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In the present study, a series of 3\n                    <jats:italic>H<\/jats:italic>\n                    -1,2-dithiole-3-thione derivatives (\n                    <jats:bold>DTT-S1-18<\/jats:bold>\n                    ) were synthesized as promising anticancer agents, and the structures of products were confirmed by spectral techniques. H\n                    <jats:sub>2<\/jats:sub>\n                    S-releasing experiments showed that most of the compounds released higher amounts of H\n                    <jats:sub>2<\/jats:sub>\n                    S slowly over time compared to standard\n                    <jats:bold>ADT-OH<\/jats:bold>\n                    . All compounds were tested for antiproliferative activity on HT-29, PC-3, MCF-7, and HUVEC cell lines. Compounds\n                    <jats:bold>DTT-S6<\/jats:bold>\n                    (3-nitrophenyl derivative) and\n                    <jats:bold>DTT-S8<\/jats:bold>\n                    (methionine derivative) have the lowest IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 41.6 and 38.9 \u00b5M on the MCF-7 cell line, respectively. Based on the wound healing and colony formation assays performed in MCF-7 cells, the wound areas were not significantly changed after treatment with compounds\n                    <jats:bold>DTT-S6<\/jats:bold>\n                    and\n                    <jats:bold>DTT-S8<\/jats:bold>\n                    , whereas compound\n                    <jats:bold>DTT-S8<\/jats:bold>\n                    at double IC\n                    <jats:sub>50<\/jats:sub>\n                    dose inhibited colony formation by 81.82%. In addition, molecular docking, MD simulations, MM\/GBSA binding free energy calculations, and binary QSAR analyses were performed to explore the potential target interactions and predicted activity profiles of the synthesized compounds toward inflammation-related proteins, including COX-1, COX-2, 5-LOX, and iNOS, thereby supporting the development of mechanistic hypotheses for future validation. Furthermore, structure\u2013activity relationship (SAR) analyses were conducted to correlate the structural characteristics of the synthesized compounds with their H\n                    <jats:sub>2<\/jats:sub>\n                    S releasing potential and biological profiles. Overall, this work integrates experimental anticancer evaluation with computational pathway and structure-based cancer\/inflammation analyses to characterize novel DTT-based H\n                    <jats:sub>2<\/jats:sub>\n                    S donors. The findings identify particularly compound\n                    <jats:bold>DTT-S8<\/jats:bold>\n                    , as a promising in vitro anticancer candidate, while the computational results suggest a putative involvement of inflammation-related targets, particularly the COX-2\/5-LOX axis, which requires direct biochemical and cellular validation.\n                  <\/jats:p>","DOI":"10.1007\/s11030-026-11635-x","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T07:50:05Z","timestamp":1785052205000},"page":"10387-10416","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New 3H-1,2-Dithiole-3-thione derivatives: Design and synthesis, H2S-release profile, in vitro anticancer activity, and in silico multi-target assessment"],"prefix":"10.1007","volume":"30","author":[{"given":"Semra","family":"Altunsoy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakup Berkay","family":"Y\u0131lmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u011fba","family":"G\u00fcng\u00f6r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazal Nazl\u0131can","family":"Atalay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mine","family":"Isao\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar","family":"Durda\u011f\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Ay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tugba","family":"Boyunegmez Tumer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"issue":"11","key":"11635_CR1","doi-asserted-by":"publisher","first-page":"3338","DOI":"10.3390\/cancers12113338","volume":"12","author":"P Faris","year":"2020","unstructured":"Faris P, Ferulli F, Vismara M, Tanzi M, Negri S, Rumolo A, Lefkimmiatis K, Maestri M, Shekha M, Pedrazzoli P, Guidetti GF, Montagna D, Moccia F (2020) Hydrogen sulfide-evoked intracellular Ca2+ signals in primary cultures of metastatic colorectal cancer cells. 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