{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T13:45:20Z","timestamp":1761486320751,"version":"build-2065373602"},"reference-count":32,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistrySelect"],"published-print":{"date-parts":[[2018,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Despite there being significant advances in colorectal cancer (CRC) treatments, recurrence and chemoresistance remain a challenge in the treatment of patients. During the process of autophagy, cancer cells acquire anoikis resistance and escape chemotherapy. High Mobility Group Box 1 (HMGB1) protein is a key mediator of autophagy and can be exploited to develop effective targeted anticancer therapies. Gabexate mesilate (GM) used in the treatment of pancreatitis is both a synthetic inhibitor of HMGB1 and of metastasis. Structural analogues of GM hold promise to suppress HMGB1 functionality to arrest cancer growth, recurrence and resistance mechanisms. We synthesized structural GM mimetics (GMMs) and evaluated their anticancer activity. Considering the critical role of HMGB1 in the cell cycle, we analyzed cell cycle response to active GMMs in CRC cells in a Muse flow cell analyzer. Docking studies were further performed to predict the binding modes and affinity of active GMM for HMGB1. A total of thirteen GMMs were synthesized and their anticancer activity was evaluated on each of the SW480, HT29 and DLD1 CRC cell lines. Of the 13\u2010novel synthetic GMMs assessed,\n                    <jats:bold>A1<\/jats:bold>\n                    ,\n                    <jats:bold>A2<\/jats:bold>\n                    ,\n                    <jats:bold>A3<\/jats:bold>\n                    and\n                    <jats:bold>A6<\/jats:bold>\n                    were found to be the most active, with anticancer inhibitory concentrations (IC80) of 250\u2013500\u03bcg\/mL. Treatment with active GMM\u2032s resulted in CRC cells being arrested mainly in preparatory phases of the cell cycle. Docking studies established that the active GMMs possessed specific binding affinity with the target, compared to the inactive GMM.\n                  <\/jats:p>","DOI":"10.1002\/slct.201800629","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T14:52:53Z","timestamp":1530024773000},"page":"6942-6948","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anticancer Activity of Novel Gabexate Mesilate Mimetics in Colorectal Cancer Cells"],"prefix":"10.1002","volume":"3","author":[{"given":"Amber","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Faculty of Health Sciences University of the Witwatersrand  7 York Road, Parktown Johannesburg 2193 South Africa"}]},{"given":"Mohmmad Younus","family":"Wani","sequence":"additional","affiliation":[{"name":"Chemistry Department Faculty of Science University of Jeddah, P.O. Box 80327  Jeddah 21589 Kingdom of Saudi Arabia"}]},{"given":"Abdullah Saad","family":"Al\u2010Bogami","sequence":"additional","affiliation":[{"name":"Chemistry Department Faculty of Science University of Jeddah, P.O. Box 80327  Jeddah 21589 Kingdom of Saudi Arabia"}]},{"given":"Kumar","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Health Sciences University of the Witwatersrand  7 York Road, Parktown Johannesburg 2193 South Africa"}]},{"given":"Jeyalakshmi","family":"Kandhavelu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Health Sciences University of the Witwatersrand  7 York Road, Parktown Johannesburg 2193 South Africa"}]},{"given":"Paul","family":"Ruff","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Health Sciences University of the Witwatersrand  7 York Road, Parktown Johannesburg 2193 South Africa"}]},{"given":"Clement","family":"Penny","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Health Sciences University of the Witwatersrand  7 York Road, Parktown Johannesburg 2193 South Africa"}]}],"member":"311","published-online":{"date-parts":[[2018,6,26]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(85)90539-7"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2015.00087"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0490"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.114.091850"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4958"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.32184"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13084"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2793"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21262"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-015-0166-1"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034318"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.19891"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2015.1017691"},{"key":"e_1_2_6_14_1","first-page":"5268","volume":"21","author":"Guglielmi V.","year":"2017","journal-title":"Eur. 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