{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T18:32:58Z","timestamp":1792348378368,"version":"4.4.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100007708","name":"Fondo Nacional de Ciencia Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["2017000724"],"award-info":[{"award-number":["2017000724"]}],"id":[{"id":"10.13039\/501100007708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007708","name":"Fondo Nacional de Ciencia Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["Venezuela"],"award-info":[{"award-number":["Venezuela"]}],"id":[{"id":"10.13039\/501100007708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006434","name":"Consejo de Desarrollo Cient\u00edfico y Human\u00edstico, Universidad Central de Venezuela","doi-asserted-by":"publisher","award":["PG 03-8728-2013\/2"],"award-info":[{"award-number":["PG 03-8728-2013\/2"]}],"id":[{"id":"10.13039\/501100006434","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":[[2018,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Leishmania donovani<\/jats:named-content>\n            is the causing agent of visceral leishmaniasis, a common infection that affects millions of people from the most underdeveloped countries. Miltefosine is the only oral drug to treat infections caused by\n            <jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>\n            . Nevertheless, its mechanism of action is not well understood. While miltefosine inhibits the synthesis of phosphatidylcholine and also affects the parasite mitochondrion, inhibiting the cytochrome\n            <jats:italic>c<\/jats:italic>\n            oxidase, it is to be expected that this potent drug also produces its effect through other targets. In this context, it has been reported that the disruption of the intracellular Ca\n            <jats:sup>2+<\/jats:sup>\n            homeostasis represents an important object for the action of drugs in trypanosomatids. Recently, we have described a plasma membrane Ca\n            <jats:sup>2+<\/jats:sup>\n            channel in\n            <jats:named-content content-type=\"genus-species\">Leishmania mexicana<\/jats:named-content>\n            , which is similar to the L-type voltage-gated Ca\n            <jats:sup>2+<\/jats:sup>\n            channel (VGCC) present in humans. Remarkably, the parasite Ca\n            <jats:sup>2+<\/jats:sup>\n            channel is activated by sphingosine, while the L-type VGCC is not affected by this sphingolipid. In the present work we demonstrated that, similarly to sphingosine, miltefosine is able to activate the plasma membrane Ca\n            <jats:sup>2+<\/jats:sup>\n            channel from\n            <jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>\n            . Interestingly, nifedipine, the classical antagonist of the human channel, was not able to fully block the parasite plasma membrane Ca\n            <jats:sup>2+<\/jats:sup>\n            channel, indicating that the mechanism of interaction is not identical to that of sphingosine. In this work we also show that miltefosine is able to strongly affect the acidocalcisomes from\n            <jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>\n            , inducing the rapid alkalinization of these important organelles. In conclusion, we demonstrate two new mechanisms of action of miltefosine in\n            <jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>\n            , both related to disruption of parasite Ca\n            <jats:sup>2+<\/jats:sup>\n            homeostasis.\n          <\/jats:p>","DOI":"10.1128\/aac.01614-17","type":"journal-article","created":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T00:40:25Z","timestamp":1508805625000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":94,"title":["Mechanism of Action of Miltefosine on Leishmania donovani Involves the Impairment of Acidocalcisome Function and the Activation of the Sphingosine-Dependent Plasma Membrane Ca\n            <sup>2+<\/sup>\n            Channel"],"prefix":"10.1128","volume":"62","author":[{"given":"Andrea K.","family":"Pinto-Martinez","sequence":"first","affiliation":[{"name":"Instituto de Estudios Avanzados 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