats:italic>in vitro<\/jats:italic>\n            . We also investigated the synergism of several commercially available bisphosphonates with statins both\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            . Our results provide evidence that it is possible to develop drug combinations that act synergistically by inhibiting host and parasite enzymes\n            <jats:italic>in vitro<\/jats:italic>\n            and in\n            <jats:italic>vivo<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.02628-16","type":"journal-article","created":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T00:40:34Z","timestamp":1496191234000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Synergistic Activity between Statins and Bisphosphonates against Acute Experimental Toxoplasmosis"],"prefix":"10.1128","volume":"61","author":[{"given":"Zhu-Hong","family":"Li","sequence":"first","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio H.","family":"Szajnman","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan B.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia N. 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