Mohamed Abdaoui

Carbonic Anhydrase Inhibitor Coated Gold Nanoparticles Selectively Inhibit the Tumor-Associated Isoform IX over the Cytosolic Isozymes I and II

An approach for the synthesis of carbonic anhydrase (CA, EC 4.2.1.1) inhibitor coated gold nanoparticles is reported. This nanomaterial selectively inhibited the tumor-associated isoform CA IX overexpressed in hypoxic cancers over the ubiquitous, cytosolic housekeeping isozymes CA I and II and was membrane impermeant. As CA IX has an extracellular active site, the new nanomaterial which is confined to the extracellular space may be useful for imaging and treatment of hypoxic tumors.

Effects of solvent, pH and β-cyclodextrin on the fluorescent behaviour of lomustine

Fluorescent behaviour of lomustine, a DNA cross-linking agent, was investigated in different solvents, pH and in the presence of β-cyclodextrin (β-CD). The solvents in which fluorescence spectra were observed play a major role in determining the spectral intensity of fluorophore, since it was found to exhibit new fluorescent properties essentially influenced by intermolecular interactions, particularly by intermolecular H-bonding formed with solvents. The pH-dependence profile was typically U-shape with a maximum at pH between 3.51 and 6.58. It was corroborated that the fluorescence emission band of lomustine is significantly intensified in the presence of β-CD. From the changes in the fluorescence spectra, it was concluded that β-CD forms a 1:1 inclusion complex with lomustine and its association constant was calculated.

Spectrofluorimetric determination of the antineoplastic agent lomustine based on the sensitizing effect of β-cyclodextrin

The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding on the photophysical properties of the antineoplastic drug lomustine were analysed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The LSER method enabled the overall solvent effects to be quantitatively estimated and separated into specific and non-specific contributions. The molecular encapsulation of lomustine by β-cyclodextrin (β-CD) has been studied using fluorescence spectroscopy. The results are discussed in terms of the binding parameter and the effect of the solvent used. It was concluded that β-CD forms a 1:1 inclusional complex with lomustine in acetonitrile solution and its association constant was calculated to be 500 M(-1). In addition, and for the first time, a simple, rapid and high sensitive fluorimetric method for the determination of lomustine was developed based upon the enhancement effect produced through complex formation with β-CD. The new approach for the quantification of lomustine in the presence of β-CD was described in aqueous and organic solutions. Better limits of detection (0.31 µg ml(-1)) and quantification (1.05 µg ml(-1)) were obtained in aqueous solution with respect to those obtained in organic solvent.

tert-Butyl N-[N,N-bis­(2-chloro­ethyl)sulfamo­yl]-N-(2-chloro­ethyl)carbamate

The title compound, C11H21Cl3N2O4S, was produced as part of a development programme of a new synthetic route to chloroethylnitrososulfamides (CENS) with three chloroethyl moieties. These compounds possess structural features that confer potential biological activity and act as alkylating agents. The packing is governed by four weak C—H⋯O interactions, forming an infinite three-dimensional network.

N′,N′-Dibenzyl-N-(2-chloroéthyl)sulfamide

The title compound, C16H19ClN2O2S, is an intermediate in the set of reactions leading to 2-chloroethylnitrososulfamides (CENS), a new family of promising therapeutic compounds. The asymmetric unit is built up from two molecules linked by an N—H⋯O hydrogen-bond interaction.

N′,N′-Dibenzyl-N-(2-bromoéthyl)sulfamide

The title compound, C16H19BrN2O2S, is an intermediate in the set of reactions leading to 2-bromoethylnitrososulfamides, a new family of promising therapeutic compounds. The molecules are linked by an N—H⋯O hydrogen-bond interaction.

Host-guest complex of nabumetone: β-cyclodextrin: quantum chemical study and QTAIM analysis

The aim of the present work is the investigation of the inclusion complex of nabumetone (NAB) and β-cyclodextrin (β-CD) using PM3, DFT, DFT-D and ONIOM2 methods. The results indicate that the most energetically favorable structure predicts a preference of the methoxy group to enter the cavity of β-CD from its wide rim. Consequently, the butanone moiety is positioned outside the cavity on the side of the secondary hydroxyls, with a total insertion of naphthalene group. The semi-empirical PM3 results are in good agreement with those obtained by the DFT optimization (with and without dispersion correction). The donor–acceptor interactions between drug and the cavity wall of the host, studied on the basis of natural bonding orbital (NBO) analysis, show the presence of weak intermolecular hydrogen bonds in addition to the most important van der Waals interactions. Furthermore, it is revealed that among the DFT and DFT-D techniques selected to quantify these interactions, WB97X-D functional provides the greatest values of stabilization energies E(2). Finally, a detailed topological charge density analysis based on the quantum theory of atoms in molecules (QTAIM), developed by Bader and co-workers, has been accomplished using the WB97X-D and B3LYP methods on the most favorable complexes. A good correlation between the structural parameters and the electronic density is found.

Investigation of charge transfer complexes formed between (S, S)-bis-N,N-sulfonyl bis-L-phenylalanine dimethylester donor with tetracyanoethylene and chloranil as π-acceptors: Experimental and DFT studies

Two novel charge transfer complexes CTC ([D→TCNE] and [D→CHL] : D = (S, S)-bis-N,N-sulfonyl bis-L-phenylalanine dimethylester; TCNE = Tetracyanoethylene; CHL = Chloranil) were synthesized and characterized by elemental analysis: Electronic absorption, spectrophotometric titration, IR. The obtained results indicate the formation of 1:1 for both complexes. The experimental studies were complemented by quantum chemical calculations at DFT/CAM-B3LYP level of theory. Optimized geometrical structures, the electronic spectroscopy, excited-state properties and the descriptions of frontier molecular orbitals were computed and discussed by time-dependent density functional theory (TD-DFT). In addition, vibrational frequency calculations, the natural population analysis (NPA) confirms the presence of intermolecular interactions and natural bonding orbitals (NBO) calculation was carried out in order to elucidate the interactions between TCNE π-acceptor and donor molecule.

Spectroscopic and molecular modelling investigations of supramolecular complex of β-cyclodextrin with N-[(4-sulfonamidophenyl)ethyl]-5-(1,2-dithiolan-3-yl)pentanamide

Spectroscopic investigation supported by molecular modeling methods has been used to describe the inclusion complex of β-cyclodextrin (β-CD) with N-[(4-sulfonamidophenyl) ethyl]-5-(1,2-dithiolan-3-yl) pentanamide in solution and in solid state. By using UV–Vis absorption, the stoichiometric ratio of the complex was found to be 1:1 and the stability constant was evaluated as 1.3415.104 (mol/L)−1. Solid state characterization by FT-IR spectroscopy provided remarkable evidences of the formation of inclusion system. Moreover, semi-empirical calculations using PM3 level of theory and hybrid method ONIOM2 clearly indicate that the formed complexes are energetically favored in vacuum and in solution. From NBO analysis, the mutual interactions between β-CD and SULPA were analyzed and discussed.

Synthesis and Anti-Proliferative Activity of Novel Quinolin-8-ol Derivatives

Through the coupling of substituted benzaldehydes with 8-hydroxy 5-amino methyl quinoline scaffold, a series of new derivatives has been synthesized. In vitro growth inhibitory effects on cancer cell line model have been evaluated. Discussion on the chemical reactivity of these new polycyclic aromatic analogs to generate alkylating species led to the hypothesis that the presence of an imine moiety impedes the formation of quinone methide intermediate and consequently abolishes in part their antiproliferative activity.