Synthesis, Biological Properties, and Molecular Docking Study of Novel 1,2,3-Triazole-8-quinolinol Hybrids.

A new series of 1,2,3-triazole-8-quinolinol hybrids were synthesized in good yields using monosubstituted acetonitriles and 5-azidomethyl-8-quinolinol as the starting reagents via a one-step protocol. The structures of 1,2,3-triazole-8-quinolinol hybrids were characterized by nuclear magnetic resonance (1H and 13C NMR) spectroscopy and elemental analysis. Antibacterial activity in vitro of all the synthesized hybrids was investigated against Escherichia coli (E. coli), Xanthomonas fragariae (X. fragariae), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis) applying the methods of disk diffusion and minimal inhibition concentration (MIC). Hybrid 7 exhibited excellent antibacterial capacity, with an MIC value of 10 µg/mL against S. aureus and 20 µg/mL against B. subtilis, E. coli, and X. fragariae, which were comparable to those that of the standard antibiotic nitroxoline. A structure-activity relationship (SAR) study of 1,2,3-triazole-8-quinolinol hybrids showed that introducing electron-donating substituents in the 1,2,3-triazole ring at the 4-position is important for activity. Quantum chemical calculations have been undertaken to employ the Gaussian software in the B3LYP, HF, and M062X basis sets using 3-21g, 6-31g, and SDD levels to further explain linkages within the antibacterial findings. Furthermore, molecular docking investigations were also conducted to investigate the binding affinities as well as the interactions of some hybrids with the target proteins. An absorption, distribution, metabolism, excretion, and toxicity (ADME/T) investigation was carried out to scrutinize the viability of employing the 1,2,3-triazole-8-quinolinol hybrids as medicines.

In silico evaluation of molecular interactions between macrocyclic inhibitors with the HCV NS3 protease. Docking and identification of antiviral pharmacophore site.

An array of computational approaches DFT/QSAR/POM methods has been used for a better understanding of drug properties regarding 13 inhibitor derivatives containing either P2 cyclopentane P1 carboxylic acid moiety (1-9) or a P1 cyclopropyl acyl sulfonamide (10-13). To further recognize binding interactions and their activity trends, molecular docking studies were carried out with the use of HCV, which can be used to accurately predict the interactions of ligands with the receptor. The QSAR models are developed through the use of Multiple Linear Regression (MLR) together with Principal Component Analysis (PCA) methods. The statistical results indicate the multiple correlation coefficient R2 = 0.840, which shows favorable estimation stability, as well as showing a significant correlation between the HCV NS3 protease of the studied compounds and their electron-accepting ability. The POM analysis of the Physico-chemical properties of compounds 1-13, shows that they are bearing (O1, O2) and/or (O1, O2, O3) antiviral pockets, whereby all oxygen atoms are Osp2 and bearing negative charges. Similar to the reference ligand (F9K), the most active compound 10 was bound deeply into the binding cavity of NS3 protease making interactions with the residues Gly137, His57, Ala157, and His528. The anti-hepatitis pharmacophore site is similar to the anti-HIV pharmacophore site.Communicated by Ramaswamy H. Sarma.

Experimental and computational investigations on the anti-corrosive and adsorption behavior of 7-N,N'-dialkyaminomethyl-8-Hydroxyquinolines on C40E steel surface in acidic medium.

Two new 7-N,N'-dialkylaminomethyl-8-Hydroxyquinolines, namely 7-N,N'-dipropylaminomethyl-8-Hydroxyquinoline (DPQ) and 7-N,N'-dimethylaminomethyl-8-Hydroxyquinoline (DMQ), were synthesized and characterized using 1H/13C NMR and Elemental analysis methods. Corrosion inhibition effect of DMP and DPQ for C40E steel in 1 M HCl was evaluated at different concentrations (10-3 to 10-6M) and temperatures (298 to 328 K) using several experimental and computational approaches. Weight loss and electrochemical studies showed that protection efficiencies (ηmax) of DPQ and DMQ increase with increase in concentrations. The DPQ and DMQ showed maximum efficiencies of 96.1% and 94.4%, respectivelyat 10-3 M. Polarization measurements showed that DMQ and DPQ act as mixed type corrosion inhibitors. Adsorption of DPQ and DMQ on C40E steel in 1 M HCl obeyed the Langmuir adsorption isotherm. Variation in surface morphology of corroded metallic surface with and without DMQ and DPQ was demonstrated using scanning electron microscopy. Molecular dynamics (MD) simulations studies showed that DPQ and DMQ acquire the flat or horizontal orientation over the C40E steel. DFT analyses revealed that both DPQ and DMQ interact with the C40E steelusing electron-sharing(donor-acceptor)mechanism. Computational analyses conducted using DFT and MD simulations well corroborate the experimental results.

Synthesis, antibacterial properties and bioinformatics computational analyses of novel 8-hydroxyquinoline derivatives.

New heterocyclic derivatives of 8-hydroxyquinoline were prepared and screened as antimicrobial agents. Chemical structures were elucidated and confirmed using different spectroscopic methods such as elemental analysis data, Infrared, Nuclear Magnetic Resonance Spectroscopy. In order to explore their potential biological activity, the "in vitro" antibacterial activity was investigated against [E. coli (ATCC35218), S. aureus (ATCC29213), V. parahaemolyticus (ATCC17802), and P. aeruginosa (ATCC27853)]. The studied compounds exhibited a remarkable antibacterial activity superior to the standard antibiotic (Penicillin G). These new heterocyclic derivatives of 8-hydroxyquinoline, which proved to be potentially effective, can be used as alternative chemical antimicrobial agents applications. It was very interesting to observe that POM (Petra/Osiris/Molinspiration) bioinformatic analyses of the 8-hydroxyquinoline derivative (5) exhibited more important antibacterial activity (MIC = 10-6 mg/mL against V.p and S.a bacteria) and good drug score (DS = 0.71) when compared with Penicillin (DS = 0.33; MIC = 10-3 mg/mL).

8-Hy-droxy-5-(hy-droxy-meth-yl)quinolin-1-ium chloride.

The title compound, C(10)H(10)NO(2) (+)·Cl(-), contains a quinoline ring system which is essentially planar, with the largest deviation from the mean plane being 0.017 (1) Å. In the crystal, the ion pairs and their inversion-symmetry-related partners are linked by N-H⋯Cl and O-H⋯Cl hydrogen bonds to form tetramers which are further connected through O-H⋯O hydrogen bonds, building infinite one-dimensional chains parallel to the [010] direction.

1,3-Bis[2-hy-droxy-2-(6-meth-oxy-2,2-dimethyl-3a,5,6,6a-tetra-hydro-2H-furo[2,3-d][1,3]dioxol-5-yl)eth-yl]-2,3-dihydro-1H-1,3-benzodiazol-2-one.

In the title benzimidazolone, C(27)H(38)N(2)O(11), which has N-bound glycosidic units, all five-membered O-heterocyclic rings adopt envelope conformations [for the outer rings, the C atom with the dimethyl groups represents the flap atom]. The two glycosidic units are related by a non-crystallographic twofold rotation axis that passes through the carbonyl portion. In the mol-ecular structure, the hy-droxy groups are hydrogen-bond donors to the carbonyl O atom. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

Towards the synthesis of new benzimidazolone derivatives with surfactant properties.

New water-soluble benzimidazolone derivatives were synthesized. In the first approach, di-N-glycosyl and mono-N-alkyl-N-glycosyl compounds were obtained by grafting C-6-activated glycosides onto benzimidazolone. In the second approach, benzimidazolone derivatives bearing a glucosyl unit were synthesized using an efficient glycosylation method. Every compound structure was confirmed by means of NMR spectroscopy and elemental analysis. The preliminary surfactant properties of some compounds were evaluated.