Search

Ebola virus (EBOV) causes zoonotic viral infection with a potential risk of global spread and a highly fatal effect on humans. Till date, no drug has gotten market approval for the treatment of Ebola virus disease (EVD), and this perhaps allows the use of both experimental and computational approaches in the antiviral drug discovery process. The main target of potential vaccines that are recently undergoing clinical trials is trimeric glycoprotein (GP) of the EBOV and its exact crystal structure was used in this structure based virtual screening study, with the aid of consensus scoring to select three possible hit compounds from about 36 million compounds in MCULE’s database. Amongst these three compounds, (5R)-5-[[5-(4-chlorophenyl)-1,2,4-oxadiazol-3-yl]methyl]-N-[(4-methoxyphenyl)methyl]-4,5-dihydroisoxazole-3-carboxamide (SC-2, C 21 H 19 ClN 4 O 4 ) showed good features with respect to drug likeness, ligand efficiency metrics, solubility, absorption and distribution properties and non-carcinogenicity to emerge as the most promising compound that can be optimized to lead compound against the GP EBOV. The binding mode showed that SC-2 is well embedded within the trimeric chains of the GP EBOV with molecular interactions with some amino acids. The SC-2 hit compound, upon its optimization to lead, might be a good potential candidate with efficacy against the EBOV pathogen and subsequently receive necessary approval to be used as antiviral drug for the treatment of EVD. [ABSTRACT FROM AUTHOR]

Five new gold(I) complexes of carbene and selenone ligands ( 1 – 5 ) having the general formula, [Au(IPr)(selenone)]PF 6 were synthesized by the reaction of [Au(IPr)Cl] ( 0 ) with selenones (IPr = 1,3-Bis(2,6-di-isopropylphenyl)imidazol-2-ylidene and selenone = 1,3-imidazolidine-2-selenone, N- ethyl-1,3-imidazolidine-2-selenone, N -propyl-1,3-imidazolidine-2-selenone, N,N′ -dimethyl-1,3-imidazolidine-2-selenone and N,N′ -diethyl-1,3-imidiazolidine-2-selenone for 1 – 5 respectively). The complexes were characterized by elemental analysis, IR and NMR ( 1 H, 13 C, 77 Se) spectroscopy, and two of them by X-ray crystallography. The X-ray diffraction analysis of complexes 2 and 4 revealed that they were composed of [Au(IPr)(Selenone)] + and PF 6 − ions. In the complex ions, gold(I) atom adopts a linear geometry. In vitro cytotoxicity was appraised for all complexes against HCT15, A549 and MCF7 cancer cell lines. The IC 50 values showed that the complexes exhibited poor activity as compared to cisplatin. However, the complex 1 showed a promising anticancer activity (IC 50 = 33 ± 1 μM) similar to that exhibited by cisplatin (32 ± 2 μM) against HCT15 (human colon cancer) cell line. The molecular docking analysis showed the potential inhibitory capacity of the gold complexes with thioredoxin reductase with complex 4 having the highest binding affinity with a score of −34.45. The interactions of the gold complexes with tryptophan and lysozyme were studied electrochemically using Cyclic and Square Wave Voltammetry. [ABSTRACT FROM AUTHOR]

The Zika virus (ZIKV) is a life threatening pathogen of zoonotic importance with prevalence in some parts of Africa and America. Unfortunately, there is yet to be a single approved vaccine or antiviral drug to treat the diseases and deformations being caused by the Zika virus infection. In this study, about 36 million compounds from MCULE database were virtually screened against a real matured ZIKV protein using a consensus scoring method to get improved hit rates. The consensus scoring method combined the result from the 25 top ranked molecules from both MCULE and Drug Score eXtended (DSX) docking programs which led to the selection of two hit compounds. The inhibition constant (Ki) values of 0.08 and 0.30 μm were obtained for the two selected compounds MCULE-8830369631-0-1 and MCULE-9236850811-0-1 respectively, to remark them as hit compounds. The molecular interactions of the two selected hit compounds with the amino acids (ALA 48, ILE 49, ILE 468 and LEU 472) present in the ZIKV protein indicated that they both have similar binding modes. The result of the computationally predicted physicochemical properties including ADMET for the selected compounds showed their great potential in becoming lead compounds upon optimization and thus could be used in treating the Zika virus diseases. [ABSTRACT FROM AUTHOR]

The theoretical evaluations of the corrosion inhibition efficiency of 2-(3,4,5-tri-R-benzylidene) hydrazinecarbothioamide, (R = H, CH 3 , OCH 3 and NH 2 ), were done using RHF and DFT-B3LYP methods with 6-31G(d) basis set in gas phase, aqueous and acidic solutions. The correlation between the molecular structures of these compounds and their theoretically predicted inhibition effects was obtained from the quantum chemical evaluations, such that the structural parameters provided insights into the possible inhibition mechanism. 2-(3,4,5-triaminebenzylidene) hydrazinecarbothioamide showed a larger tendency of adsorption through chemisorption and physisorption and thus was identified to be the best potential candidate for excellent corrosion inhibition among the studied compounds. [ABSTRACT FROM AUTHOR]

Gold(I)-carbene complexes containing a selenone ligand (L), [Au(IPr)(L)]PF 6 {where, IPr = 1,3-Bis(2,6-di-isopropylphenyl)imidazol-2-ylidene and L =  N - i -propyl-1,3-imidazolidine-2-selenone, i -PrImSe ( 1 ), 1,3-diazinane-2-selenone, DiazSe ( 2 ), N -methyl-1,3-diazinane-2-selenone, MeDiazSe ( 3 ), 5-hydroxy-1,3-diazinane-2-selenone, HO-DiazSe ( 4 ) and 1,3-diazepane-2-selenone, DiapSe ( 5 )} were synthesized using [Au(IPr)Cl] ( 0 ) and selenones. The complexes ( 1 – 5 ) were characterized by elemental analysis, IR and NMR ( 1 H, 13 C & 77 Se) spectroscopy. The crystal structure of complex 1 was determined by single crystal X-ray diffraction technique and the analysis reveals that the complex exhibits a distorted linear geometry around gold(I) atom. In vitro cytotoxic assays of the complexes were performed on three human cancer cell lines; HCT15 (colon cancer), A549 (lung cancer) and MCF7 (breast adenocarcinoma). Complexes 1 and 3 exhibited greater activities against HCT15 cells compared to the other complexes ( 2 , 4 and 5 ). All complexes exhibited moderate to high IC 50 values (less active) against A549 and MCF7 cell lines with respect to cisplatin. Molecular docking studies showed the potential inhibitory capacity of the gold complexes towards DNA topoisomerase 1 with complex 1 having the highest binding affinity with a score of −38.68. The distance between the gold atom in the complex and the oxygen atom of the carbonyl group of thymine was measured for all complexes. Complex 4 had the shortest bond distance of 3.64 Å, while complex 5 had the longest one of 6.89 Å. [ABSTRACT FROM AUTHOR]

A mutual prodrug (1) of ibuprofen and sulphanilamide has been synthesized with dual activity and improved toxicity profile. The synthesized compound has been characterized by elemental analysis, FT-IR, 1HNMR, 13CNMR and ESI-MS. The molecular geometry of the compound (1) was optimized using density functional theory (DFT/B3LYP) method with the 6-311G(d,p) basis sets in ground state. Geometric parameters (bond lengths, bond angles, torsion angles), vibrational assignments, chemical shifts and thermodynamics of the compound (1) has been calculated theoretically and compared with the experimental data. Comparative AutoDock study of compound (1) with cyclooxygenase enzymes (COX-1 and COX-2) were performed involving docking for possible selectivity of our prodrug within the two Cox enzymes. The highest binding affinities of −8.7 Kcal/mol and −8.1 Kcal/mol has been obtained for COX-1 and COX-2 enzymes respectively. Compound (1) exhibited enhanced anti-inflammatory, anti-ulcer and free radical scavenging activities as compared with the parent drugs. Based on various in vitro and in vivo tests it is suggested that the Compound (1) is more active than the parent drugs. Moreover, LD 50 of compound (1) is higher than parent drug i.e. ibuprofen and sulphanilamide suggesting that the synthesized compound is much safer than its parent analogous. [ABSTRACT FROM AUTHOR]