{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:45:51Z","timestamp":1788911151920,"version":"build-2803163510"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001688","name":"International Centre for Genetic Engineering and Biotechnology","doi-asserted-by":"publisher","award":["CRP\/22\/005"],"award-info":[{"award-number":["CRP\/22\/005"]}],"id":[{"id":"10.13039\/501100001688","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Human Resource Development Group-Council of Scientific and Industrial Research"},{"name":"Indian Institute of Technology Bombay-Monash Research Academy"},{"name":"Department of Biotechnology (DBT), India"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nuclear import, dependent on the transporter importin \u03b1 (IMP\u03b1), is a drug target for apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii. Indeed, a panel of small molecule inhibit interactions between IMP\u03b1 and nuclear localization signals (NLSs) in vitro and the growth of rapidly dividing stages (P. falciparum blood stages and T. gondii tachyzoites) in culture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>As new drugs targeting multiple life cycle stages of both parasites are required, the panel of IMP\u03b1 inhibitors was tested for their ability to inhibit nuclear transport in the rapidly dividing stages and the maturation of differentiated stages (P. falciparum gametocytes and T. gondii bradyzoites).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using biophysical assays, Bay 11-7082, a Bay 11-7085 structural analogue, was tested for inhibition of IMP\u03b1:NLS interactions. The effect of the panel of inhibitors on the nuclear localization of reporter proteins was analysed in both parasites using transfections and microscopy. Also, using microscopy, the effect of inhibitors on differentiated stages of both parasites was tested.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bay 11-7085 can inhibit nuclear transport in tachyzoites, while GW5074 and Caffeic Acid Phenethyl Ester (CAPE) can inhibit nuclear transport in the blood stages. Interestingly, CAPE can strongly inhibit gametocyte maturation, and Bay 11-7082 and Bay 11-7085 weakly inhibit bradyzoite differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>As differentiation of gametocytes and bradyzoites is dependent on the activation of gene expression triggered by the nuclear translocation of transcription factors, our work provides a \u2018proof of concept\u2019 that targeting nuclear import is a viable strategy for the development of therapeutics against multiple stages of apicomplexan parasites, some of which are recalcitrant to existing drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkae434","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T15:30:13Z","timestamp":1732289413000},"page":"485-495","source":"Crossref","is-referenced-by-count":2,"title":["Importin \u03b1 inhibitors act against the differentiated stages of apicomplexan parasites\n                    <i>Plasmodium falciparum<\/i>\n                    and\n                    <i>Toxoplasma gondii<\/i>"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7146-4027","authenticated-orcid":false,"given":"Manasi","family":"Bhambid","sequence":"first","affiliation":[{"name":"Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujata B","family":"Walunj","sequence":"additional","affiliation":[{"name":"Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]},{"name":"Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University , Clayton ,","place":["Australia"]},{"name":"IITB-Monash Research Academy, IIT Bombay , Mumbai 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