{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T09:13:47Z","timestamp":1760346827501,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T00:00:00Z","timestamp":1570492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Bio-guided fractionation performed on the leaves-derived ethanol extract of Esenbeckia alata (Rutaceae), a plant used in traditional medicine, led to the isolation of two alkaloids, kokusaginine 1 and flindersiamine 2, as main cytotoxic agents. Primary ethanolic extract and raw fractions exhibited cell inhibition against five cancer cell lines at different levels (25\u201397% inhibition at 50 \u00b5g\/mL) as well as isolated alkaloids 1\u20132 (30\u201390% inhibition at 20 \u00b5M). Although alkaloid 2 generally was the most active compound, both alkaloids showed a selective effect on K562, a human chronic myelogenous leukemia cell line. The E1-like ubiquitin-activating enzymes (e.g., UBA5) have been recently described as important targets for future treatment of cancer progression, such as leukemia, among others. Therefore, as a rationale to the observed cytotoxic selectivity, an in-silico evaluation by molecular docking and molecular dynamics was also explored. Compounds 1\u20132 exhibited good performance on the interaction within the active site of UBA5.<\/jats:p>","DOI":"10.3390\/biom9100585","type":"journal-article","created":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T09:00:38Z","timestamp":1570525238000},"page":"585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Bio-Guided Fractionation of Ethanol Extract of Leaves of Esenbeckia alata Kunt (Rutaceae) Led to the Isolation of Two Cytotoxic Quinoline Alkaloids: Evidence of Selectivity Against Leukemia Cells"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-226X","authenticated-orcid":false,"given":"Juan Manuel","family":"\u00c1lvarez-Caballero","sequence":"first","affiliation":[{"name":"Grupo de Qu\u00edmica y Bioprospecci\u00f3n de Productos Naturales, Universidad del Magdalena, Santa Marta 470004, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Enrique","family":"Cuca-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Productos Naturales Vegetales, Facultad de Ciencias, Departamento de Qu\u00edmica, Universidad Nacional de Colombia, Bogot\u00e1 D.C. 111321, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3553-9749","authenticated-orcid":false,"given":"Ericsson","family":"Coy-Barrera","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Facultad de Ciencias B\u00e1sicas y Aplicadas, Universidad Militar Nueva Granada, Cajic\u00e1 250247, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jep.2018.03.031","article-title":"Citri Reticulatae Pericarpium (Chenpi): Botany, ethnopharmacology, phytochemistry, and pharmacology of a frequently used traditional Chinese medicine","volume":"220","author":"Yu","year":"2018","journal-title":"J. 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