{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:31:24Z","timestamp":1791221484640,"version":"4.1.0"},"reference-count":110,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Glyoxalase I is a crucial target in cancer treatment due to its involvement in detoxifying methylglyoxal. Suppressing the activity of Glyoxalase I has great potential for disrupting the pathways that allow cancer cells to survive, creating a new route for cancer treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology<\/jats:title>\n<jats:p>This study aims to investigate several substances as inhibitors of glyoxalase-I. After demonstrating their efficacy, additional inquiry will concentrate on assessing their cytotoxic and anti-inflammatory capabilities, yielding significant insights for prospective medicinal uses. The selection of these chemicals as potential Glyoxalase I inhibitors was based on their ability to bind metals, in crucial enzymes. These compounds consist of catechol, dihydroxy, trihydroxy benzene, and functional groups such hydroxamic acid, sulfur, carboxylic acid, amide, and 3-hydroxy-4-pyridone with the aim to suppress Glyoxalase I <jats:italic><jats:italic>in vitro<\/jats:italic><\/jats:italic>. Docking protocol was employed to examine the binding interactions with the active site. These auspicious compounds have been subjected to cytotoxicity assay testing employing Sulforhodamine B in eleven distinct cell lines, as well as anti-inflammatory and antioxidant evaluations.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Glyoxalase I inhibition revealed that 4-hydroxy-estradiol exhibited the highest efficacy with an IC<jats:sub>50<\/jats:sub> value of 0.226 \u00b5M. Trichostatin A demonstrated a significant anti-proliferation effect in colorectal cancer cells (CACO2, HCT116, SW620, HT29) with IC<jats:sub>50<\/jats:sub> values ranging from 14.0 \u00b5M to 27.0 \u00b5M. Furthermore, it exhibited substantial decreases in viability, ranging from 1.4 \u00b5M to 14.7 \u00b5M, in cancer cell cultures of skin (A375), lung (A549), prostate (PC3), breast (MCF7 and T47D), and cervical (HeLa). Except for 4-hydroxyestrdiol, the other phytochemicals demonstrated considerable selectivity in reducing the viability of cancer cells in monolayers of colorectal, cervical, mammary, lung, and skin tissues. In comparison to indomethacin and vitamin C, all of the studied natural compounds exhibited excellent anti-inflammatory properties in LPS-primed RAW 264.7 murine macrophages and had moderate antioxidant abilities comparable to ascorbic acid, with IC<jats:sub>50<\/jats:sub> values from 26.0 \u00b5M to 99.0 \u00b5M.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Further assessment of molecular action mechanisms and structural betterments\/enhancements and\/or derivatization of promising potent agents with antiglyoxylase \u2013 antiinflammation duality along with differential cytotoxicity and reductive capacities are advisably warranted with appropriately matched downstream in vivo validation modalities.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0333405","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:34:39Z","timestamp":1760549679000},"page":"e0333405","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cytotoxic, anti-inflammatory, antioxidant, and anti-glyoxalase-I evaluation of chelating substances: In silico and in vitro study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5723-6247","authenticated-orcid":true,"given":"MohammedBashar","family":"Al-Qazzan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qosay","family":"Al-Balas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belal","family":"Alnajjar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violet","family":"Kasabri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Al-Hiari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0211-1866","authenticated-orcid":true,"given":"Aref","family":"Zayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rema","family":"AlKhateeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3842-7419","authenticated-orcid":true,"given":"Mohammed","family":"Al-Akeedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"issue":"8","key":"pone.0333405.ref001","doi-asserted-by":"crossref","first-page":"3500","DOI":"10.1158\/0008-5472.CAN-06-4626","article-title":"Cancer immunologists and cancer biologists: why we didn\u2019t talk then but need to now","volume":"67","author":"GC Prendergast","year":"2007","journal-title":"Cancer Res"},{"issue":"1","key":"pone.0333405.ref002","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"RL Siegel","year":"2023","journal-title":"CA Cancer J Clin"},{"issue":"5","key":"pone.0333405.ref003","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/0006-291X(69)90445-8","article-title":"Glyoxalase inhibitors as potential anticancer agents","volume":"35","author":"R Vince","year":"1969","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0333405.ref004","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1021\/jm00283a009","article-title":"Glyoxalase inhibitors. A possible approach to anticancer agents","volume":"14","author":"R Vince","year":"1971","journal-title":"J Med Chem"},{"issue":"10","key":"pone.0333405.ref005","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1159\/000367800","article-title":"Glyoxalase I in tumor cell proliferation and survival and as a potential target for anticancer therapy","volume":"37","author":"X Geng","year":"2014","journal-title":"Oncol Res Treat"},{"issue":"2","key":"pone.0333405.ref006","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0021-9258(18)56017-8","article-title":"The mechanism of action of glyoxalase","volume":"190","author":"E Racker","year":"1951","journal-title":"J Biol Chem"},{"key":"pone.0333405.ref007","article-title":"Functions of glutathione: biochemical, physiological, toxicological, and clinical aspects","author":"A Larsson","year":"1983","journal-title":"Proceedings of the Fifth Karolinska Institute Nobel Conference; 1982 May 23\u201327; Skokloster, Sweden. Raven Press"},{"key":"pone.0333405.ref008","first-page":"763","article-title":"The glyoxalase enigma. The biological consequences of a ubiquitous enzyme","volume":"14","author":"SJ Carrington","year":"1986","journal-title":"IRCS Med Sci"},{"issue":"18","key":"pone.0333405.ref009","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.1021\/bi00232a031","article-title":"Kinetic parameters for the elimination reaction catalyzed by triosephosphate isomerase and an estimation of the reaction\u2019s physiological significance","volume":"30","author":"JP Richard","year":"1991","journal-title":"Biochemistry"},{"key":"pone.0333405.ref010","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0009-2797(97)00157-9","article-title":"Glutathione-dependent detoxification of alpha-oxoaldehydes by the glyoxalase system: involvement in disease mechanisms and antiproliferative activity of glyoxalase I inhibitors","author":"PJ Thornalley","year":"1998","journal-title":"Chem Biol Interact"},{"key":"pone.0333405.ref011","doi-asserted-by":"crossref","first-page":"110663","DOI":"10.1016\/j.biopha.2020.110663","article-title":"Glyoxalase system: a systematic review of its biological activity, related-diseases, screening methods and small molecule regulators","volume":"131","author":"Y He","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"pone.0333405.ref012","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3389\/fonc.2019.00785","article-title":"Inhibition of glyoxalase-I leads to reduced proliferation, migration and colony formation, and enhanced susceptibility to sorafenib in hepatocellular carcinoma","volume":"9","author":"M Michel","year":"2019","journal-title":"Front Oncol"},{"issue":"1","key":"pone.0333405.ref013","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3390\/ijms22010310","article-title":"Glyoxalase system in the progression of skin aging and skin malignancies","volume":"22","author":"S Yumnam","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"12","key":"pone.0333405.ref014","doi-asserted-by":"crossref","first-page":"869","DOI":"10.14348\/molcells.2022.0109","article-title":"Glyoxalase 1 as a therapeutic target in cancer and cancer stem cells","volume":"45","author":"J-Y Kim","year":"2022","journal-title":"Mol Cells"},{"key":"pone.0333405.ref015","doi-asserted-by":"crossref","first-page":"748698","DOI":"10.3389\/fonc.2021.748698","article-title":"Studies of glyoxalase 1-linked multidrug resistance reveal glycolysis-derived reactive metabolite, methylglyoxal, is a common contributor in cancer chemotherapy targeting the spliceosome","volume":"11","author":"M Alhujaily","year":"2021","journal-title":"Front Oncol"},{"issue":"1","key":"pone.0333405.ref016","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s42004-023-00864-y","article-title":"Development of pathway-oriented screening to identify compounds to control 2-methylglyoxal metabolism in tumor cells","volume":"6","author":"K Yanagi","year":"2023","journal-title":"Commun Chem"},{"key":"pone.0333405.ref017","doi-asserted-by":"crossref","first-page":"657599","DOI":"10.3389\/fchem.2021.657599","article-title":"Cellular basis of organotin(IV) derivatives as anticancer metallodrugs: a review","volume":"9","author":"SN Syed Annuar","year":"2021","journal-title":"Front Chem"},{"key":"pone.0333405.ref018","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.2147\/DDDT.S110997","article-title":"Novel glyoxalase-I inhibitors possessing a \u201czinc-binding feature\u201d as potential anticancer agents","volume":"10","author":"QA Al-Balas","year":"2016","journal-title":"Drug Des Devel Ther"},{"issue":"8","key":"pone.0333405.ref019","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.3390\/cells10081852","article-title":"The glyoxalase system in age-related diseases: nutritional intervention as anti-ageing strategy","volume":"10","author":"G Aragon\u00e8s","year":"2021","journal-title":"Cells"},{"issue":"4","key":"pone.0333405.ref020","doi-asserted-by":"crossref","first-page":"115243","DOI":"10.1016\/j.bmc.2019.115243","article-title":"Recent advances in the discovery and development of glyoxalase I inhibitors","volume":"28","author":"T Jin","year":"2020","journal-title":"Bioorg Med Chem"},{"issue":"9","key":"pone.0333405.ref021","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s10822-019-00226-8","article-title":"Discovery of a nanomolar inhibitor of the human glyoxalase-I enzyme using structure-based poly-pharmacophore modelling and molecular docking","volume":"33","author":"NA Al-Shar\u2019i","year":"2019","journal-title":"J Comput Aided Mol Des"},{"issue":"1","key":"pone.0333405.ref022","first-page":"25","article-title":"Design, synthesis and biological evaluation of potential novel zinc binders targeting human glyoxalase-I; a validated target for cancer treatment","volume":"11","author":"QA Al-Balas","year":"2018","journal-title":"Jordan J Pharm Sci"},{"key":"pone.0333405.ref023","doi-asserted-by":"crossref","first-page":"105657","DOI":"10.1016\/j.bioorg.2022.105657","article-title":"Lead optimization and biological evaluation of diazenylbenzenesulfonamides inhibitors against glyoxalase-I enzyme as potential anticancer agents","volume":"120","author":"BA Al-Oudat","year":"2022","journal-title":"Bioorg Chem"},{"key":"pone.0333405.ref024","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0531-5131(02)00884-1","article-title":"Novel anti-glycation therapeutic agents: glyoxalase I mimetics","volume":"1245","author":"S Battah","year":"2002","journal-title":"Int Congr Ser"},{"issue":"10","key":"pone.0333405.ref025","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1007\/s00044-024-03289-x","article-title":"Structural optimization and biological evaluation of quinoline\/naphthalene-based glyoxalase-I inhibitors as anti-cancer candidates","volume":"33","author":"BA Al-Oudat","year":"2024","journal-title":"Med Chem Res"},{"key":"pone.0333405.ref026","first-page":"21","article-title":"Unraveling potential glyoxalase-I inhibitors utilizing structure-based drug design techniques","volume":"17","author":"MH Fetian","year":"2024","journal-title":"Adv Appl Bioinform Chem"},{"issue":"1","key":"pone.0333405.ref027","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.immuni.2019.06.025","article-title":"Inflammation and cancer: triggers, mechanisms, and consequences","volume":"51","author":"FR Greten","year":"2019","journal-title":"Immunity"},{"key":"pone.0333405.ref028","doi-asserted-by":"crossref","DOI":"10.1007\/978-981-15-9411-3_12","article-title":"Oxidative stress and glyoxalase pathway in cancer.","author":"NAB. Tiku","year":"2022","journal-title":"Handbook of oxidative stress in cancer: mechanistic aspects. Singapore: Springer"},{"issue":"1","key":"pone.0333405.ref029","doi-asserted-by":"crossref","first-page":"101138","DOI":"10.1016\/j.esmoop.2023.101138","article-title":"101P Pharmacological inhibition of glyoxalase-1 as novel therapeutic strategy to enhance trabectedin anti-tumor effect in soft tissue sarcoma preclinical models","volume":"8","author":"B Vincenzi","year":"2023","journal-title":"ESMO Open"},{"issue":"1","key":"pone.0333405.ref030","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s13045-021-01187-y","article-title":"Neutrophils in cancer carcinogenesis and metastasis","volume":"14","author":"S Xiong","year":"2021","journal-title":"J Hematol Oncol"},{"issue":"6","key":"pone.0333405.ref031","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/onc.2009.421","article-title":"The role of COX-2 in intestinal inflammation and colorectal cancer","volume":"29","author":"D Wang","year":"2010","journal-title":"Oncogene"},{"issue":"12","key":"pone.0333405.ref032","doi-asserted-by":"crossref","first-page":"4047","DOI":"10.31557\/APJCP.2022.23.12.4047","article-title":"Selected statins as dual antiproliferative-antiinflammatory compounds","volume":"23","author":"B Haj Hussein","year":"2022","journal-title":"Asian Pac J Cancer Prev"},{"key":"pone.0333405.ref033","doi-asserted-by":"crossref","first-page":"564674","DOI":"10.3389\/fonc.2020.564674","article-title":"Emodin inhibits inflammation, carcinogenesis, and cancer progression in the AOM\/DSS model of colitis-associated intestinal tumorigenesis","volume":"10","author":"Y Zhang","year":"2021","journal-title":"Front Oncol"},{"key":"pone.0333405.ref034","article-title":"Unique bidentate chelators of functionalized heterocyclic fluoroquinolones with dual anti-inflammation and selective cytotoxicity via C7-C8 ethylene diamine bridge","author":"M Alzghoul","year":"2025","journal-title":"Curr Med Chem"},{"issue":"7","key":"pone.0333405.ref035","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.3390\/ijms18071544","article-title":"Correlation between oxidative stress, nutrition, and cancer initiation","volume":"18","author":"SK Saha","year":"2017","journal-title":"Int J Mol Sci"},{"issue":"12","key":"pone.0333405.ref036","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"D Furman","year":"2019","journal-title":"Nat Med"},{"issue":"40","key":"pone.0333405.ref037","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.2174\/1381612825666190215121712","article-title":"Oxidative stress and cancer","volume":"24","author":"JE Klaunig","year":"2018","journal-title":"Curr Pharm Des"},{"key":"pone.0333405.ref038","doi-asserted-by":"crossref","first-page":"9965916","DOI":"10.1155\/2021\/9965916","article-title":"The involvement of the oxidative stress status in cancer pathology: a double view on the role of the antioxidants","volume":"2021","author":"KF Zahra","year":"2021","journal-title":"Oxid Med Cell Longev"},{"issue":"12","key":"pone.0333405.ref039","doi-asserted-by":"crossref","first-page":"7619","DOI":"10.21037\/tcr-20-2359","article-title":"Functions of polyphenols and its anticancer properties in biomedical research: a narrative review","volume":"9","author":"PB Bhosale","year":"2020","journal-title":"Transl Cancer Res"},{"issue":"12","key":"pone.0333405.ref040","doi-asserted-by":"crossref","first-page":"6185","DOI":"10.1021\/acs.jcim.0c00730","article-title":"Antioxidant and anticancer properties of functionalized ferrocene with hydroxycinnamate derivatives-an integrated experimental and theoretical study","volume":"60","author":"L Tabrizi","year":"2020","journal-title":"J Chem Inf Model"},{"issue":"12","key":"pone.0333405.ref041","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.3390\/antiox9121188","article-title":"Oxidative stress-inducing anticancer therapies: taking a closer look at their immunomodulating effects","volume":"9","author":"J Van Loenhout","year":"2020","journal-title":"Antioxidants (Basel)"},{"issue":"5","key":"pone.0333405.ref042","doi-asserted-by":"crossref","first-page":"642","DOI":"10.3390\/antiox10050642","article-title":"Oxidative stress in cancer cell metabolism","volume":"10","author":"S Arfin","year":"2021","journal-title":"Antioxidants (Basel)"},{"issue":"3","key":"pone.0333405.ref043","doi-asserted-by":"crossref","DOI":"10.5530\/pj.2021.13.99","article-title":"Evaluation of antioxidant and anticancer activity of Myristica fragrans Houtt. bark","volume":"13","author":"B Ginting","year":"2021","journal-title":"Pharmacogn J"},{"issue":"2","key":"pone.0333405.ref044","first-page":"1","article-title":"Antioxidant stress and anticancer activity of peptide\u2011chelated selenium in vitro","volume":"48","author":"X Li","year":"2021","journal-title":"Int J Mol Med"},{"issue":"1","key":"pone.0333405.ref045","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1515\/chem-2021-0042","article-title":"Comparative study of antioxidant and anticancer activities and HPTLC quantification of rutin in white radish (Raphanus sativus L.) leaves and root extracts grown in Saudi Arabia","volume":"19","author":"OM Noman","year":"2021","journal-title":"Open Chem"},{"issue":"7","key":"pone.0333405.ref046","first-page":"409","article-title":"Anticancer and antioxidant activities of l-asparaginase produced by local Weissella paramesenteroides MN2C2 strain","volume":"65","author":"MN Amer","year":"2022","journal-title":"Egypt J Chem"},{"issue":"9","key":"pone.0333405.ref047","doi-asserted-by":"crossref","DOI":"10.1111\/jfbc.14249","article-title":"Antioxidative, anti-inflammatory, and anticancer properties of the red biopigment extract from Monascus purpureus (MTCC 369)","volume":"46","author":"V Chaudhary","year":"2022","journal-title":"J Food Biochem"},{"issue":"4","key":"pone.0333405.ref048","doi-asserted-by":"crossref","first-page":"1","DOI":"10.53293\/jasn.2021.3890.1054","article-title":"Developing strategy for a successful antioxidant, anticancer activity via an improved method prepared to porous silicon nanoparticles","volume":"1","author":"KH Jawad","year":"2021","journal-title":"J Appl Sci Nanotechnol"},{"issue":"4","key":"pone.0333405.ref049","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.biocel.2008.05.026","article-title":"Zn(II)-dependent histone deacetylase inhibitors: suberoylanilide hydroxamic acid and trichostatin A","volume":"41","author":"R Codd","year":"2009","journal-title":"Int J Biochem Cell Biol"},{"issue":"16","key":"pone.0333405.ref050","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1039\/DT9940002347","article-title":"Acetazolamide binding to zinc(II), cobalt(II) and copper(II) model complexes of carbonic anhydrase","author":"G Alzuet","year":"1994","journal-title":"J Chem Soc Dalt Trans"},{"issue":"12","key":"pone.0333405.ref051","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1211\/002235702261","article-title":"Aspirin and sodium salicylate inhibit proliferation and induce apoptosis in rheumatoid synovial cells","volume":"54","author":"R Yamazaki","year":"2002","journal-title":"J Pharm Pharmacol"},{"issue":"9","key":"pone.0333405.ref052","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.3390\/molecules27092816","article-title":"1-Hydroxy-2(1H)-pyridinone-based chelators with potential catechol O-Methyl transferase inhibition and neurorescue dual action against Parkinson\u2019s disease","volume":"27","author":"JCJ Bergin","year":"2022","journal-title":"Molecules"},{"issue":"1","key":"pone.0333405.ref053","doi-asserted-by":"crossref","first-page":"87","DOI":"10.25122\/jml-2023-0257","article-title":"Novel anthraquinone amide derivatives as potential glyoxalase-I inhibitors","volume":"17","author":"M Al-Akeedi","year":"2024","journal-title":"J Med Life"},{"issue":"2","key":"pone.0333405.ref054","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/ddr.21421","article-title":"Computational and experimental exploration of the structure-activity relationships of flavonoids as potent glyoxalase-I inhibitors","volume":"79","author":"QA Al-Balas","year":"2018","journal-title":"Drug Dev Res"},{"issue":"11","key":"pone.0333405.ref055","first-page":"1324","article-title":"Novel thiazole carboxylic acid derivatives possessing a \u201czinc binding feature\u201d as potential human glyoxalase-I inhibitors","volume":"14","author":"QA Al-Balasa","year":"2017","journal-title":"LDDD"},{"issue":"4","key":"pone.0333405.ref056","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2174\/1389557518666181009141231","article-title":"Recent advances in glyoxalase-I inhibition","volume":"19","author":"QA Al-Balas","year":"2019","journal-title":"Mini Rev Med Chem"},{"issue":"16","key":"pone.0333405.ref057","doi-asserted-by":"crossref","first-page":"115608","DOI":"10.1016\/j.bmc.2020.115608","article-title":"Design, synthesis and biological evaluation of novel glyoxalase I inhibitors possessing diazenylbenzenesulfonamide moiety as potential anticancer agents","volume":"28","author":"BA Al-Oudat","year":"2020","journal-title":"Bioorg Med Chem"},{"key":"pone.0333405.ref058","doi-asserted-by":"crossref","first-page":"873","DOI":"10.2147\/DDDT.S356621","article-title":"Design, synthesis and biological evaluation of 1,4-benzenesulfonamide derivatives as glyoxalase I inhibitors","volume":"16","author":"SA Audat","year":"2022","journal-title":"Drug Des Devel Ther"},{"issue":"1","key":"pone.0333405.ref059","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/spmg.19885","article-title":"Cell lines: valuable tools or useless artifacts","volume":"2","author":"G Kaur","year":"2012","journal-title":"Spermatogenesis"},{"issue":"3","key":"pone.0333405.ref060","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B colorimetric assay for cytotoxicity screening","volume":"1","author":"V Vichai","year":"2006","journal-title":"Nat Protoc"},{"issue":"6","key":"pone.0333405.ref061","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1111\/cbdd.13049","article-title":"Antilipase and antiproliferative activities of novel fluoroquinolones and triazolofluoroquinolones","volume":"90","author":"S Arabiyat","year":"2017","journal-title":"Chem Biol Drug 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Piazzini","year":"2019","journal-title":"Molecules"},{"issue":"14","key":"pone.0333405.ref068","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.1073\/pnas.1101143108","article-title":"Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis","volume":"108","author":"H-H Hoffmann","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"pone.0333405.ref069","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.31557\/APJCP.2019.20.8.2503","article-title":"Dual glycation-inflammation modulation, DPP-IV and pancraetic lipase inhibitory potentials and antiproliferative activity of novel fluoroquinolones","volume":"20","author":"S Arabiyat","year":"2019","journal-title":"Asian Pac J Cancer Prev"},{"issue":"2","key":"pone.0333405.ref070","doi-asserted-by":"crossref","first-page":"402","DOI":"10.35516\/jjps.v16i2.1467","article-title":"Metal chelators as anticancer approach: Part I; novel 7-anisidine derivatives with multidentate at 7-8 carbons of fluoroquinolone scaffold as potential chelator anticancer and antilipolytic candidates","volume":"16","author":"Y Al-Hiari","year":"2023","journal-title":"Jordan J Pharm Sci"},{"issue":"3","key":"pone.0333405.ref071","doi-asserted-by":"crossref","first-page":"977","DOI":"10.31557\/APJCP.2023.24.3.977","article-title":"Preparation and characterization of rutin-encapsulated polymeric micelles and studies of synergism with bioactive benzoic acids and triazolofluoroquinolones as anticancer nanomedicines","volume":"24","author":"R Ibrahim","year":"2023","journal-title":"Asian Pac J Cancer Prev"},{"issue":"3","key":"pone.0333405.ref072","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4103\/jpbs.jpbs_311_22","article-title":"Preparation and characterization of capsaicin encapsulated polymeric micelles and studies of synergism with nicotinic acids as potential anticancer nanomedicines","volume":"15","author":"R Shamsheer","year":"2023","journal-title":"J Pharm Bioallied 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Elsevier"},{"key":"pone.0333405.ref075","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2022.905755","article-title":"Review of shikonin and derivatives: isolation, chemistry, biosynthesis, pharmacology and toxicology","volume":"13","author":"S Yadav","year":"2022","journal-title":"Front Pharmacol"},{"key":"pone.0333405.ref076","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.taap.2016.04.009","article-title":"Comparison of the inhibitory effects of tolcapone and entacapone against human UDP-glucuronosyltransferases","volume":"301","author":"X Lv","year":"2016","journal-title":"Toxicol Appl Pharmacol"},{"issue":"5","key":"pone.0333405.ref077","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.3390\/ijms20051162","article-title":"Histone deacetylase inhibitor, trichostatin A, synergistically enhances paclitaxel-induced cytotoxicity in urothelial carcinoma cells by suppressing the ERK pathwasy","volume":"20","author":"F-S Hsu","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"7","key":"pone.0333405.ref078","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.3390\/molecules27072183","article-title":"Calceolarioside A, a phenylpropanoid glycoside from Calceolaria spp., displays antinociceptive and anti-inflammatory properties","volume":"27","author":"S Pieretti","year":"2022","journal-title":"Molecules"},{"issue":"8","key":"pone.0333405.ref079","doi-asserted-by":"crossref","first-page":"10255","DOI":"10.1021\/acsomega.8b00706","article-title":"Activity of coii-quinalizarin: a novel analogue of anthracycline-based anticancer agents targets human DNA topoisomerase, whereas quinalizarin itself acts via formation of semiquinone on acute lymphoblastic leukemia MOLT-4 and HCT 116 cells","volume":"3","author":"S Mukherjee Chatterjee","year":"2018","journal-title":"ACS Omega"},{"issue":"2","key":"pone.0333405.ref080","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1021\/np060476h","article-title":"Structures, biogenesis, and biological activities of pyrano [4, 3-c] isochromen-4-one derivatives from the fungus Phellinus igniarius","volume":"70","author":"Y Wang","year":"2007","journal-title":"J Nat Prod"},{"issue":"16","key":"pone.0333405.ref081","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1016\/j.bmcl.2015.05.081","article-title":"Anti-influenza activities of polyphenols from the medicinal mushroom Phellinus baumii","volume":"25","author":"BS Hwang","year":"2015","journal-title":"Bioorg Med Chem Lett"},{"issue":"6","key":"pone.0333405.ref082","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/BF02980159","article-title":"An antioxidant hispidin from the mycelial cultures of Phellinus linteus","volume":"27","author":"I-H Park","year":"2004","journal-title":"Arch Pharm Res"},{"issue":"12","key":"pone.0333405.ref083","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1002\/jsfa.6978","article-title":"Anti-inflammatory activity of mushroom-derived hispidin through blocking of NF-\u03baB activation","volume":"95","author":"HJ Shao","year":"2015","journal-title":"J Sci Food Agric"},{"key":"pone.0333405.ref084","first-page":"1167","article-title":"Thermodynamic and kinetic assessment of cobalt II adsorption using green synthesized NiO\/\u03b3-Al2O3 nanoparticles","volume":"4","author":"KH Hassan","year":"2025","journal-title":"Salud, Cienc Tecnol - Ser Conf"},{"issue":"8","key":"pone.0333405.ref085","first-page":"4087","article-title":"Anticancer activity of hispidin via reactive oxygen species-mediated apoptosis in colon cancer cells","volume":"34","author":"J-H Lim","year":"2014","journal-title":"Anticancer Res"},{"issue":"2","key":"pone.0333405.ref086","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1089\/jmf.2018.4267","article-title":"Antiallergic activity of the wild mushrooms of Nepal and the pure compound hispidin","volume":"22","author":"S Tamrakar","year":"2019","journal-title":"J Med Food"},{"issue":"4","key":"pone.0333405.ref087","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2174\/1573406417666210714170403","article-title":"Identification of the first \u201cTwo Digit Nano-molar\u201d inhibitors of the human glyoxalase-I enzyme as potential anticancer agents","volume":"18","author":"QA Al-Balas","year":"2022","journal-title":"Med Chem"},{"issue":"3","key":"pone.0333405.ref088","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s00044-019-02486-3","article-title":"Discovery of a nanomolar glyoxalase-I inhibitor using integrated ligand-based pharmacophore modeling and molecular docking","volume":"29","author":"NA Al-Shar\u2019i","year":"2019","journal-title":"Med Chem Res"},{"issue":"1","key":"pone.0333405.ref089","doi-asserted-by":"crossref","first-page":"118","DOI":"10.22159\/ijcpr.2017v9i1.16633","article-title":"Study of binding interactions of human carbonic anhydrase XII","volume":"9","author":"H Barua","year":"2016","journal-title":"Int J Curr Pharm Sci"},{"key":"pone.0333405.ref090","article-title":"The investigation of Nf\u03bab inhibitors to block cell proliferation in OSCC cells lines","author":"Y Cheng","year":"2024","journal-title":"Curr Med Chem"},{"key":"pone.0333405.ref091","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14740338.2024.2396387","article-title":"Clinical features, treatment, and prognosis of SGLT2 inhibitors induced acute pancreatitis","volume":"4","author":"R Li","year":"2024","journal-title":"Expert Opin Drug Saf"},{"issue":"4","key":"pone.0333405.ref092","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s11030-018-9839-y","article-title":"Structure\u2013activity relationship investigation of coumarin\u2013chalcone hybrids with diverse side-chains as acetylcholinesterase and butyrylcholinesterase inhibitors","volume":"22","author":"L Kang","year":"2018","journal-title":"Mol Divers"},{"key":"pone.0333405.ref093","doi-asserted-by":"crossref","first-page":"112828","DOI":"10.1016\/j.biopha.2022.112828","article-title":"Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) A.C. Sm. by UHPLC-Q-Exactive Orbitrap Mass spectrometry and assessment of their antioxidant and anti-inflammatory activities","volume":"149","author":"S Shi","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"pone.0333405.ref094","doi-asserted-by":"crossref","first-page":"119126","DOI":"10.1016\/j.jep.2024.119126","article-title":"Chrysotoxine regulates ferroptosis and the PI3K\/AKT\/mTOR pathway to prevent cervical cancer","volume":"338","author":"J Zhou","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"pone.0333405.ref095","doi-asserted-by":"crossref","first-page":"100413","DOI":"10.1016\/j.fbr.2025.100413","article-title":"Current research on the medical importance of Trametes species","volume":"51","author":"RS Lodi","year":"2025","journal-title":"Fung Biol Rev"},{"issue":"11","key":"pone.0333405.ref096","article-title":"Development of a high-speed and ultrasensitive UV\/Vis-CM for detecting total triterpenes in traditional Chinese medicine and its application","volume":"10","author":"Y Guo","year":"2024","journal-title":"Heliyon"},{"key":"pone.0333405.ref097","doi-asserted-by":"crossref","first-page":"119191","DOI":"10.1016\/j.indcrop.2024.119191","article-title":"Ant colony algorithm-enabled back propagation neural network and response surface methodology based ultrasonic optimization of safflower seed alkaloid extraction and antioxidant","volume":"220","author":"H Wan","year":"2024","journal-title":"Industr Crops Prod"},{"issue":"33","key":"pone.0333405.ref098","doi-asserted-by":"crossref","first-page":"54838","DOI":"10.18632\/oncotarget.18601","article-title":"Synergistic inhibition of colon cancer growth by the combination of methylglyoxal and silencing of glyoxalase I mediated by the STAT1 pathway","volume":"8","author":"Y Chen","year":"2017","journal-title":"Oncotarget"},{"issue":"5","key":"pone.0333405.ref099","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.1007\/s00210-024-03544-3","article-title":"Unlocking the biological potential of methyl antcinate A: a new frontier in cancer and inflammation application","volume":"398","author":"M Sharif","year":"2025","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"4","key":"pone.0333405.ref100","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41419-023-05786-0","article-title":"Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways","volume":"14","author":"Z Xie","year":"2023","journal-title":"Cell Death Dis"},{"issue":"1","key":"pone.0333405.ref101","first-page":"2880","article-title":"Correlation of plasma and salivary osteocalcin levels with nascent metabolic syndrome components with and without pre\/diabetes biochemical parameters","volume":"22","author":"NR Bulatova","year":"2024","journal-title":"Pharm Pract"},{"key":"pone.0333405.ref102","doi-asserted-by":"crossref","first-page":"129087","DOI":"10.1016\/j.bmcl.2022.129087","article-title":"Design and synthesis of dual cathepsin L and S inhibitors and antimetastatic activity evaluation in pancreatic cancer cells","volume":"80","author":"H Huang","year":"2023","journal-title":"Bioorg Med Chem Lett"},{"key":"pone.0333405.ref103","doi-asserted-by":"crossref","first-page":"117987","DOI":"10.1016\/j.bmc.2024.117987","article-title":"Synthesis of \u03b1-fluorocinnamate derivatives as novel cathepsin S inhibitors with in vitro antiproliferative activity against pancreatic cancer cells","volume":"115","author":"A Citarella","year":"2024","journal-title":"Bioorg Med Chem"},{"issue":"8","key":"pone.0333405.ref104","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3390\/metabo12080704","article-title":"Salivary concentrations of chemerin, \u03b1-defensin 1, and TNF-\u03b1 as potential biomarkers in the early diagnosis of colorectal cancer","volume":"12","author":"D Waniczek","year":"2022","journal-title":"Metabolites"},{"issue":"15","key":"pone.0333405.ref105","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.2174\/0109298673263854231009063053","article-title":"Synthesis and selective anticancer activity evaluation of 2-phenylacrylonitrile derivatives as tubulin inhibitors","volume":"31","author":"Y-Z Jin","year":"2024","journal-title":"Curr Med Chem"},{"issue":"4","key":"pone.0333405.ref106","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1021\/bi001603q","article-title":"An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7","volume":"40","author":"S Shin","year":"2001","journal-title":"Biochemistry"},{"issue":"9","key":"pone.0333405.ref107","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1007\/s00262-020-02559-y","article-title":"Rapid noninvasive detection of bladder cancer using survivin antibody-conjugated gold nanoparticles (GNPs) based on localized surface plasmon resonance (LSPR)","volume":"69","author":"MH Jazayeri","year":"2020","journal-title":"Cancer Immunol Immunother"},{"issue":"1","key":"pone.0333405.ref108","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.ejphar.2010.09.085","article-title":"Cisplatin-induced cardiotoxicity: mechanisms and cardioprotective strategies","volume":"650","author":"E-SE El-Awady","year":"2011","journal-title":"Eur J Pharmacol"},{"issue":"12","key":"pone.0333405.ref109","doi-asserted-by":"crossref","first-page":"111292","DOI":"10.1016\/j.isci.2024.111292","article-title":"Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice","volume":"27","author":"A Ghosh","year":"2024","journal-title":"iScience"},{"key":"pone.0333405.ref110","doi-asserted-by":"crossref","first-page":"831168","DOI":"10.3389\/fimmu.2022.831168","article-title":"Regulation of SIRT1 and its roles in inflammation","volume":"13","author":"Y Yang","year":"2022","journal-title":"Front 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