{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:00:49Z","timestamp":1788544849858,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The primary strategy in the fight against cancer is to screen compounds that may be effective on different types of cancer. Compounds from plants seem to be a good source. The present study investigated the inhibitory effects of some flavonoids on the 6\u2010phosphogluconate dehydrogenase (6\u2010PGD) enzyme. We determined that quercetin, myricetin, fisetin, morin, apigenin, and baicalein exhibited powerful inhibition effects with IC<jats:sub>50<\/jats:sub> values between 4.08 and 21.26\u2009\u00b5M, while luteolin, kaempferol, apiin, galangin, and baicalin showed moderate effects with IC<jats:sub>50<\/jats:sub> values between 54.15 and 138.91\u2009\u00b5M. Quercetin competitively inhibited the binding of NADP and 6\u2010phosphogluconate to the 6\u2010PGD enzyme with <jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> values of 0.527\u2009\u00b1\u20090.251 and 0.374\u2009\u00b1\u20090.138\u2009\u00b5M, respectively. We calculated <jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> values using the Cheng\u2013Prusoff equation as between 0.44 and 14.88\u2009\u00b5M. The possible interaction details of polyphenols with the active site of 6\u2010PGD were analyzed with docking software. In silico and in vitro studies indicated that the \u2013OH groups on the A and C ring of flavonoids bind to the enzyme's active site via hydrogen bonding, while the \u2013OH groups on the C ring contributed significantly to the increase in the inhibitory potentials of the molecules. Molecular dynamic simulations tested the stability of the 6\u2010PGD\u2010quercetin complex during 100\u2009ns. These phytochemicals were suitable for drug use when optimized with absorption, distribution, metabolism, excretion, and toxicity (ADMET) criteria. The effects of the studied compounds on cancer cell lines of potential targets were demonstrated by network analysis. In conclusion, this study suggests that flavonoids found to be potent inhibitors could serve as leading candidates to treat many cancers via 6\u2010PGD inhibition.<\/jats:p>","DOI":"10.1002\/ardp.202300326","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T11:04:36Z","timestamp":1699355076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Natural flavonoids as promising 6\u2010phosphogluconate dehydrogenase inhibitor candidates: In silico and in vitro assessments"],"prefix":"10.1002","volume":"357","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2146-5870","authenticated-orcid":false,"given":"\u015eevki","family":"Adem","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences \u00c7ank\u0131r\u0131 Karatekin University  \u00c7ank\u0131r\u0131 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00dcmit","family":"Y\u0131rt\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Kirikkale University  Kirikkale Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mesut","family":"Ayd\u0131n","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences \u00c7ank\u0131r\u0131 Karatekin University  \u00c7ank\u0131r\u0131 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-1046","authenticated-orcid":false,"given":"Ravi","family":"Rawat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Health Sciences and Technology UPES University  Dehradun India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volkan","family":"Ey\u00fcpo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences \u00c7ank\u0131r\u0131 Karatekin University  \u00c7ank\u0131r\u0131 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"49","volume-title":"Cancer: The Enemy from Within: A Comprehensive Textbook of Cancer's Causes, Complexities and Consequences","author":"Compton C.","year":"2020"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.039"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81683-9"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.06.001"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2017.179"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.05.006"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10020085"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22193"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570179413666160929142724"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21592"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3255"},{"key":"e_1_2_6_13_1","volume-title":"Phytochemicals as Lead Compounds for New Drug Discovery","author":"Egbuna C.","year":"2019"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu2121231"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.10.004"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.podrm.2020.07.005"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4683"},{"key":"e_1_2_6_18_1","first-page":"11","volume":"2","author":"Anthony D.","year":"2001","journal-title":"Drug Discov."},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.01127.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.37349\/etat.2020.00018"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00066-6"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2021.1951756"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab255"},{"key":"e_1_2_6_24_1","first-page":"59","volume-title":"Advances in Biochemical Engineering\/Biotechnology","author":"Sen T.","year":"2015"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1047"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756360903257900"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm051197e"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.12.043"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2019.1700165"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.11.001"},{"key":"e_1_2_6_33_1","first-page":"252","volume-title":"Gromacs\u2010a parallel computer for molecular\u2010dynamics simulations, 4th International Conference on Computational Physics (PC 92)","author":"Bekker H.","year":"1993"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00249-011-0700-9"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00355047"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp003020w"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/08927028808080941"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-4655(95)00042-E"},{"key":"e_1_2_6_39_1","author":"Hess B.","year":"1977","journal-title":"Comput. Chem."},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00648"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2020-0191"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1784288"},{"key":"e_1_2_6_44_1","first-page":"7","volume":"1996","author":"Vaught A.","year":"1996","journal-title":"Linux J."},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202300326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T04:52:53Z","timestamp":1705726373000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202300326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,7]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/ardp.202300326"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202300326","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,7]]},"assertion":[{"value":"2023-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2300326"}}