{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:01:37Z","timestamp":1780084897394,"version":"3.54.0"},"reference-count":45,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013987","name":"Kenyan government","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013987","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Apothekerstiftung Westfalen-Lippe"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Molecules"],"abstract":"<jats:p>Human African Trypanosomiasis (HAT; sleeping sickness) and Malaria are life-threatening protozoan infections in tropical regions, with limited treatment options. As part of our ongoing efforts to discover new aminosteroid alkaloids from the Buxaceae family with antiprotozoal activity, which might serve as leads to new drugs against these infections, we investigated the dichloromethane extract from the leaves of Buxus obtusifolia (Mildbr.) Hutch. collected in Kenya, a species native to Kenya and Tanzania. To the best of our knowledge, and based on the most recent comprehensive literature review, this study represents the first phytochemical investigation of this plant. The alkaloid-enriched fraction yielded a total of 24 aminosteroid alkaloids, including 18 hitherto undescribed compounds (2, 3, 5\u20139, 11, 12, 15\u201319, and 21\u201324), along with six known compounds, two of which (1 and 4) are described as constituents of a natural source for the first time. Obtusiaminocyclin (24) represents the first Buxus alkaloid with a novel carbocyclic steroid skeleton with a cyclopropane ring comprising C-9, C-19 and C-11 accompanied by an unprecedented amino bridge between C-3 and C-10. The structures of the isolated compounds were determined using UHPLC\/+ESI-QqTOF-MS\/MS and NMR spectroscopy. The total crude extract, the alkaloid-enriched fraction, CPC subfractions and all isolated compounds were tested for in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense (Tbr, responsible for East African HAT) and Plasmodium falciparum (Pf, responsible for tropical Malaria) as well as cytotoxicity against mammalian cells (L6 cell line). Deoxycyclovirobuxeine-B (12) (IC50 = 0.8 \u00b5mol\/L, SI = 108) and 29-trimethoxybenzoyloxy-obtusibuxoline (5) (IC50 = 0.5 \u00b5mol\/L, SI = 11) showed the highest activities with good selectivity indices against Tbr and Pf, respectively. Consequently, our findings provide valuable aminosteroid candidates that can serve as promising leads in our ongoing search for new drugs against HAT and Malaria.<\/jats:p>","DOI":"10.3390\/molecules30234558","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:56:34Z","timestamp":1764165394000},"page":"4558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antiprotozoal Aminosteroid Alkaloids from Buxus obtusifolia (Mildbr.) Hutch."],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9638-3250","authenticated-orcid":false,"given":"Justus Wambua","family":"Mukavi","sequence":"first","affiliation":[{"name":"University of M\u00fcnster, Institute of Pharmaceutical Biology and Phytochemistry (IPBP), PharmaCampus, Corrensstra\u00dfe 48, D-48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9959-9891","authenticated-orcid":false,"given":"Monica","family":"Cal","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute (Swiss TPH), Kreuzstrasse 2, CH-4123 Allschwil, Switzerland"},{"name":"University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1785-7302","authenticated-orcid":false,"given":"Marcel","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute (Swiss TPH), Kreuzstrasse 2, CH-4123 Allschwil, Switzerland"},{"name":"University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3122-1941","authenticated-orcid":false,"given":"Pascal","family":"M\u00e4ser","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute (Swiss TPH), Kreuzstrasse 2, CH-4123 Allschwil, Switzerland"},{"name":"University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5171-1940","authenticated-orcid":false,"given":"Njogu M.","family":"Kimani","sequence":"additional","affiliation":[{"name":"Department of Physical Sciences, University of Embu, Embu P.O. Box 6-60100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5821-8307","authenticated-orcid":false,"given":"Leonidah Kerubo","family":"Omosa","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science & Technology, University of Nairobi, Nairobi P.O. Box 30197-00100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2634-9705","authenticated-orcid":false,"given":"Thomas J.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"University of M\u00fcnster, Institute of Pharmaceutical Biology and Phytochemistry (IPBP), PharmaCampus, Corrensstra\u00dfe 48, D-48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kotepui, K.U., Masangkay, F.R., De Jesus Milanez, G., and Kotepui, M. (2021). Prevalence and Outcomes of Malaria as Co-Infection among Patients with Human African Trypanosomiasis: A Systematic Review and Meta-Analysis. Sci. 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