{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:25:08Z","timestamp":1785799508515,"version":"3.56.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100011581","name":"Indian Institute of Technology Indore","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["NNP-BT\/PR40197\/BTIS\/137\/68\/2023"],"award-info":[{"award-number":["NNP-BT\/PR40197\/BTIS\/137\/68\/2023"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2025,1]]},"DOI":"10.1016\/j.ejphar.2024.177160","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T11:48:15Z","timestamp":1733140095000},"page":"177160","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Dorzolamide intermediates with potential anti-inflammatory activity"],"prefix":"10.1016","volume":"987","author":[{"given":"Rajat","family":"Atre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Obukhov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinmay Y.","family":"Majmudar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnaprasad","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fletcher A.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faaiza","family":"Siddiqi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed M.","family":"Faisal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek P.","family":"Varma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Imtaiyaz","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taj","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajanan N.","family":"Darwhekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8292-7130","authenticated-orcid":false,"given":"Mirza S.","family":"Baig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2024.177160_bib1","series-title":"From Innate Immunity to Immunological Memory, Current Topics in Microbiology and Immunology","first-page":"1","article-title":"TLR signaling","author":"Akira","year":"2006"},{"key":"10.1016\/j.ejphar.2024.177160_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.110176","article-title":"The indispensability of macrophage adaptor proteins in chronic inflammatory diseases","volume":"119","author":"Atre","year":"2023","journal-title":"Int. Immunopharm."},{"key":"10.1016\/j.ejphar.2024.177160_bib3","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.intimp.2017.04.028","article-title":"Heterotrimeric complex of p38 MAPK, PKC\u03b4, and TIRAP is required for AP1 mediated inflammatory response","volume":"48","author":"Baig","year":"2017","journal-title":"Int. Immunopharm."},{"key":"10.1016\/j.ejphar.2024.177160_bib4","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/JLB.MR0318-096R","article-title":"Understanding early TLR signaling through the Myddosome","volume":"105","author":"Balka","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.ejphar.2024.177160_bib46","series-title":"GROMACS 2022.2 Manual (2022.2). Zenodo","author":"Bauer","year":"2022"},{"key":"10.1016\/j.ejphar.2024.177160_bib5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-immunol-032414-112240","article-title":"Innate immune pattern recognition: a cell biological perspective","volume":"33","author":"Brubaker","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib6","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nri.2015.8","article-title":"Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease","volume":"16","author":"Cao","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib7","doi-asserted-by":"crossref","first-page":"10689","DOI":"10.1074\/jbc.274.16.10689","article-title":"Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction","volume":"274","author":"Chow","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2024.177160_bib8","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1164\/rccm.201508-1545CI","article-title":"Macrophages, inflammation, and lung cancer","volume":"193","author":"Conway","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.ejphar.2024.177160_bib9","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/35092578","article-title":"Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction","volume":"413","author":"Fitzgerald","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2024.177160_bib10","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejphar.2024.177160_bib11","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2174\/1568010054022024","article-title":"Macrophages in inflammation","volume":"4","author":"Fujiwara","year":"2005","journal-title":"CDTIA"},{"key":"10.1016\/j.ejphar.2024.177160_bib12","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/imm.12910","article-title":"Implications of macrophage polarization in autoimmunity","volume":"154","author":"Funes","year":"2018","journal-title":"Immunology"},{"key":"10.1016\/j.ejphar.2024.177160_bib13","doi-asserted-by":"crossref","first-page":"41974","DOI":"10.18632\/oncotarget.9633","article-title":"The inflammatory\/cancer-related IL-6\/STAT3\/NF-\u03baB positive feedback loop includes AUF1 and maintains the active state of breast myofibroblasts","volume":"7","author":"Hendrayani","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.ejphar.2024.177160_bib14","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/ct700301q","article-title":"Gromacs 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation","volume":"4","author":"Hess","year":"2008","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.ejphar.2024.177160_bib15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.imlet.2003.11.017","article-title":"Bruton's tyrosine kinase (Btk)\u2014the critical tyrosine kinase in LPS signalling?","volume":"92","author":"Jefferies","year":"2004","journal-title":"Immunol. Lett."},{"key":"10.1016\/j.ejphar.2024.177160_bib16","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like receptor signaling pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib17","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.tox.2006.04.053","article-title":"p38 mitogen-activated protein kinase up-regulates LPS-induced NF-\u03baB activation in the development of lung injury and RAW 264.7 macrophages","volume":"225","author":"Kim","year":"2006","journal-title":"Toxicology"},{"key":"10.1016\/j.ejphar.2024.177160_bib18","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1016\/j.molimm.2006.11.005","article-title":"Protein kinase C\u03b4 binds TIRAP\/Mal to participate in TLR signaling","volume":"44","author":"Kubo-Murai","year":"2007","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib19","series-title":"Macrophage Activation - Biology and Disease","article-title":"Macrophages: the potent immunoregulatory innate immune cells","author":"Kumar","year":"2020"},{"key":"10.1016\/j.ejphar.2024.177160_bib20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ejphar.2008.02.009","article-title":"p38MAPK inhibition attenuates LPS-induced acute lung injury involvement of NF-\u03baB pathway","volume":"584","author":"Liu","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2024.177160_bib21","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1134\/S0026893308040195","article-title":"Radius of gyration as an indicator of protein structure compactness","volume":"42","author":"Lobanov","year":"2008","journal-title":"Mol. Biol."},{"key":"10.1016\/j.ejphar.2024.177160_bib22","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1189\/jlb.0513307","article-title":"Bruton's tyrosine kinase\u2014an integral protein of B cell development that also has an essential role in the innate immune system","volume":"95","author":"L\u00f3pez-Herrera","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.ejphar.2024.177160_bib23","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"10.1016\/j.ejphar.2024.177160_bib24","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/35100529","article-title":"Toll-like receptors and innate immunity","volume":"1","author":"Medzhitov","year":"2001","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib25","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1056\/NEJMra1001976","article-title":"Immunodeficiency and genetic defects of pattern-recognition receptors","volume":"364","author":"Netea","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejphar.2024.177160_bib26","doi-asserted-by":"crossref","first-page":"a006049","DOI":"10.1101\/cshperspect.a006049","article-title":"Signaling in innate immunity and inflammation","volume":"4","author":"Newton","year":"2012","journal-title":"Cold Spring Harbor Perspect. Biol."},{"key":"10.1016\/j.ejphar.2024.177160_bib27","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/intimm\/dxy054","article-title":"Macrophages in inflammation, repair and regeneration","volume":"30","author":"Oishi","year":"2018","journal-title":"Int. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib28","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1128\/IAI.01412-06","article-title":"p38 mitogen-activated protein kinase controls NF-\u03baB transcriptional activation and tumor necrosis factor alpha production through RelA phosphorylation mediated by mitogen- and stress-activated protein kinase 1 in response to Borrelia burgdorferi antigens","volume":"75","author":"Olson","year":"2007","journal-title":"Infect. Immun."},{"key":"10.1016\/j.ejphar.2024.177160_bib29","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nri2079","article-title":"The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling","volume":"7","author":"O'Neill","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib30","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.compbiolchem.2014.04.001","article-title":"Structural evaluation of BTK and PKC\u03b4 mediated phosphorylation of MAL at positions Tyr86 and Tyr106","volume":"51","author":"Paracha","year":"2014","journal-title":"Comput. Biol. Chem."},{"key":"10.1016\/j.ejphar.2024.177160_bib31","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/mi.2017.68","article-title":"Protein kinase C-delta (PKC\u03b4), a marker of inflammation and tuberculosis disease progression in humans, is important for optimal macrophage killing effector functions and survival in mice","volume":"11","author":"Parihar","year":"2018","journal-title":"Mucosal Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib32","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1074\/jbc.M707400200","article-title":"Tyrosine phosphorylation of MyD88 adapter-like (mal) is critical for signal transduction and blocked in endotoxin tolerance","volume":"283","author":"Piao","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2024.177160_bib33","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejphar.2024.177160_bib34","doi-asserted-by":"crossref","first-page":"533","DOI":"10.4155\/fmc-2022-0260","article-title":"Dorzolamide suppresses PKC\u03b4 -TIRAP-p38 MAPK signaling axis to dampen the inflammatory response","volume":"15","author":"Rajpoot","year":"2023","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.ejphar.2024.177160_bib35","doi-asserted-by":"crossref","first-page":"5601","DOI":"10.1038\/s41598-022-09528-8","article-title":"TIRAP-mediated activation of p38 MAPK in inflammatory signaling","volume":"12","author":"Rajpoot","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2024.177160_bib36","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1080\/1062936X.2022.2035817","article-title":"Identification of novel inhibitors targeting TIRAP interactions with BTK and PKC\u03b4 in inflammation through an in silico approach","volume":"33","author":"Rajpoot","year":"2022","journal-title":"SAR QSAR Environ. Res."},{"key":"10.1016\/j.ejphar.2024.177160_bib37","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.697588","article-title":"TIRAP in the mechanism of inflammation","volume":"12","author":"Rajpoot","year":"2021","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib38","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1038\/s41598-017-02468-8","article-title":"PKC-\u03b4 isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-\u03baB and CXCL8 production","volume":"7","author":"Serrero","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2024.177160_bib39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/intimm\/dxh186","article-title":"Toll-like receptors in innate immunity","volume":"17","author":"Takeda","year":"2004","journal-title":"Int. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib40","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.ejphar.2024.177160_bib41","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: fast, flexible, and free","volume":"26","author":"Van Der Spoel","year":"2005","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejphar.2024.177160_bib42","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.3389\/fimmu.2019.01462","article-title":"The metabolic signature of macrophage responses","volume":"10","author":"Viola","year":"2019","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejphar.2024.177160_bib43","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","article-title":"Automatic atom type and bond type perception in molecular mechanical calculations","volume":"25","author":"Wang","year":"2006","journal-title":"J. Mol. Graph. Model."},{"key":"10.1016\/j.ejphar.2024.177160_bib44","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkab255","article-title":"ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties","volume":"49","author":"Xiong","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejphar.2024.177160_bib45","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1016\/j.bmc.2019.03.033","article-title":"Betulinic acid induces apoptosis and inhibits metastasis of human colorectal cancer cells in vitro and in vivo","volume":"27","author":"Zeng","year":"2019","journal-title":"Bioorg. Med. Chem."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299924008501?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299924008501?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T02:14:41Z","timestamp":1778638481000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299924008501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":46,"alternative-id":["S0014299924008501"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2024.177160","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dorzolamide intermediates with potential anti-inflammatory activity","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2024.177160","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"177160"}}