{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:24:57Z","timestamp":1777386297607,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Aplysinopsins are a class of marine indole alkaloids that exhibit a wide range of biological activities. Although both the indole and N-benzyl moieties of aplysinopsins are known to possess antiproliferative activity against cancer cells, their mechanism of action remains unclear. Through in vitro and in vivo proliferation and viability screening of newly synthesized aplysinopsin analogs on myelogenous leukemia cell lines and zebrafish toxicity tests, as well as analysis of differential toxicity in noncancerous RPMI 1788 cells and PBMCs, we identified EE-84 as a promising novel drug candidate against chronic myeloid leukemia. This indole derivative demonstrated drug-likeness in agreement with Lipinski\u2019s rule of five. Furthermore, EE-84 induced a senescent-like phenotype in K562 cells in line with its cytostatic effect. EE-84-treated K562 cells underwent morphological changes in line with mitochondrial dysfunction concomitant with autophagy and ER stress induction. Finally, we demonstrated the synergistic cytotoxic effect of EE-84 with a BH3 mimetic, the Mcl-1 inhibitor A-1210477, against imatinib-sensitive and resistant K562 cells, highlighting the inhibition of antiapoptotic Bcl-2 proteins as a promising novel senolytic approach against chronic myeloid leukemia.<\/jats:p>","DOI":"10.3390\/md19060285","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:15:15Z","timestamp":1621602915000},"page":"285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Anti-Leukemic Properties of Aplysinopsin Derivative EE-84 Alone and Combined to BH3 Mimetic A-1210477"],"prefix":"10.3390","volume":"19","author":[{"given":"Sungmi","family":"Song","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08626, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sua","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08626, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7505-3356","authenticated-orcid":false,"given":"Eslam R.","family":"El-Sawy","sequence":"additional","affiliation":[{"name":"Chemistry Department of Natural Compounds, National Research Centre, Dokki, 12622 Giza, Egypt"},{"name":"UMR CNRS 7565 SRSMC, Universit\u00e9 du Lorraine, 57070 Metz, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-8176","authenticated-orcid":false,"given":"Claudia","family":"Cerella","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08626, Korea"},{"name":"Laboratoire de Biologie Mol\u00e9culaire et Cellulaire du Cancer, H\u00f4pital Kirchberg, 9, Rue Edward Steichen, 2540 Luxembourg, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Orlikova-Boyer","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08626, Korea"},{"name":"Laboratoire de Biologie Mol\u00e9culaire et Cellulaire du Cancer, H\u00f4pital Kirchberg, 9, Rue Edward Steichen, 2540 Luxembourg, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-1755","authenticated-orcid":false,"given":"Gilbert","family":"Kirsch","sequence":"additional","affiliation":[{"name":"UMR CNRS 7565 SRSMC, Universit\u00e9 du Lorraine, 57070 Metz, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christo","family":"Christov","sequence":"additional","affiliation":[{"name":"Service d\u2019Histologie, Facult\u00e9 de M\u00e9dicine, Universit\u00e9 de Lorraine, INSERM U1256 NGERE, 54000 Nancy, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Dicato","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie Mol\u00e9culaire et Cellulaire du Cancer, H\u00f4pital Kirchberg, 9, Rue Edward Steichen, 2540 Luxembourg, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Diederich","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08626, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40880-016-0108-0","article-title":"The Philadelphia chromosome in leukemogenesis","volume":"35","author":"Kang","year":"2016","journal-title":"Chin. 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