{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:25Z","timestamp":1787029105182,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008856","name":"Department of Health of Zhejiang Province","doi-asserted-by":"publisher","award":["11-CX29"],"award-info":[{"award-number":["11-CX29"]}],"id":[{"id":"10.13039\/501100008856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Bisphenol A (BPA) analogues substituted on the benzene ring are widely used in a variety of industrial and consumer materials. However, their effects on the glucocorticoid-metabolizing enzyme 11\u03b2-hydroxysteroid dehydrogenase 1 (11\u03b2-HSD1) remain unclear. The inhibitory effects of 6 BPA analogues on the inhibition of human and rat 11\u03b2-HSD1 were investigated. The potencies of inhibition on human 11\u03b2-HSD1 were bisphenol H (IC50, 0.75 \u00b5M) &gt; bisphenol G (IC50, 5.06 \u00b5M) &gt; diallyl bisphenol A (IC50, 13.36 \u00b5M) &gt; dimethyl bisphenol A (IC50, 30.18 \u00b5M) &gt; bisphenol A dimethyl ether (IC50, 33.08 \u00b5M) &gt; tetramethyl bisphenol A (&gt;100 \u00b5M). The inhibitory strength of these chemicals on rat 11\u03b2-HSD1 was much weaker than that on the human enzyme, ranging from 74.22 to 205.7 \u00b5M. All BPA analogues are mixed\/competitive inhibitors of both human and rat enzymes. Molecular docking studies predict that bisphenol H and bisphenol G both bind to the active site of human 11\u03b2-HSD1, forming a hydrogen bond with catalytic residue Ser170. The bivariate correlation of IC50 values with LogP (lipophilicity), molecular weight, heavy atoms, and molecular volume revealed a significant inverse regression and the correlation of IC50 values with \u0394G (low binding energy) revealed a positive regression. In conclusion, the lipophilicity, molecular weight, heavy atoms, molecular volume, and binding affinity of a BPA analogue determine the inhibitory strength of human and rat 11\u03b2-HSD isoforms.<\/jats:p>","DOI":"10.3390\/molecules28134894","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T02:09:17Z","timestamp":1687399757000},"page":"4894","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bisphenol A Analogues Inhibit Human and Rat 11\u03b2-Hydroxysteroid Dehydrogenase 1 Depending on Its Lipophilicity"],"prefix":"10.3390","volume":"28","author":[{"given":"Hong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou 325027, China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Structural Malformations in Children of Zhejiang Province and Key Laboratory of Male Health and Environment of Wenzhou, Wenzhou 325000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou 325027, China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyao","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou 325027, China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou 325027, China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou 325027, China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huitao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou 325027, China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou 325027, China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou 325027, China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renshan","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou 325027, China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325027, China"},{"name":"Key Laboratory of Structural Malformations in Children of Zhejiang Province and Key Laboratory of Male Health and Environment of Wenzhou, Wenzhou 325000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3389\/fendo.2020.00447","article-title":"Bisphenols and Leydig Cell Development and Function","volume":"11","author":"Li","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e12730","DOI":"10.1111\/jne.12730","article-title":"Achieving CLARITY on bisphenol A, brain and behaviour","volume":"32","author":"Patisaul","year":"2020","journal-title":"J. Neuroendocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3803\/EnM.2019.34.4.340","article-title":"Bisphenols and Thyroid Hormone","volume":"34","author":"Kim","year":"2019","journal-title":"Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kim, J.J., Kumar, S., Kumar, V., Lee, Y.M., Kim, Y.S., and Kumar, V. (2019). Bisphenols as a Legacy Pollutant, and Their Effects on Organ Vulnerability. Int. J. Environ. Res. Public Health, 17.","DOI":"10.20944\/preprints201912.0241.v1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.2174\/1570159X17666190726112101","article-title":"Neuro-toxic and Reproductive Effects of BPA","volume":"17","author":"Santoro","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108575","DOI":"10.1016\/j.envres.2019.108575","article-title":"The adverse health effects of bisphenol A and related toxicity mechanisms","volume":"176","author":"Ma","year":"2019","journal-title":"Environ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dallio, M., Diano, N., Masarone, M., Gravina, A.G., Patane, V., Romeo, M., Di Sarno, R., Errico, S., Nicolucci, C., and Abenavoli, L. (2019). Chemical Effect of Bisphenol A on Non-Alcoholic Fatty Liver Disease. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16173134"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.scitotenv.2017.10.252","article-title":"The occurrence and source identification of bisphenol compounds in wastewaters","volume":"616\u2013617","author":"Cesen","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.toxlet.2022.07.004","article-title":"Dimethylbisphenol A inhibits the differentiation of stem Leydig cells in adult male rats by androgen receptor (NR3C4) antagonism","volume":"366","author":"Shi","year":"2022","journal-title":"Toxicol. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.scitotenv.2018.08.047","article-title":"Mass flows and removal of eight bisphenol analogs, bisphenol A diglycidyl ether and its derivatives in two wastewater treatment plants in New York State, USA","volume":"648","author":"Xue","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.tox.2019.04.003","article-title":"Functional profiling of bisphenols for nuclear receptors","volume":"420","author":"Grimaldi","year":"2019","journal-title":"Toxicology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1177\/0960327110372400","article-title":"Development of molecular docking-based binding energy to predict the joint effect of BPA and its analogs","volume":"30","author":"Zhang","year":"2011","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1037\/a0034186","article-title":"Early environments, glucocorticoid receptors, and behavioral epigenetics","volume":"127","author":"Champagne","year":"2013","journal-title":"Behav. Neurosci."},{"key":"ref_14","first-page":"219","article-title":"Inhibitory effects of some possible endocrine-disrupting chemicals on the isozymes of human 11beta-hydroxysteroid dehydrogenase and expression of their mRNA in gonads and adrenal glands","volume":"12","author":"Ohshima","year":"2005","journal-title":"Environ. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/asia.201301428","article-title":"11beta-hydroxysteroid dehydrogenase types 1 and 2 in postnatal development of rat testis: Gene expression, localization and regulation by luteinizing hormone and androgens","volume":"16","author":"Zhou","year":"2014","journal-title":"Asian J. Androl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1152\/physrev.00020.2012","article-title":"11beta-hydroxysteroid dehydrogenases: Intracellular gate-keepers of tissue glucocorticoid action","volume":"93","author":"Chapman","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.toxlet.2012.10.002","article-title":"Inhibition of human and rat 11beta-hydroxysteroid dehydrogenases activities by bisphenol A","volume":"215","author":"Guo","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1210\/en.2005-0117","article-title":"Minireview: Hexose-6-phosphate dehydrogenase and redox control of 11{beta}-hydroxysteroid dehydrogenase type 1 activity","volume":"146","author":"Hewitt","year":"2005","journal-title":"Endocrinology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16653","DOI":"10.1016\/S0021-9258(18)55351-5","article-title":"The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization","volume":"266","author":"Tannin","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1210\/endo.138.6.5165","article-title":"Identification of a kinetically distinct activity of 11beta-hydroxysteroid dehydrogenase in rat Leydig cells","volume":"138","author":"Ge","year":"1997","journal-title":"Endocrinology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1677\/jme.1.01736","article-title":"Comparative enzymology of 11beta-hydroxysteroid dehydrogenase type 1 from six species","volume":"35","author":"Arampatzis","year":"2005","journal-title":"J. Mol. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/0006-291X(92)92373-6","article-title":"Tyr-179 and Lys-183 are essential for enzymatic activity of 11 beta-hydroxysteroid dehydrogenase","volume":"188","author":"Obeid","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113739","DOI":"10.1016\/j.fct.2023.113739","article-title":"Halogen atoms determine the inhibitory potency of halogenated bisphenol A derivatives on human and rat placental 11beta-hydroxysteroid dehydrogenase 2","volume":"175","author":"Shi","year":"2023","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"114715","DOI":"10.1016\/j.ecoenv.2023.114715","article-title":"Direct inhibition of bisphenols on human and rat 11beta-hydroxysteroid dehydrogenase 2: Structure-activity relationship and docking analysis","volume":"254","author":"Zhang","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110243","DOI":"10.1016\/j.cbi.2022.110243","article-title":"Chemicals of environmental concern as inhibitors of human placental 3beta-hydroxysteroid dehydrogenase 1 and aromatase: Screening and docking analysis","volume":"368","author":"Tang","year":"2022","journal-title":"Chem. Biol. Interact."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.toxlet.2011.09.001","article-title":"Inhibition of human and rat testicular steroidogenic enzyme activities by bisphenol A","volume":"207","author":"Ye","year":"2011","journal-title":"Toxicol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"153334","DOI":"10.1016\/j.tox.2022.153334","article-title":"Structure-activity relationship analysis of perfluoroalkyl carbonic acids on human and rat placental 3beta-hydroxysteroid dehydrogenase activity","volume":"480","author":"Wang","year":"2022","journal-title":"Toxicology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"765251","DOI":"10.3389\/fendo.2021.765251","article-title":"Effects of Midazolam on the Development of Adult Leydig Cells from Stem Cells In Vitro","volume":"12","author":"Zhao","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1021\/jm4016729","article-title":"Optimization of brain penetrant 11beta-hydroxysteroid dehydrogenase type I inhibitors and in vivo testing in diet-induced obese mice","volume":"57","author":"Goldberg","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6948","DOI":"10.1021\/bi047599q","article-title":"Crystal structure of murine 11 beta-hydroxysteroid dehydrogenase 1: An important therapeutic target for diabetes","volume":"44","author":"Zhang","year":"2005","journal-title":"Biochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold protein structure database: Massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"103389","DOI":"10.1016\/j.sjbs.2022.103389","article-title":"In silico investigation of ACE2 and the main protease of SARS-CoV-2 with phytochemicals from Myristica fragrans (Houtt.) for the discovery of a novel COVID-19 drug","volume":"29","author":"Ongtanasup","year":"2022","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ongtanasup, T., Mazumder, A., Dwivedi, A., and Eawsakul, K. (2022). Homology Modeling, Molecular Docking, Molecular Dynamic Simulation, and Drug-Likeness of the Modified Alpha-Mangostin against the beta-Tubulin Protein of Acanthamoeba Keratitis. Molecules, 27.","DOI":"10.3390\/molecules27196338"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"W611","DOI":"10.1093\/nar\/gkac305","article-title":"ProteinsPlus: A comprehensive collection of web-based molecular modeling tools","volume":"50","author":"Diedrich","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"42795","DOI":"10.1074\/jbc.M208537200","article-title":"Structure\/function relationships responsible for the kinetic differences between human type 1 and type 2 3beta-hydroxysteroid dehydrogenase and for the catalysis of the type 1 activity","volume":"277","author":"Thomas","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/protein\/8.2.127","article-title":"LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions","volume":"8","author":"Wallace","year":"1995","journal-title":"Protein Eng."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10652","DOI":"10.1021\/jm3013163","article-title":"Free-Wilson and structural approaches to co-optimizing human and rodent isoform potency for 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors","volume":"55","author":"Goldberg","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1021\/ci049714+","article-title":"ZINC\u2014A free database of commercially available compounds for virtual screening","volume":"45","author":"Irwin","year":"2005","journal-title":"J. Chem. Inf. Model."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/4894\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:57:53Z","timestamp":1760126273000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/4894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":39,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["molecules28134894"],"URL":"https:\/\/doi.org\/10.3390\/molecules28134894","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,21]]}}}