title: Synthesis, functionalization and biological activity of arylated derivatives of (+)-estrone.
abstract: Various novel arylated estrone derivatives, such as 2-aryl-, 4-aryl- and 2,4-diaryl-estrones, by Suzuki-Miyaura reactions. While the synthesis of 4-arylestrones could be carried out under standard conditions, the synthesis of 2-arylestrones and 2,4-diarylestrones required a thorough optimization of the conditions and it proved to be important to use sterically encumbered biaryl ligands. The best results were obtained by the use of RuPhos. Combination of developed Suzuki coupling reactions with subsequent cyclization reactions afforded more complex hybrid structures, containing dibenzofuran, benzocoumarin and steroid moieties. These derivatives were tested as pancreatic lipase inhibitors and it was found that most of the compounds exhibited inhibition of pancreatic lipase but the maximum inhibitory potential was shown by 4-arylestrones. All of the synthesized derivatives showed inhibitory values in the range of 0.82±0.01-59.7±3.12μM. The biological activity was also rationalized on the bases of docking studies.
authors.affiliation: Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Ivanov
authors.affiliation: Center for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Syeda Abida
authors.initials: SA
authors.lastname: Ejaz
authors.affiliation: Center for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Syed Jawad Ali
authors.initials: SJA
authors.lastname: Shah
authors.affiliation: Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany; Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ehlers
authors.affiliation: Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Villinger
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Frank
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Schneider
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
authors.affiliation: Amity University, Lucknow Campus, Viraj Khand-5, Gomti Nagar, Lucknow 226010, India.
authors.forename: Qamar
authors.initials: Q
authors.lastname: Rahman
authors.affiliation: Center for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany; Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany. Electronic address: peter.langer@uni-rostock.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Langer
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004970:Estrone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D010179:Pancreas / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D004970:Estrone; D008049:Lipase
keywords: Catalysis; Phosphatase inhibition; Steroids; Suzuki reaction