{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:04:34Z","timestamp":1788815074443,"version":"build-2803163510"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education (MOHE) Malaysia, through FUNDAMENTAL RESEARCH GRANT SCHEME","award":["FRGS\/1\/2020\/STG02\/UKM\/03\/1"],"award-info":[{"award-number":["FRGS\/1\/2020\/STG02\/UKM\/03\/1"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Acute lymphoblastic leukemia (ALL) is a common cancer affecting children worldwide, and current treatment has adverse effects such as neurotoxicity. To overcome this problem, new organotin (IV) dithiocarbamate compounds were synthesized. In this study, the T-lymphoblastic leukemia cell line (CCL-119) was tested against seven new compounds: diphenyltin (IV) diisopropyl dithiocarbamate (ODTC 1), diphenyltin (IV) diallyl dithiocarbamate (ODTC 2), triphenyltin (IV) diisopropyl dithiocarbamate (ODTC 3), triphenyltin (IV) diallyl dithiocarbamate (ODTC 4), triphenyltin (IV) diethyl dithiocarbamate (ODTC 5), dimethyltin (IV) diisopropyl dithiocarbamate (ODTC 6) and dimethyltin (IV) diethyl dithiocarbamate (ODTC 7) hereafter referred to as ODTC 1\u20137, to identify their cytotoxic effects (MTT assay), mode of cell death (Annexin V FITC\/PI staining) and effects on the cell cycle (RNase\/PI staining) as well as genotoxic effects (alkaline comet assay). Results obtained after 24 hours of exposure showed that all organotin (IV) dithiocarbamate compounds (ODTC 1\u20137) exhibited potent cytotoxicity, with median inhibitory concentration (IC<jats:sub>50<\/jats:sub>) values ranging from 0.18 \u00b5M to 3.10 \u00b5M. The selectivity index showed that diphenyltin (IV) and triphenyltin (IV) dithiocarbamate compounds are more selective towards CCL-119 cells. All ODTC compounds induced apoptosis in CCL-119 cells, and each compound caused cell cycle arrest at specific phases, indicating diverse mechanisms of action. Apoptosis and cell cycle arrest were confirmed by flow cytometry. Treatment of the compounds caused significant (p\u2009&lt;\u20090.05) DNA damage compared to the negative control, with ODTC 1 causing the highest genotoxic effects. In conclusion, diphenyltin (IV) and triphenyltin (IV) dithiocarbamate compounds show good potential as anti-leukemia agents. However, further studies on the mechanisms of action need to be conducted to have better insights into the effect of this compound on CCL-119 leukemia cells.<\/jats:p>","DOI":"10.1371\/journal.pone.0329860","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T17:37:43Z","timestamp":1754933863000},"page":"e0329860","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of organotin (IV) dithiocarbamate compounds as potential anti-leukemia agents towards CCRF-CEM (CCL-119) cell line: Cytotoxic, apoptotic, cell cycle and genotoxic study"],"prefix":"10.1371","volume":"20","author":[{"given":"Nabiha Hidayah","family":"Abdul Razak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Rasyiqin","family":"Rasli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norsyahira","family":"Mohamad Zamri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9657-9453","authenticated-orcid":true,"given":"Asmah","family":"Hamid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Normah","family":"Awang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurul Farahana","family":"Kamaludin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"pone.0329860.ref001","unstructured":"Malaysia, MOH. Malaysia National Cancer Registry Report 2012\u20136. 2019."},{"issue":"5","key":"pone.0329860.ref002","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.31557\/APJCP.2020.21.5.1487","article-title":"GLOBAL Leukemia in Children 0-14 Statistics 2018, Incidence and Mortality and Human Development Index (HDI): GLOBOCAN Sources and Methods","volume":"21","author":"SM Namayandeh","year":"2020","journal-title":"Asian Pac J Cancer Prev"},{"key":"pone.0329860.ref003","unstructured":"American Cancer Society. Cancer Facts & Figures 2022 [PDF]. 2022. Available from: https:\/\/www.cancer.org\/content\/dam\/cancer-org\/research\/cancer-facts-and-statistics\/annual-cancer-facts-and-figures\/2022\/2022-cancer-facts-and-figures.pdf"},{"issue":"6","key":"pone.0329860.ref004","doi-asserted-by":"crossref","DOI":"10.1038\/bcj.2017.53","article-title":"Acute lymphoblastic leukemia: a comprehensive review and 2017 update","volume":"7","author":"T Terwilliger","year":"2017","journal-title":"Blood Cancer J"},{"key":"pone.0329860.ref005","first-page":"7","article-title":"Cancer Statistics, 2022","volume":"72","author":"RL Siegel","year":"2022","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"10","key":"pone.0329860.ref006","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.3390\/molecules23102571","article-title":"Organotin(IV) Dithiocarbamate Complexes: Chemistry and Biological Activity","volume":"23","author":"JO Adeyemi","year":"2018","journal-title":"Molecules"},{"key":"pone.0329860.ref007","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.13005\/ojc\/330420","article-title":"Cytotoxicity assessment of organotin (IV)(2-metoxyethyl) methyldithiocarbamate compounds in human leukemia cell lines","volume":"33","author":"NF Kamaludin","year":"2017","journal-title":"Oriental Journal of Chemistry"},{"key":"pone.0329860.ref008","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.jorganchem.2005.12.025","article-title":"Biological activity studies on organotin (IV) n complexes and parent compounds","volume":"691","author":"C Pellerito","year":"2006","journal-title":"Journal of Organometallic Chemistry"},{"issue":"5","key":"pone.0329860.ref009","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1016\/j.sjbs.2021.02.060","article-title":"Synthesis and cytotoxic activity of organotin(IV) diallyldithiocarbamate compounds as anticancer agent towards colon adenocarcinoma cells (HT-29)","volume":"28","author":"FN Haezam","year":"2021","journal-title":"Saudi J Biol Sci"},{"key":"pone.0329860.ref010","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1107\/S2056989019012490","article-title":"(N,N-Diiso-propyl-dithio-carbamato)tri-phenyl-tin(IV): crystal structure, Hirshfeld surface analysis and computational study","volume":"75","author":"FN Haezam","year":"2019","journal-title":"Acta Crystallogr E Crystallogr Commun"},{"key":"pone.0329860.ref011","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1107\/S2056989020000122","article-title":"(N,N-Di-allyl-dithio-carbamato-\u03ba2S,S\u2019)tri-phenyltin(IV) and bis-(N,N-di-allyl-dithio-carbamato-\u03ba2S,S\u2019)di-phenyl-tin(IV): crystal structure, Hirshfeld surface analysis and computational study","volume":"76","author":"FN Haezam","year":"2020","journal-title":"Acta Crystallogr E Crystallogr Commun"},{"key":"pone.0329860.ref012","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1515\/ncrs-2019-0894","article-title":"Crystal structure of dimethylbis (diisopropyldithiocarbamato-\u03ba2S, S\u2032) tin (IV), C16H34N2S4Sn","volume":"235","author":"FN Haezam","year":"2020","journal-title":"Zeitschrift f\u00fcr Kristallographie-New Crystal Structures"},{"key":"pone.0329860.ref013","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3844\/ajassp.2011.310.317","article-title":"Synthesis, characterization and biological activities of organotin (IV) methylcyclohexyldithiocarbamate compounds","volume":"8","author":"N Awang","year":"2011","journal-title":"American Journal of Applied Sciences"},{"key":"pone.0329860.ref014","doi-asserted-by":"crossref","unstructured":"Abd Aziz NA, Awang N, Chan KM, Kamaludin NF, Anuar NNM. Organotin (IV) Dithiocarbamate Compounds as an Anticancer Agent: A Review of Synthesis and Cytotoxicity Study. 2023.","DOI":"10.20944\/preprints202305.1910.v1"},{"key":"pone.0329860.ref015","unstructured":"Chromatography, G. Chemistry LibreTexts. Home\u2013Chemistry LibreTexts [online]. 2020. Copyright\u00a9 Copyright."},{"issue":"8","key":"pone.0329860.ref016","doi-asserted-by":"crossref","first-page":"9502","DOI":"10.3390\/ijms13089502","article-title":"Thermal studies of Zn(II), Cd(II) and Hg(II) complexes of some N-alkyl-N-phenyl-dithiocarbamates","volume":"13","author":"DC Onwudiwe","year":"2012","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0329860.ref017","first-page":"1920","article-title":"Synthesis and Characterisation of New Organotin (IV)(2-Methoxyethyl)-methyldithiocarbamate Complexes","volume":"7","author":"R Mohamad","year":"2016","journal-title":"Research Journal of Pharmaceutical Biological and Chemical Sciences"},{"issue":"8","key":"pone.0329860.ref018","first-page":"2993","article-title":"Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells","volume":"29","author":"RB Badisa","year":"2009","journal-title":"Anticancer Res"},{"issue":"4","key":"pone.0329860.ref019","doi-asserted-by":"crossref","first-page":"859","DOI":"10.3390\/molecules25040859","article-title":"Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms","volume":"25","author":"A Attanzio","year":"2020","journal-title":"Molecules"},{"issue":"8","key":"pone.0329860.ref020","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.3390\/molecules25081789","article-title":"Synthesis, Antiproliferative Activity and Molecular Docking Studies of Novel Doubly Modified Colchicine Amides and Sulfonamides as Anticancer Agents","volume":"25","author":"J Krzywik","year":"2020","journal-title":"Molecules"},{"key":"pone.0329860.ref021","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jep.2005.03.011","article-title":"Evaluation of plants used for antimalarial treatment by the Maasai of Kenya","volume":"101","author":"A Koch","year":"2005","journal-title":"J Ethnopharmacol"},{"issue":"4","key":"pone.0329860.ref022","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: a review of programmed cell death","volume":"35","author":"S Elmore","year":"2007","journal-title":"Toxicol Pathol"},{"issue":"4","key":"pone.0329860.ref023","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S1534-5807(03)00090-X","article-title":"Annexin I Is an Endogenous Ligand That Mediates Apoptotic Cell Engulfment","volume":"4","author":"S Arur","year":"2003","journal-title":"Developmental Cell"},{"issue":"8","key":"pone.0329860.ref024","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.3390\/molecules28083376","article-title":"Series of Organotin(IV) Compounds with Different Dithiocarbamate Ligands Induced Cytotoxicity, Apoptosis and Cell Cycle Arrest on Jurkat E6.1, T Acute Lymphoblastic Leukemia Cells","volume":"28","author":"NR Rasli","year":"2023","journal-title":"Molecules"},{"key":"pone.0329860.ref025","doi-asserted-by":"crossref","DOI":"10.1080\/00958972.2015.1046849","article-title":"Synthesis, characterization, biological activities, crystal structure and DNA binding of organotin(IV) 5-chlorosalicylates","volume":"68","author":"S Hussain","year":"2015","journal-title":"Journal of Coordination Chemistry"},{"issue":"2","key":"pone.0329860.ref026","first-page":"1457","article-title":"Toxicity mechanism of triphenyltin (IV) butylphenyldithiocarbamate on acute lymphoblastic cells, Jurkat E6. 1","volume":"6","author":"N Awang","year":"2015","journal-title":"Research Journal of Pharmaceutical Biological and Chemical Sciences"},{"key":"pone.0329860.ref027","doi-asserted-by":"crossref","first-page":"657599","DOI":"10.3389\/fchem.2021.657599","article-title":"Cellular Basis of Organotin(IV) Derivatives as Anticancer Metallodrugs: A Review","volume":"9","author":"SN Syed Annuar","year":"2021","journal-title":"Front Chem"},{"key":"pone.0329860.ref028","first-page":"63","article-title":"DNA damaging effect of selected salted and fermented food products against Chang liver cell","volume":"5","author":"R Sharif","year":"2007","journal-title":"Journal Sains Kesihatan Malaysia"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0329860","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T17:37:49Z","timestamp":1754933869000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0329860"}},"subtitle":[],"editor":[{"given":"Abdelwahab","family":"Omri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":28,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0329860","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,11]]}}}