title: Synthesis, docking study and β-adrenoceptor activity of some new oxime ether derivatives.
abstract: A new series of oxime ethers 4a-z was designed and synthesized to test the blocking activity against β₁ and β₂-adrenergic receptors. Docking of these ether derivatives into the active site of the identified 3D structures of β₁ and β₂-adrenergic receptors showed MolDock scores comparable to those of reference compounds. Biological results revealed that the inhibition effects on the heart rate and contractility are less than those of propranolol. Nevertheless, the two compounds 4p and 4q that displayed the highest negative MolDock score with β₂-adrenergic receptors showed β₂-antagonistic activity by decreasing salbutamol relaxation of precontracted tracheal strips, which indicates the importance of a chlorothiophene moiety in the hydrophobic region for best complementarity with β₂ receptors. On other hand, the presence of a homoveratryl moiety increases the MolDock score of the tested compounds with the β₁ receptor.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. hghabbour@mans.edu.eg.
authors.forename: Hazem A
authors.initials: HA
authors.lastname: Ghabbour
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Eman R
authors.initials: ER
authors.lastname: El-Bendary
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Mahmoud B
authors.initials: MB
authors.lastname: El-Ashmawy
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: El-Kerdawy
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D010091:Oximes / Q000737:chemistry*; D011943:Receptors, Adrenergic, beta / Q000737:chemistry* / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D004987:Ethers; D010091:Oximes; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2