{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:51:20Z","timestamp":1791539480779,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Inflammation is a tightly regulated response that maintains tissue homeostasis; however, its dysregulation in the lung contributes to acute lung injury (ALI), characterised by excessive cytokine production, oxidative stress, epithelial\u2010endothelial barrier disruption, and impaired gas exchange. In the current study, we report the synthesis of 1,2,3,4\u2010tetrahydro\u2010\u03b2\u2010carboline (TH\u03b2C)\u2010based spirocyclic peptides by an efficient cascade strategy involving\n                    <jats:italic>N<\/jats:italic>\n                    \u2010Boc deprotection and Pictet\u2010Spengler cyclization, which was developed for tryptophan\u2010containing peptides using 9\u2010fluorenone, enabling the synthesis of TH\u03b2C peptides. The reaction proceeds under mild conditions [C\n                    <jats:sub>6<\/jats:sub>\n                    F\n                    <jats:sub>5<\/jats:sub>\n                    OH (pentafluorophenol) catalyst, HFIP (1,1,1,3,3,3\u2010Hexafluoro\u20102\u2010propanol) solvent] to generate a novel spiro\u2010\u03b2\u2010carboline scaffold, with broad substrate scope across aromatic, aliphatic, and alicyclic ketones. Further, the anti\u2010inflammatory potential of TH\u03b2C derivatives was evaluated in LPS\u2010stimulated macrophages and lung epithelial cells. Initial screening demonstrated that compounds\n                    <jats:bold>3a, 3aa, 3c<\/jats:bold>\n                    ,\n                    <jats:bold>3e<\/jats:bold>\n                    , and\n                    <jats:bold>3\u2009g<\/jats:bold>\n                    (20\u2009\u03bcM) significantly reduced\n                    <jats:italic>Il\u20101\u03b2<\/jats:italic>\n                    levels compared with the LPS control. Subsequent structure\u2013activity relationship studies identified compounds\n                    <jats:bold>3aa<\/jats:bold>\n                    and\n                    <jats:bold>3ag<\/jats:bold>\n                    as potent inhibitors of\n                    <jats:italic>Il\u20101\u03b2<\/jats:italic>\n                    expression, while compounds\n                    <jats:bold>3aa, 3ad, 3af<\/jats:bold>\n                    and\n                    <jats:bold>3ag<\/jats:bold>\n                    effectively suppressed\n                    <jats:italic>Ccl\u20102<\/jats:italic>\n                    and\n                    <jats:italic>Cox\u20102<\/jats:italic>\n                    expression. Based on their ability to attenuate intracellular ROS levels, compounds\n                    <jats:bold>3aa<\/jats:bold>\n                    and\n                    <jats:bold>3ag<\/jats:bold>\n                    were selected for further dose\u2010response evaluation and assessment in lung epithelial cells. These compounds significantly downregulated key inflammatory mediators in both macrophages and epithelial cells. Immunocytochemical analyses further revealed that compounds\n                    <jats:bold>3aa<\/jats:bold>\n                    and\n                    <jats:bold>3ag<\/jats:bold>\n                    reduced LPS\u2010induced VCAM expression and restored caveolin levels, indicating improved barrier integrity. Collectively, compounds\n                    <jats:bold>3aa<\/jats:bold>\n                    and\n                    <jats:bold>3ag<\/jats:bold>\n                    attenuate LPS\u2010induced inflammation and oxidative stress while preserving epithelial barrier integrity, supporting their potential as leads for pulmonary inflammatory disorders.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70384","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:52:30Z","timestamp":1789563150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis of Tetrahydro\u2010\u03b2\u2010Carboline\u2010Based Spirocyclic Peptides via Cascade\n                    <i>N<\/i>\n                    \u2010Boc Deprotection and Pictet\u2010Spengler Reaction of Tryptophan: Potent Anti\u2010Inflammatory and Anti\u2010Oxidant Activities"],"prefix":"10.1002","volume":"87","author":[{"given":"Shravani","family":"Battula","sequence":"first","affiliation":[{"name":"Department of Organic Synthesis and Process Chemistry CSIR\u2010Indian Institute of Chemical Technology Hyderabad Telangana India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishnavi","family":"Kambhampati","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad Uttar Pradesh India"},{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Balaji","family":"Andugulapati","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad Uttar Pradesh India"},{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiranmai","family":"Nayani","sequence":"additional","affiliation":[{"name":"Department of Organic Synthesis and Process Chemistry CSIR\u2010Indian Institute of Chemical Technology Hyderabad Telangana India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113321"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00393a023"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9422(90)80080-Z"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011306517653"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm960062t"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12030548"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.08.022"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.5570310231"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr050521a"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.03.030"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/00397910802238718"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.12.3.264"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00090a045"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2014.04.077"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756287214531639"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)90342-4"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf030324h"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.07.047"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600610602"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.51.1368"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.07.002"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3CC06115A"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030080s"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201202745"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/asia.202401244"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2004.10.025"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2ob26301g"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja990184l"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2025.02.003"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06994-2"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-018-1251-5"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02127-9"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.22193"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202203924"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2019.01.004"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol034526a"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.0c01485"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo049918p"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(80)90538-5"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00513.2005"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cber.19110440309"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05134-8"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.22070"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)95036-6"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-016-0560-6"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193225"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2006.12.112"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2007.02.123"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-1998-1604"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112888"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-005-4386-8"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1039\/b212063a"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201008071"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2005.06.027"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153729"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2003.11.108"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol802173r"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA03628J"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00813-2"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70616"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1037850"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1551138"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2026.01.013"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100410f"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1321095"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2025.2452082"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70384","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ddr.70384","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:18:07Z","timestamp":1791537487000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":66,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/ddr.70384"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70384","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"assertion":[{"value":"2026-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70384"}}