{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:57:46Z","timestamp":1770839866065,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Malaria, a life-threatening mosquito-borne disease caused by Plasmodium parasites, continues to pose a significant global health burden. Despite notable progress in combating the disease in recent years, malaria remains prevalent in many regions, particularly in Southeast Asia and most of sub-Saharan Africa, where it claims hundreds of thousands of lives annually. Flavonoids, such as the baicalein class of compounds, are known to have antimalarial properties. In this study, we rationally designed and synthesized a series of baicalein derivatives and identified a lead compound, FNDR-10132, that displayed potent in vitro antimalarial activity against Plasmodium falciparum (P. falciparum), both chloroquine-sensitive (60 nM) and chloroquine-resistant (177 nM) parasites. FNDR-10132 was evaluated for its antimalarial activity in vivo against the chloroquine-resistant strain Plasmodium yoelii N67 in Swiss mice. The oral administration of 100 mg\/kg of FNDR-10132 showed 44% parasite suppression on day 4, with a mean survival time of 13.5 \u00b1 2.3 days vs. 8.4 \u00b1 2.3 days of control. Also, FNDR-10132 displayed equivalent activity against the resistant strains of P. falciparum in the 200\u2013300 nM range. This study offers a novel series of antimalarial compounds that could be developed into potent drugs against chloroquine-resistant malarial parasites through further chemistry and DMPK optimization.<\/jats:p>","DOI":"10.3390\/pathogens12101242","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T10:04:39Z","timestamp":1697191479000},"page":"1242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel Baicalein-Derived Inhibitors of Plasmodium falciparum"],"prefix":"10.3390","volume":"12","author":[{"given":"Chandra Sekhar","family":"Gudla","sequence":"first","affiliation":[{"name":"Foundation for Neglected Disease Research, Bangalore 561203, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0187-7293","authenticated-orcid":false,"given":"Vignesh","family":"Selvam","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research, Bangalore 561203, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9188-8276","authenticated-orcid":false,"given":"Siva Shanmugam","family":"Selvaraj","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research, Bangalore 561203, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renu","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Immunology, CSIR\u2014Central Drug Research Institute, Lucknow 226301, Uttar Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prince","family":"Joshi","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Immunology, CSIR\u2014Central Drug Research Institute, Lucknow 226301, Uttar Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salique Hassan","family":"Shaham","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Immunology, CSIR\u2014Central Drug Research Institute, Lucknow 226301, Uttar Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayas","family":"Singh","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research, Bangalore 561203, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-1340","authenticated-orcid":false,"given":"Radha Krishan","family":"Shandil","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research, Bangalore 561203, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saman","family":"Habib","sequence":"additional","affiliation":[{"name":"Biochemistry and Structural Biology, CSIR\u2014Central Drug Research Institute, Lucknow 226301, Uttar Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shridhar","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research, Bangalore 561203, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lehane, A.M., and Saliba, K.J. 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