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Reverse docking identified the parasite-specific RNA-editing ligase 1 (REL1), completely absent in humans, as a high-confidence target (p-value = 1.76 \u00d7 10\n                      <jats:sup>-12<\/jats:sup>\n                      ; MaxTC = 0.31). Similarly, docking simulations revealed high binding probabilities for CaCS2 in two main cavities of REL1, named the orthosteric and alternative sites, in both parasites. Molecular dynamic simulations confirmed stable CaCS2 binding at the orthosteric site, while interactions at the alternative site were transient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Interestingly, CaCS2 was a specific ligand to REL1 and non cytotoxic to human cell lines, making it a promising scaffold for anti-trypanosomatid development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11686-026-01391-1","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:16:30Z","timestamp":1788761790000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Experimental and Computational Investigation of Azobenzenoid Derivatives Against Trypanosomatid: RNA Editing Ligase 1 as a Potential Molecular Target"],"prefix":"10.1007","volume":"71","author":[{"given":"Asif","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo Bento","family":"Balbinot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Lazarin-Bid\u00f3ia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maira Gabriela","family":"Paetzold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00cdris Nunes","family":"Seixas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Nunes","family":"Ramos Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Aparecida","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso Vataru","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio Augusto Vicente","family":"Seixas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"1391_CR1","doi-asserted-by":"crossref","unstructured":"The Kinetoplastid Infections (2021) Human African Trypanosomiasis (Sleeping Sickness), American Trypanosomiasis (Chagas Disease), and the Leishmaniases. 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