THE INHIBITORY EFFECT OF METHANOLIC AND AQUEOUS EXTRACTS OF TERMINALIA CHEBULA DRIED FRUITS ON METALLOBETALACTAMASES OF ACINETOBACTER BAUMANNII

Objective: toevaluate Metallo-betalactamase (MBL) inhibitory effect and antimicrobial activity against Acinetobacter baumannii of methanolic and aqueous extracts of Terminaliachebuladried fruits.Methods: effect of EDTA (Ethylenediaminetetraacetic acid), methanolic and aqueous extracts of dried fruits of T. chebula on Metallo-betalactamase activity was studied in vitroby using cephaloridin asasubstrate. The degree of inhibition was determined byIC50and the antimicrobial activities of both extracts against Acinetobacter baumannii were qualitatively and quantitatively assessed by the presence or absence of inhibition zones, MIC and MBC values.Results: EDTA, methanolic and aqueous extracts inhibit metallo-betalactamases activity withIC50(3.98 mM, 18.45 and 19.68µg/ml), respectively. Polyphenols in aqueousand methanolic extracts are 513.094±3.061 and 496±2.856 µg GAE/mg, respectively.Conclusion: These results indicate that both extracts of T. chebula are rich in polyphenols and have a strong inhibitory effect on metallo-betalactamases in a competitive manner compared to EDTA. In addition, both extracts of T. chebula were also screened for their remarkable antibacterial and bactericidal activity against Acinetobacter baumannii confirmed by low minimum inhibitory and bactericidal concentration (MIC and MBC).Â

Synthesis, crystal structure, quantum chemical calculations, electrochemistry and electro-catalytical properties as cytochrome P-450 model of tetradentate Mn(III)-Schiff base complex.

339-353The tetradentate Schiff base ligand has been obtained from condensation with mixing ethylenediamine and 2 mmoles of 5-methoxy-2-hydroxybenzaldehyde in absolute ethanol H2L. To the ethanolic solution was added manganese(II)acetatetetrahydrated and lithium chloride (LiCl) to obtain the tetradentate manganese(III) Schiff base complex [Mn(III)(Cl)L]. Theprepared compounds have been characterized by several spectroscopic techniques such as elemental analyses, FT-IR, UV–vis., 1H NMR and HRMS. In this paper, the X-ray diffraction (XRD) and the computational studies (DFT) of the ligand(H2L) with its manganese(III)-Schiff base complex [Mn(III)(Cl)L] are described and confirmed the given molecularstructures. The crystallographic studies have been utilized toelucidate the kinetics, selectivity and stereochemistry of thetransferred oxygen atomsto the substrate molecules when the considered complex is used as catalyst accordingthecytochrome P450 model. In addition, the density functional theory (DFT) calculation with B3LYP/6-31G(d,p) level isperformed to obtain the optimized geometries and electronic properties of the prepared compounds. The global reactivityparameters have also been calculated using the energies of frontier molecular orbitals suggesting that the ligand H2L is morestable than its Mn(III) complex. This may be due to the presence of hydrogen bonds in the ligand and the weaker energies ofcoordination bonds in the complex. The electrochemical behaviour of Mn(III)(Cl)L has been studied by cyclic voltammetryin acetonitrile solutions at room temperature. The resulting cyclic voltammogram shows Mn(III)/Mn(II) couple at E1/2= -0.62V with glassy carbon (GC) electrode. This redox couple is involved in the electrocatalytic cycle where themanganese(III) cation is successively mono-electronated until the formation of superoxo intermediates and then the oxospecies, respectively. These oxo forms, generated in situ, transfer their oxygen atoms to the substrate giving the oxidizedproduct. So, the chemical and electrochemical reactions, implicated in this electrocatalytical process, obey to the biomimeticoxidation reactions as those of monooxygenase enzymes (Cytochrome P450)

Design, structural and theoretical characterizations of novel Schiff base compounds: Enzymes inhibitory potential using in vitro and in silico methods

105-124The aim of this paper is to further explore the enzymatic properties of two synthetic Schiff base compounds. The corresponding copper complex (CuII(L)2), with its Schiff base ligand (HL) have been synthesized and their spectroscopic (IR, UV-visible., NMR (1H, 13C, Dept-135) and MS), thermogravimetric (TG/DTG), electrochemical (CV) and theoretical (Density Functional Theory) using the hybrid B3LYP/6–31 G(d,p) method) properties have been studied and well discussed. The electrochemical behaviour of CuII(L)2 displays the Cu(III)/Cu(II) and Cu(lI)/Cu(I) redox processes. The molecular structure of HL is confirmed by X-ray diffraction analysis. HL crystalized in the triclinic system with the space group of P-1. The morphological structures are also analyzed by X-ray powder diffraction, scanning electron microscopy with energy-dispersive X-ray spectroscopy. To improve their biological activities, inhibition of the target proteins, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), Tyrosinase (TYR), and Urease enzymes are tested in vitro and in silico using molecular docking. Furthermore, their ADMET parameters are analyzed. The drug-likeness results indicate that HL followed to Lipinski’s, Ghose’s, Veber’s, Egan’s and Muegge’s rules contrary to its copper complex which followed only to Veber’s rule. Due to the importance of cytochrome P450s proteins for detoxification, five major CYP isoforms (CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4) are also considered during in silico prediction