{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:23:03Z","timestamp":1791951783152,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The unique physicochemical and structural flexibility of ionic liquids (ILs) allows for fine modulation of biological activity, thus offering potential as the next\u2010generation anticancer lead compounds with improved selectivity and efficacy. In this study, a new series of benzyl functionalised imidazolium ILs with varying\n                    <jats:italic>para<\/jats:italic>\n                    substituents (R = H, CH\n                    <jats:sub>3<\/jats:sub>\n                    , F, Cl, Br, NO\n                    <jats:sub>2<\/jats:sub>\n                    , CN) is reported. Their cytotoxicity against human neuroblastoma (SHSY\u20105Y), estrogen\u2010positive breast cancer cells (MCF\u20107), neuroblastoma (SHSY\u20105Y), lung carcinoma (A549), liver cancer cells (HepG2), colorectal adenocarcinoma (HT\u201029), and mouse embryonic fibroblasts (NIH 3T3) was evaluated. The ILs were cytotoxic against all tested cell lines but were generally more selective toward MCF\u20107. ILs bearing H, CH\n                    <jats:sub>3<\/jats:sub>\n                    , F, Cl, and Br exhibited similar growth inhibition strength against MCF\u20107 (IC\n                    <jats:sub>50<\/jats:sub>\n                    ranged between 3.99 and 5.20\u2009\u00b5M) that was superior to that of tamoxifen (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200915.41\u2009\u00b5M). However, the presence of NO\n                    <jats:sub>2<\/jats:sub>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20098.10\u2009\u00b5M) and CN (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200917.52\u2009\u00b5M) significantly reduced their growth inhibition potentials (two\u2010 to four\u2010fold) in NIH 3T3 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&gt;\u200940\u2009\u00b5M). The NO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010containing IL had a broad safety window against MCF\u20107 (selectivity index &gt;\u20094). All the ILs have high drug\u2010likeness (complied with all criteria stated in Lipinski's rule of five and Veber's rule). The most selective IL against MCF\u20107 (R = NO\n                    <jats:sub>2<\/jats:sub>\n                    ) induced caspase\u2010dependent but reactive oxygen species independent pro\u2010apoptosis in MCF\u20107 cells. Substituent modifications in the benzyl group regulated cytotoxicity and selectivity, thus reinforcing ILs as a valuable platform for the development of a new class of effective anticancer lead compounds.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70194","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T18:21:30Z","timestamp":1764008490000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Benzyl\u2010Functionalised Imidazolium Ionic Liquids as Lead Candidates Against Human Breast Cancer: An Integrated In Vitro and In Silico Screening Approach"],"prefix":"10.1002","volume":"86","author":[{"given":"Boon\u2010Keat","family":"Khor","sequence":"first","affiliation":[{"name":"Centre for Drug Research Universiti Sains Malaysia Pulau Pinang Gelugor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia En","family":"Lau","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences Universiti Sains Malaysia Pulau Pinang Gelugor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatini Syazana Sharul","family":"Azman","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences Universiti Sains Malaysia Pulau Pinang Gelugor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng Poh","family":"Ng","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences Universiti Sains Malaysia Pulau Pinang Gelugor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikneswaran","family":"Murugaiyah","sequence":"additional","affiliation":[{"name":"Centre for Drug Research Universiti Sains Malaysia Pulau Pinang Gelugor Malaysia"},{"name":"School of Pharmaceutical Sciences Universiti Sains Malaysia Pulau Pinang Gelugor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5050-8230","authenticated-orcid":false,"given":"Nelson Jeng\u2010Yeou","family":"Chear","sequence":"additional","affiliation":[{"name":"Centre for Drug Research Universiti Sains Malaysia Pulau Pinang Gelugor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9637-7563","authenticated-orcid":false,"given":"WanSinn","family":"Yam","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences Universiti Sains Malaysia Pulau Pinang Gelugor 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