{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:01:21Z","timestamp":1775235681475,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T00:00:00Z","timestamp":1567555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Glyoxalase-I (Glo-I) enzyme was established to be a valid target for anticancer drug design. It performs the essential detoxification step of harmful byproducts, especially methylglyoxal. A robust computer-aided drug design approach was used to design and validate a series of compounds with selenium or sulfur based heterorings. A series of in-house multi-armed 1,2,3-selenadiazole and 1,2,3-thiadiazole benzene derivatives were tested for their Glo-I inhibitory activity. Results showed that these compounds bind Glo-I active sites competitively with strong potential to inhibit this enzyme with IC50 values in micro-molar concentration. Docking poses revealed that these compounds interact with the zinc atom at the bottom of the active site, which plays an essential role in its viability.<\/jats:p>","DOI":"10.3390\/molecules24183210","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T03:22:36Z","timestamp":1567653756000},"page":"3210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Multi-Armed 1,2,3-Selenadiazole and 1,2,3-Thiadiazole Benzene Derivatives as Novel Glyoxalase-I Inhibitors"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8350-900X","authenticated-orcid":false,"given":"Qosay A.","family":"Al-Balas","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mousa L.","family":"Al-Smadi","sequence":"additional","affiliation":[{"name":"Department of Applied Chemical Sciences, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad A.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghazi A.","family":"Al Jabal","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7804-3313","authenticated-orcid":false,"given":"Ammar M.","family":"Almaaytah","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-5099","authenticated-orcid":false,"given":"Karem H.","family":"Alzoubi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.2147\/DDDT.S86054","article-title":"Synthesis, antimicrobial and in vitro antitumor activities of a series of 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives","volume":"9","author":"Mhaidat","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"957","DOI":"10.3390\/91100957","article-title":"New 1,2,3-Selenadiazole and 1,2,3-Thiadiazole Derivatives","volume":"9","author":"Ratrout","year":"2004","journal-title":"Molecules"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S1053-4296(03)00024-9","article-title":"Trends and advances in cancer survivorship research: challenge and opportunity","volume":"13","author":"Aziz","year":"2003","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.semcdb.2011.02.013","article-title":"Glyoxalase in ageing","volume":"22","author":"Xue","year":"2011","journal-title":"Semin. Cell. Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj2690001","article-title":"The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life","volume":"269","author":"Thornalley","year":"1990","journal-title":"Biochem. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13480","DOI":"10.1021\/bi990696c","article-title":"Reaction Mechanism of Glyoxalase I Explored by an X-ray Crystallographic Analysis of the Human Enzyme in Complex with a Transition State Analogue","volume":"38","author":"Cameron","year":"1999","journal-title":"Biochemistry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1432-1033.1993.tb17638.x","article-title":"The formation of methylglyoxal from triose phosphates. Investigation using a specific assay for methylglyoxal","volume":"212","author":"Phillips","year":"1993","journal-title":"Eur. J. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1023\/A:1010632919129","article-title":"Expression of glyoxalase I and II in normal and breast cancer tissues","volume":"66","author":"Rulli","year":"2001","journal-title":"Breast Cancer Res. Treat"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrc1478","article-title":"Why do cancers have high aerobic glycolysis?","volume":"4","author":"Gatenby","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nrc2817","article-title":"Targeting metabolic transformation for cancer therapy","volume":"10","author":"Tennant","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","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":"Geng","year":"2014","journal-title":"Oncol. Res. Treat"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.semcdb.2011.02.006","article-title":"Glyoxalase in tumourigenesis and multidrug resistance","volume":"22","author":"Thornalley","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1016\/S0959-8049(02)00236-8","article-title":"Differing expression of enzymes of the glyoxalase system in superficial and invasive bladder carcinomas","volume":"38","author":"Mearini","year":"2002","journal-title":"Eur. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1038\/onc.2014.57","article-title":"Integrated genomic and functional analyses reveal glyoxalase I as a novel metabolic oncogene in human gastric cancer","volume":"34","author":"Hosoda","year":"2015","journal-title":"Oncogene"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cheng, W.-L., Tsai, M.-M., Tsai, C.-Y., Huang, Y.-H., Chen, C.-Y., Chi, H.-C., Tseng, Y.-H., Chao, I.-W., Lin, W.-C., and Wu, S.-M. (2012). Glyoxalase-I is a novel prognosis factor associated with gastric cancer progression. PLoS ONE, 7.","DOI":"10.1371\/annotation\/5e2c310d-9811-4d81-a8d5-2701953f2f46"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1002\/elps.201300497","article-title":"Proteomic analysis indicates that overexpression and nuclear translocation of lactoylglutathionelyase (GLO1) is associated with tumor progression in murine fibrosarcoma","volume":"35","author":"Wang","year":"2014","journal-title":"Electrophoresis"},{"key":"ref_17","first-page":"3219","article-title":"Glyoxalase I (GLO1) is up-regulated in pancreatic cancerous tissues compared with related non-cancerous tissues","volume":"32","author":"Wang","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_18","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":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1002\/pros.23431","article-title":"High-Level Glyoxalase 1 (GLO1) expression is linked to poor prognosis in prostate cancer","volume":"77","author":"Burdelski","year":"2017","journal-title":"Prostate"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/j.1447-0756.2011.01839.x","article-title":"Metformin sensitizes endometrial cancer cells to chemotherapy by repressing glyoxalase I expression","volume":"38","author":"Dong","year":"2012","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_21","first-page":"1","article-title":"Identification of Possible Glyoxalase II Inhibitors as Anticancer Agents by a Customized 3D Structure-Based Pharmacophore Model","volume":"108","author":"Hassan","year":"2015","journal-title":"Jordan J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18338","DOI":"10.1523\/JNEUROSCI.1249-11.2011","article-title":"Role of the glyoxalase system in astrocyte-mediated neuroprotection","volume":"31","author":"Belanger","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s00240-002-0244-7","article-title":"A possible regulatory role of glyoxalase I in cell viability of human prostate cancer","volume":"30","author":"Davidson","year":"2002","journal-title":"Urol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1021\/jm900382u","article-title":"Inhibition of glyoxalase I: the first low-nanomolar tight-binding inhibitors","volume":"52","author":"More","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1016\/j.bmcl.2006.12.056","article-title":"Design, synthesis, and binding studies of bidentate Zn-chelating peptidic inhibitors of glyoxalase-I","volume":"17","author":"More","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6039","DOI":"10.1016\/j.bmcl.2006.08.121","article-title":"A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I","volume":"16","author":"More","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Santel, T., Pflug, G., Hemdan, N.Y., Schafer, A., Hollenbach, M., Buchold, M., Hintersdorf, A., Lindner, I., Otto, A., and Bigl, M. (2008). Curcumin inhibits glyoxalase 1: A possible link to its anti-inflammatory and anti-tumor activity. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003508"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1016\/j.bmc.2008.01.031","article-title":"Structure\u2013activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects","volume":"16","author":"Takasawa","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7029","DOI":"10.1016\/j.bmc.2010.08.012","article-title":"Delphinidin, a dietary anthocyanidin in berry fruits, inhibits human glyoxalase I","volume":"18","author":"Takasawa","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13740","DOI":"10.3390\/molecules171213740","article-title":"Generation of the First Structure-Based Pharmacophore Model Containing a Selective \u201cZinc Binding Group\u201d Feature to Identify Potential Glyoxalase-1 Inhibitors","volume":"17","author":"Hassan","year":"2012","journal-title":"Molecules"},{"key":"ref_31","first-page":"58","article-title":"Computational and experimental exploration of the structure\u2013activity relationships of flavonoids as potent glyoxalase-I inhibitors","volume":"79","author":"Hassan","year":"2017","journal-title":"Drug Dev. Res."},{"key":"ref_32","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":"Qosay","year":"2017","journal-title":"Lett. Drug Des. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/jhet.5570340243","article-title":"Multiple 1,2,3-Thiadiazoles","volume":"34","author":"Hanold","year":"1997","journal-title":"J. Heterocycl. Chem. A"},{"key":"ref_34","first-page":"2357","article-title":"Multi-Arm 1,2,3-Thiadiazole Systems","volume":"11","author":"Meier","year":"1997","journal-title":"Liebigs Ann. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.3390\/10091126","article-title":"New Multi-1,2,3-Selenadiazole Aromatic Derivatives","volume":"10","author":"Ratrout","year":"2005","journal-title":"Molecules"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/18\/3210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:16:37Z","timestamp":1760188597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/18\/3210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,4]]},"references-count":35,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["molecules24183210"],"URL":"https:\/\/doi.org\/10.3390\/molecules24183210","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,4]]}}}