20.500.12556/DKUM-92466 Inverse molecular docking elucidating the anticarcinogenic potential of the hop natural product xanthohumol and its metabolites Natural products from plants exert a promising potential to act as antioxidants, antimicrobials, anti-inflammatory, and anticarcinogenic agents. Xanthohumol, a natural compound from hops, is indeed known for its anticarcinogenic properties. Xanthohumol is converted into three metabolites: isoxanthohumol (non-enzymatically) as well as 8- and 6-prenylnaringenin (enzymatically). An inverse molecular docking approach was applied to xanthohumol and its three metabolites to discern their potential protein targets. The aim of our study was to disclose the potential protein targets of xanthohumol and its metabolites in order to expound on the potential anticarcinogenic mechanisms of xanthohumol based on the found target proteins. The investigated compounds were docked into the predicted binding sites of all human protein structures from the Protein Data Bank, and the best docking poses were examined. Top scoring human protein targets with successfully docked compounds were identified, and their experimental connection with the anticarcinogenic function or cancer was investigated. The obtained results were carefully checked against the existing experimental findings from the scientific literature as well as further validated using retrospective metrics. More than half of the human protein targets of xanthohumol with the highest docking scores have already been connected with the anticarcinogenic function, and four of them (including two important representatives of the matrix metalloproteinase family, MMP-2 and MMP-9) also have a known experimental correlation with xanthohumol. Another important protein target is acyl-protein thioesterase 2, to which xanthohumol, isoxanthohumol, and 6-prenylnaringenin were successfully docked with the lowest docking scores. Moreover, the results for the metabolites show that their most promising protein targets are connected with the anticarcinogenic function as well. We firmly believe that our study can help to elucidate the anticarcinogenic mechanisms of xanthohumol and its metabolites as after consumption, all four compounds can be simultaneously present in the organism. xanthohumol metabolites inverse molecular docking anticarcinogenic effects ksantohumol metaboliti antirarakatvorni učinki true false true MDPI AG Angleški jezik Slovenski jezik https://www.mdpi.com/journal/foods © 2022 by the authors Članek v reviji 2025-04-10 13:47:17 2025-04-10 13:47:17 2025-04-11 03:14:11 0000-00-00 00:00:00 2022 0 0 17 str. iss. 9 Vol. 11 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2022-03-29 2022-04-25 2022-04-26 577 106275075 10.3390/foods11091253 2304-8158 foods-11-01253-v2.pdf foods-11-01253-v2.pdf 1 A68A4864C57AB64F685041A508610FF3 09fb32f218510a18c52f8a250e862a518ad9f906456a43ba955b51b92097e42f 4f75ee70-1602-11f0-980a-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=190193 https://www.mdpi.com/2304-8158/11/9/1253 0 53fce6a8-1602-11f0-980a-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=190194 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0