title: Insight into inhibition of the human amyloid beta protein precursor (APP: PDB ID ) using (E)-N-(pyridin-2-ylmethylene)arylamine (LR) models: structure elucidation of a family of ZnX2-LR complexes.
abstract: The amyloid beta precursor protein (APP) and its neurotoxic cleavage product amyloid beta (Aβ) are a cause of Alzheimer's disease and appear essential for neuronal development and cell homeostasis. Proteolytic processing of APP is influenced by metal ions and protein ligands, however the structural and functional mechanism of APP regulation is not known so far. In this context, molecular modeling studies were performed to understand the molecular behavior of (E)-N-(pyridin-2-ylmethylene)arylamines (LR) with an E2 domain of the APP in its complex with zinc (APP; PDB ID: ). Docking results indeed confirmed that the LR interacts with Zn in the binding site of the protein between two α-helical chains. In view of these findings, LR was further investigated for complexation reactions with Zn(2+) in order to establish the structural models in solution and in the solid state. Five new Zn(2+) complexes of compositions viz. [Zn(Br)2(L2-Me)] (), [Zn(Br)2(L2-OMe)] (), [Zn(i)2(L2-OMe)] (), [Zn(NO3)2(L2-OMe)(H2O)] () and [Zn(L4-Me)2(H2O)2](NO3)2 () were synthesized and their structures were ascertained by microanalysis, IR and (1)H NMR spectroscopy, and single-crystal X-ray diffraction. The zinc atom in complex exhibits a distorted tetrahedral geometry while the crystal structures of complexes and show distorted square pyramidal geometries. The zinc cation in and has an octahedral coordination environment, but in the zinc coordination geometry is less distorted. The Zn(ii) cations take part in one ( and ) or two () 5-membered metallacycles imposed by the NN or NNO chelation modes of LR. The significant intermolecular ππ interactions are also discussed.
authors.affiliation: Centre for Advanced Studies in Chemistry, North-Eastern Hill University, NEHU Permanent Campus, Umshing, Shillong 793 022, India. basubaul@nehu.ac.in basubaulchem@gmail.com.
authors.forename: Tushar S
authors.initials: TS
authors.lastname: Basu Baul
authors.forename: Sajal
authors.initials: S
authors.lastname: Kundu
authors.forename: Palwinder
authors.initials: P
authors.lastname: Singh
authors.lastname: Shaveta
authors.forename: M Fátima C
authors.initials: MF
authors.lastname: Guedes da Silva
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D011725:Pyridines / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D016564:Amyloid beta-Protein Precursor; D008024:Ligands; D009942:Organometallic Compounds; D011725:Pyridines; D015032:Zinc; C023666:pyridine