Synthesis, characterization, X-ray, HOMO-LUMO, MEP, FT-IR, NLO, Hirshfeld surface, ADMET, boiled-egg model properties and molecular docking studies with human cyclophilin D (CypD) of a Schiff base compound: (E)-1-(5-nitro-2-(piperidin-1-yl)phenyl)-N-(3-nitrophenyl)methanimine

• Published in: Polyhedron Vol. 205; pp. 115320 - 115329
• Main Authors: Şahin, Songül, Dege, Necmi
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2021; Elsevier
• Subjects: Biological activity; Chemistry; Chemistry, Inorganic & Nuclear; Crystallography; Cyclophilin D; DFT; Molecular docking; Physical Sciences; Schiff base; Science & Technology; Schiff base; Cyclophilin D; DFT; Biological activity; Molecular docking; MITOCHONDRIAL; CRYSTAL-STRUCTURE; RAMAN; P-GLYCOPROTEIN; NMR; CYCLOSPORINE-A; GASTROINTESTINAL ABSORPTION; INHIBITORS; STRESS
• ISSN: 0277-5387; 1873-3719
• DOI: 10.1016/j.poly.2021.115320

[Display omitted] •A Schiff base compound was synthesized and characterized.•NLO, FMOs, MEP, and vibration properties were calculated by DFT method.•Some biological activity parameters (ADMET, BBB penetration, GI absorption, druggability) were determined.•Molecular docking studies were performed on CypD enzyme. The presented study states a new Schiff base compound, (E)-1-(5-nitro-2-(piperidin-1-yl)phenyl)-N-(3-nitrophenyl)methanimine, synthesis and characterization analyses via some computational approaches. On the basis of the X-Ray structure identification method, the structure has the monoclinic crystal system, the P21/n space group, and four molecules in the unit cell (Z). For the title compound, vibrational properties (FTIR), surface analyses (MEP, Hirshfeld), interacting species in secondary interactions (fingerprint plots, dnorm surface, hydrogen bonds), frontier molecular orbitals (FMOs, HOMO-LUMO), and global reactivity descriptors have been calculated and interpreted. The polarizability properties (NLO) of the compound have been determined and compared. With the aim of the determination of bioavailability, some physicochemical and biological parameters included in absorption, distribution, metabolism, excretion (ADME), toxicity, druggability, drug-likeness, blood–brain barrier penetration and gastrointestinal absorption (BOILED-Egg method), drug target identification have been determined and examined via some in silico techniques. A valuable mitochondrial enzyme that was determined in many diseases, CypD, has been chosen as the biological target to be used in molecular docking studies. The inhibition effect of the title compound has been investigated for the CypD enzyme. The docking results show that the compound' inhibition effect on CypD is relatively good. The binding energy of the query molecule has been found −8.06 kcal/mol. However, the compound has positively shown important toxic parameters regarding mutagenicity, hepatotoxic, hERG blockers, drug-induced liver injury. Also, the title compound has been found as an inactive drug candidate for the central nervous system (CNS).