{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:21:44Z","timestamp":1785331304579,"version":"3.55.0"},"reference-count":85,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010679","name":"Pasteur Institute of Iran","doi-asserted-by":"publisher","award":["1802"],"award-info":[{"award-number":["1802"]}],"id":[{"id":"10.13039\/501100010679","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Toll-like receptor 7 (TLR7) plays a key role in the signaling pathways involved in immunity by recognizing pathogen-associated molecular patterns. Due to its broad effectiveness in various diseases and the limited number of drugs on the market that act on this receptor, it remains an ideal target for pharmaceutical scientists. To find novel TLR7 ligands, chemical feature-based pharmacophore models were prepared for TLR7 using Pharmit. This model was used for virtual screening in related databases, and the identified compounds were ranked using the Autodock docking method and minimum binding affinity. Among the identified compounds, the triazoloquinoxaline amine scaffold was selected as the lead structure, and its different derivatives were designed and docked again. Finally, two new series of [1,2,4]triazolo[4,3-a]quinoxalin-4-amine and 1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-amine derivatives were selected and synthesized using green chemistry routes. The cytotoxicity of the synthetic compounds was assessed using a macrophage cell line, and non-toxic compounds were then selected for evaluating cytokine stimulation. Ultimately, compound\n                    <jats:bold>7f<\/jats:bold>\n                    emerged as the most promising candidate for boosting the immune system based on fold change assessment compared to the control group. It exhibited the highest production of interleukin-1 (IL-1), tumor necrosis factor (TNF-\u03b1), and interferon beta (IFN-\u03b2) cytokines. Interestingly, the results of molecular docking aligned with the biological findings.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0336701","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T18:58:05Z","timestamp":1767034685000},"page":"e0336701","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of new triazoloquinoxaline amine derivatives with potent modulatory effects against Toll-like receptor 7 through pharmacophore-based virtual screening and molecular docking approaches"],"prefix":"10.1371","volume":"20","author":[{"given":"Nasrin Saberi","family":"Harooni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Naimi-Jamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-4258","authenticated-orcid":true,"given":"Sajjad","family":"Gharaghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asal","family":"Katebi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheila","family":"Ajdary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1221-4490","authenticated-orcid":true,"given":"Azar","family":"Tahghighi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"issue":"5","key":"pone.0336701.ref001","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors","volume":"11","author":"T Kawai","year":"2010","journal-title":"Nat Immunol"},{"key":"pone.0336701.ref002","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/164_2021_543","article-title":"Toll-Like Receptors in Adaptive Immunity","volume":"276","author":"V Kumar","year":"2022","journal-title":"Handb Exp Pharmacol"},{"key":"pone.0336701.ref003","first-page":"165","article-title":"Immune Response in Human Pathology: Infections Caused by Bacteria, Viruses, Fungi, and Parasites","author":"J Verhoef","year":"2019","journal-title":"Nijkamp and Parnham\u2019s Principles of Immunopharmacology. 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