title: Synthesis, alkaline phosphatase inhibition studies and molecular docking of novel derivatives of 4-quinolones.
abstract: New and convenient methods for the functionalization of the 4-quinolone scaffold at positions C-1, C-3 and C-6 were developed. The 4-quinolone derivatives were evaluated for their inhibitory potential on alkaline phosphatase isozymes. Most of the compounds exhibit excellent inhibitory activity and moderate selectivity. The IC50values on tissue non-specific alkaline phosphatase (TNAP) were in the range of 1.34 ± 0.11 to 44.80 ± 2.34 μM, while the values on intestinal alkaline phosphatase (IAP) were in the range of 1.06 ± 0.32 to 192.10 ± 3.78 μM. The most active derivative exhibits a potent inhibition on IAP with a ≈14 fold higher selectivity as compared to TNAP. Furthermore, molecular docking calculations were performed for the most potent inhibitors to show their binding interactions within the active site of the respective enzymes.
authors.affiliation: Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany.
authors.forename: Mariia
authors.initials: M
authors.lastname: Miliutina
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
authors.forename: Syeda Abida
authors.initials: SA
authors.lastname: Ejaz
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
authors.forename: Shafi Ullah
authors.initials: SU
authors.lastname: Khan
authors.affiliation: Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany; National Taras Shevchenko University, 62 Volodymyrska Str., 01033 Kyiv, Ukraine. Electronic address: iva108@googlemail.com.
authors.forename: Viktor O
authors.initials: VO
authors.lastname: Iaroshenko
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: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, 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: D042462:4-Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
chemical_list: D042462:4-Quinolones; D004791:Enzyme Inhibitors; D000469:Alkaline Phosphatase
keywords: Alkaline phosphatase; Aminoheterocycles; Bromination; Molecular docking calculations; Quinolones; Sonogashira reaction; Trifluoromethylation