Xanthine oxidase (XO) catalyses the conversion of hypoxanthine to xanthine and subsequently xanthine to uric acid. The increase of uric acid can lead to gout and other diseases. Allopurinol, an analogue of hypoxanthine, is a specific potent inhibitor and substrate for XO. The most common adverse effects of allopurinol include hypersensitivity reactions, skin rashes, hepatotoxicity and gastrointestinal distress. Thus, there is a need to discover compounds with XO inhibitory activities which devoid of the undesirable effects of allopurinol. It has been shown that flavonoids act as the inhibitors of xanthine oxidase, So quercetin as a flavonoid was chosen and the modes of interaction of quercetin was investigated at the atomic level using in silico means. The aim of this study is to investigate the Inhibitory effect and toxicity of quercetin compared with allopurinol by using molecular modeling techniques. The virtual screening analysis using AutoDock 4.2 and in vitro xanthine oxidase inhibitory activities of allopurinol and quercetin as the substrate were used in this study. In addition, the kinetics of the enzymatic reactions were analyzed using Lineweaver-Burk plot and related to the structural features of the studied inhibitors. The results showed that the inhibitory effect of quercetin is more potent than allopurinol (a standard inhibitor), while showing less toxicity effect.

Objective(s): Recently, phthalimide derivatives were designed based on ameltolide and thalidomide as they possess a similar degree of anticonvulsant potency due to their phenytoin-like profile. The ability of phthalimide pharmacophore to interact with neuronal voltage-dependent sodium channels was studied in the batrachotoxin affinity assay. Therefore, in the present study, a series of 19 compounds of phthalimide pharmacophore possessing a variety of substituents (NO2, NH2, Me, Cl, COOH, MeO) at 2-, 3-, and 4- position of the N-phenyl ring and N- (3-amino-2-methylphenyl) succinimide, were subjected to Docking studies in order to inhibit voltage-gated sodium channels.Materials and Methods: Chemical structures of all compounds were designed using HYPERCHEM program and Conformational studies were performed through semi-empirical molecular orbital calculations method followed by PM3 force field. Total energy gradient calculated as a root mean square (RMS) value, until the RMS gradient was 0.01 kcal mol-1. Among all energy minima conformers, the global minimum of compounds was used in Docking calculations. Using a model of the open pore of Na channels, Docking study was performed by AUTODOCK4.2 program.Results: Docking studies have revealed that these types of ligands interacted mainly with II-S6 residues of NaV1.2 through making hydrogen bonds and have additional hydrophobic interactions with domain I, II, III and IV in the channel's inner pore.Conclusion: These computational studies have displayed that these compounds are capable of inhibiting Na channel, efficiently.

In this work, novel antibacterial drugs that are tetrazole derivatives connected to the 1-position of the heterocyclic ring (benzimidazole) via a methyl bridge were designed and synthesized. The final chemical structures of the prepared tetrazole derivatives were confirmed by nuclear magnetic resonance (1H NMR and 13C NMR), and Fourier-transform infrared spectroscopy (FTIR) spectroscopy. Three types of Candida were used to investigate the synthetic compounds' antifungal properties: Candida albicans, Candida glabrata, and Candida parapsilosis. Compounds e1 and b1 have greater efficacy against Candida albicans than normal fluconazole, while compound d1 shows greater efficacy against Candida glabrata. The ability of compounds to combat gram-positive and gram-negative, Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis was also assessed. The lowest inhibitory concentrations of compounds e1, b1, and c1 against E. faecalis were comparable to those of the control drug azithromycin. Modeling studies were conducted against the 14-α demethylase enzyme found in Candida species. When it came to combating Candida species, e1 was the most effective chemical and had the highest Docking contact energy. Based on the theoretical ADME of prepared compounds calculated, the molecule profiles meet the limitation rule requirements.

The binding interaction of novel podophyllotoxin derivative, (3R, 4R)-4-((benzo[d][1, 3]dioxol-5-yl)methyl)-dihydro-3-(hydroxy(3, 4-dimethoxyphenyl) methyl) furan-2(3H)-one (PPT), with calf thymus DNA (ctDNA) has been examined using UVVisible absorption spectrophotometry, fluorescence spectroscopy, viscosity measurement and molecular Docking studies. UV-Vis absorption results showed hyperchromic effect and low binding constant value (1. 01×104 M-1), indicating nonintercalative interaction as a binding mode. The competitive fluorescence study also confirmed the obtained results from UV-Vis absorption spectra. Small changes in the viscosity of DNA exhibited that the interaction of PPT with DNA is based on groove binding mode. Molecular Docking study showed minor groove interaction and-7. 08 kcal/mol as a calculated energy.

Human serum albumin (HSA) is one of the main endogenous vehicles for biodistribution of molecules by blood plasma. Association equilibrium constants and thermodynamic parameters for the interaction of HSA with Methotrexate were studied by Docking. Docking study provides remarkable information on binding sites of HSA with drugs, estimating the binding parameters in some specific places on biomolecules. Docking study suggests that Methotrexate interacts with one lysine, two arginine, one Asparagine and one Glutamine residues, specifically. The Estimated of Gibbs free energies (Δ G° ) is equal to-52. 67 kJ mol-1 for the best model.