{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:55:15Z","timestamp":1784116515052,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T00:00:00Z","timestamp":1607126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Leukemia is a blood or bone marrow cancer with increasing incidence in developed regions of the world. Currently, there is an ongoing need for novel and safe anti-leukemic agents, as no fully effective chemotherapy is available to treat this life-threatening disease. Herein, are reported the isolation, structural elucidation, and anti-leukemic evaluation of twenty-nine withanolide-type steroids (1\u201329) from Withania aristata. Among them, the new isolated withanolides, withaperoxidins A\u2013D (1\u20134) have an unusual six-membered cyclic peroxide moiety on the withasteroid skeleton as a structural novelty. Their structures have been elucidated by means of spectroscopic analyses, including 2D NMR experiments. In addition, extensive structure\u2013activity relationships and in silico ADME studies were employed to understand the pharmacophore and pharmacokinetic properties of this series of withasteroids. Compounds 15, 16, and 22 together with withaferin A (14) were identified as having improved antiproliferative effect (IC50 ranging from 0.2 to 0.7 \u03bcM) on human leukemia HL-60 cell lines compared with the reference drug, etoposide. This cytotoxic potency was also coupled with good selectivity index (SI 33.0\u20139.2) on non-tumoral Vero cell line and in silico drug likeness. These findings revealed that these natural withasteroids are potential candidates as chemotherapeutic agents in the treatment of leukemia.<\/jats:p>","DOI":"10.3390\/molecules25235744","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T22:15:36Z","timestamp":1607638536000},"page":"5744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Withanolide-Type Steroids from Withania aristata as Potential Anti-Leukemic Agents"],"prefix":"10.3390","volume":"25","author":[{"given":"Laila M.","family":"Moujir","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology, Cell Biology and Genetic, Faculty of Pharmacy, Universidad de La Laguna, Avenida Astrofisico Francisco S\u00e1nchez s\/n, 38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel G.","family":"Llanos","sequence":"additional","affiliation":[{"name":"Institute of Bio-Org\u00e1nica Antonio Gonz\u00e1lez and Organic Chemistry Department, Universidad de La Laguna, Avenida Astrof\u00edsico Francisco S\u00e1nchez 2, 38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Araujo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology, Cell Biology and Genetic, Faculty of Pharmacy, Universidad de La Laguna, Avenida Astrofisico Francisco S\u00e1nchez s\/n, 38206 La Laguna, Spain"},{"name":"Clinical Laboratory Career, Faculty of Health Sciences, Universidad Nacional de Chimborazo, Avenida Antonio Jos\u00e9 de Sucre, Riobamba 060150, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Amesty","sequence":"additional","affiliation":[{"name":"Institute of Bio-Org\u00e1nica Antonio Gonz\u00e1lez and Organic Chemistry Department, Universidad de La Laguna, Avenida Astrof\u00edsico Francisco S\u00e1nchez 2, 38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7698-2704","authenticated-orcid":false,"given":"Isabel L.","family":"Bazzocchi","sequence":"additional","affiliation":[{"name":"Institute of Bio-Org\u00e1nica Antonio Gonz\u00e1lez and Organic Chemistry Department, Universidad de La Laguna, Avenida Astrof\u00edsico Francisco S\u00e1nchez 2, 38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-607X","authenticated-orcid":false,"given":"Ignacio A.","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Institute of Bio-Org\u00e1nica Antonio Gonz\u00e1lez and Organic Chemistry Department, Universidad de La Laguna, Avenida Astrof\u00edsico Francisco S\u00e1nchez 2, 38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a34819","DOI":"10.1101\/cshperspect.a034819","article-title":"Epidemiology and etiology of leukemia and lymphoma","volume":"10","author":"Bispo","year":"2020","journal-title":"Cold Spring Harb. 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