{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:22:28Z","timestamp":1784175748526,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jiangsu Higher Education Institution Innovative Research Team For Science and Technology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Human intestinal bacteria are the primary producers of azo reductase, and the content of azo reductase is closely associated with various intestinal diseases, including ulcerative colitis (UC). The rapid detection of changes in azo reductase levels is crucial for diagnosing and promptly intervening in UC. In this study, a therapeutic agent, FAI, specifically targeting UC, was designed and synthesized. This agent was developed by linking the anti-inflammatory drug indomethacin to flavonols with antioxidant activity via an azo bond (off\u2013on). Breakage of the azo bond breaks results in the release of both fluorophores and drugs, achieving targeted tracing and integrated treatment effects. In vivo and in vitro fluorescence imaging experiments were used to demonstrate the potential of FAI in the diagnosis of UC, together with synergistic therapeutic effects through the release of both fluorophores and anti-inflammatory agents. Therefore, this diagnostic agent shows promise as a potential tool for diagnosing and treating UC.<\/jats:p>","DOI":"10.3390\/molecules29174244","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T11:53:11Z","timestamp":1725623591000},"page":"4244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design and Synthesis of an Azo Reductase Responsive Flavonol\u2013Indomethacin Hybrid Used for the Diagnosis and Treatment of Colitis"],"prefix":"10.3390","volume":"29","author":[{"given":"Yaqin","family":"Gu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng 224005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng 224005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jine","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng 224005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenna","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng 224005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng 224005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng 224005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1053\/j.sempedsurg.2017.10.003","article-title":"Clinical presentation of Crohn\u2019s, ulcerative colitis, and indeterminate colitis: Symptoms, extraintestinal manifestations, and disease phenotypes","volume":"26","author":"Yu","year":"2017","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/S0140-6736(12)60150-0","article-title":"Ulcerative colitis","volume":"380","author":"Eckmann","year":"2012","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7016468","DOI":"10.1155\/2017\/7016468","article-title":"Huangqin-Tang and Ingredients in Modulating the Pathogenesis of Ulcerative Colitis","volume":"2017","author":"Wang","year":"2017","journal-title":"Evid. Based Compl. Alt."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0955-2863(02)00208-5","article-title":"Flavonoid antioxidants: Chemistry, metabolism and structure-activity relationships","volume":"13","author":"Heim","year":"2002","journal-title":"J. Nutr. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1111\/bph.13571","article-title":"Azoreductases in drug metabolism","volume":"174","author":"Ryan","year":"2017","journal-title":"Brit. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10901","DOI":"10.1021\/acs.analchem.9b02857","article-title":"In-Situ Imaging of Azoreductase Activity in the Acute and Chronic Ulcerative Colitis Mice by a Near-Infrared Fluorescent Probe","volume":"91","author":"Tian","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6854","DOI":"10.1021\/acs.analchem.7b01351","article-title":"Facile and Sensitive Near-Infrared Fluorescence Probe for the Detection of Endogenous Alkaline Phosphatase Activity In Vivo","volume":"89","author":"Li","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1021\/acs.analchem.8b04416","article-title":"Fluorescence-Guided Cancer Diagnosis and Surgery by a Zero Cross Talk Ratiometric Near-Infrared \u03b3-Glutamyltranspeptidase Fluorescent Probe","volume":"91","author":"Juan","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15846","DOI":"10.1021\/ja105937q","article-title":"Hypoxia-Sensitive Fluorescent Probes for Real-Time Fluorescence Imaging of Acute Ischemia","volume":"132","author":"Kiyose","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14739","DOI":"10.1039\/C5CC05518K","article-title":"A turn-on fluorescent probe for tumor hypoxia imaging in living cells","volume":"51","author":"Cai","year":"2015","journal-title":"Chem. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21572","DOI":"10.1039\/C9RA02741F","article-title":"Novel designed azo substituted semi-cyanine fluorescent probe for cytochrome P450 reductase detection and hypoxia imaging in cancer cells","volume":"9","author":"Wang","year":"2019","journal-title":"RSC Adv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1021\/jm301804p","article-title":"Hypoxia-Selective-Alkylguanine-DNA Alkyltransferase Inhibitors: Design, Synthesis, and Evaluation of 6-(Benzyloxy)-2-(aryldiazenyl)-9-purines as Prodrugs of Benzylguanine","volume":"56","author":"Zhu","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13713","DOI":"10.1021\/jacs.7b05019","article-title":"Development of an Azo-Based Photosensitizer Activated under Mild Hypoxia for Photodynamic Therapy","volume":"139","author":"Piao","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.biomaterials.2016.11.023","article-title":"Reconsidering azobenzene as a component of small-molecule hypoxia-mediated cancer drugs: A theranostic case study","volume":"115","author":"Verwilst","year":"2017","journal-title":"Biomaterials"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4385","DOI":"10.1039\/C8TB90081G","article-title":"A ypoxia-specific and mitochondria-targeted anticancer theranostic agent with high selectivity for cancer cells","volume":"6","author":"Hu","year":"2018","journal-title":"J. Mater. Chem. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jconrel.2018.08.036","article-title":"Azo-based small molecular hypoxia responsive theranostic for tumor-specific imaging and therapy","volume":"288","author":"Zhou","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1021\/bc700394s","article-title":"A doxorubicin prodrug activated by the staudinger reaction","volume":"19","author":"Vulders","year":"2008","journal-title":"Bioconjug. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7983","DOI":"10.1039\/C8CC03430C","article-title":"An azobenzene-based heteromeric prodrug for hypoxia-activated chemotherapy by regulating subcellular localization","volume":"54","author":"Li","year":"2018","journal-title":"Chem. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.7150\/thno.36755","article-title":"An Activatable Near-Infrared Chromophore for Multispectral Optoacoustic Imaging of Tumor Hypoxia and for Tumor Inhibition","volume":"9","author":"Huang","year":"2019","journal-title":"Theranostics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/j.cclet.2021.09.013","article-title":"A near-infrared multifunctional fluorescent probe for hypoxia monitoring and tumor-targeted therapy","volume":"33","author":"Lu","year":"2022","journal-title":"Chin. Chem. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8185","DOI":"10.1021\/jacs.2c01197","article-title":"Turn-on Fluorescent Biosensors for Imaging Hypoxia-like Conditions in Living Cells","volume":"144","author":"Rivero","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"125124","DOI":"10.1016\/j.foodchem.2019.125124","article-title":"Anti-inflammatory effects of flavonoids","volume":"299","author":"Maleki","year":"2019","journal-title":"Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Choy, K.W., Murugan, D., Leong, X.F., Abas, R., Alias, A., and Mustafa, M.R. (2019). Flavonoids as Natural Anti-Inflammatory Agents Targeting Nuclear Factor-Kappa B (NF\u03baB) Signaling in Cardiovascular Diseases: A Mini Review. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01295"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104720","DOI":"10.1016\/j.fitote.2020.104720","article-title":"Antimicrobial flavonoids as a potential substitute for overcoming antimicrobial resistance","volume":"146","author":"Biharee","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11101-018-9591-z","article-title":"Comprehensive review of antimicrobial activities of plant flavonoids","volume":"18","author":"Bartoszewski","year":"2019","journal-title":"Phytochem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jff.2014.03.019","article-title":"In vitro and in vivo anti-influenza virus activities of flavonoids and related compounds as components of Brazilian propolis (AF-08)","volume":"8","author":"Kai","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kopustinskiene, D.M., Jakstas, V., Savickas, A., and Bernatoniene, J. (2020). Flavonoids as Anticancer Agents. Nutrients, 12.","DOI":"10.3390\/nu12020457"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1016\/j.biocel.2013.10.004","article-title":"Flavonoids as prospective compounds for anti-cancer therapy","volume":"45","author":"Ravishankar","year":"2013","journal-title":"Int. J. Biochem. Cell B"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ninfali, P., Antonelli, A., Magnani, M., and Scarpa, E.S. (2020). Antiviral Properties of Flavonoids and Delivery Strategies. Nutrients, 12.","DOI":"10.3390\/nu12092534"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"El-Deeb, O.S., Elesawy, R.O., Eltokhy, A.K., Al-Shenawy, H.A., Ghanem, H.B., Rizk, F.H., Barhoma, R.A., Shalaby, R.H., Abdelsattar, A.M., and Mashal, S.S. (2023). Moderating Gut Microbiome\/Mitochondrial Axis in Oxazolone Induced Ulcerative Colitis: The Evolving Role of \u03b2-Glucan and\/or, Aldose Reductase Inhibitor, Fidarestat. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032711"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1093\/ecco-jcc\/jjad006","article-title":"GATA6-AS1 Regulates Intestinal Epithelial Mitochondrial Functions, and its Reduced Expression is Linked to Intestinal Inflammation and Less Favourable Disease Course in Ulcerative Colitis","volume":"17","author":"Sosnovski","year":"2023","journal-title":"J. Crohn\u2019s Colitis"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/17\/4244\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:50:03Z","timestamp":1760111403000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/17\/4244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":31,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["molecules29174244"],"URL":"https:\/\/doi.org\/10.3390\/molecules29174244","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,6]]}}}