Gheorghita Zbancioc

Synthesis and antituberculosis activity of some new pyridazine derivatives. Part II.

A series of eighteen novel compounds with pyridazine moiety were synthesized and their in vitro antituberculosis activities have been evaluated. A fast, general, and facile method for preparation of pyridazine derivatives in moderate to excellent yields is presented. Three compounds were found to be moderate active against Mycobacterium tuberculosis. Correlation of structure-biological activity has been done.

Diazinium salts with dihydroxyacetophenone skeleton: Syntheses and antimicrobial activity.

Herein we report a feasible study concerning syntheses, structure and antimicrobial activity of some new diazinium salts with dihydroxyacetophenone skeleton. A fast, general, environmentally friendly, and facile method for preparation of diazinium salts under microwave and ultrasounds irradiation is presented. Antimicrobial tests prove that some diazine compounds have a remarkable activity against different microorganisms (germs and fungi), the pyrimidine derivatives being more active. Correlations between structure and antimicrobial activity are reported.

An efficient and selective way to new highly functionalized coronands or spiro derivatives using ultrasonic irradiation.

A new, selective, straightforward and general method for preparation of highly functionalized coronands or spiro derivatives bearing 1,2-dihydroxyacetophenone unit, under conventional conditions and ultrasonic irradiation, is reported. The reaction setup involves only one step, acylation of an α-chloro-3,4-dihydroxyacetophenone with phthaloyl dichloride derivatives. 1,3- and 1,4-Phthaloyl dichloride derivatives leads to coronands only, while 1,2-phthaloyl dichlorides lead either to coronands or to spiro derivatives. A feasible explanation for the different behavior between conventional and ultrasound methods could be the different reaction mechanism involved in the two procedures: tetrahedral nucleophilic substitution under conventional conditions and radical substitution under ultrasound. Ultrasound induces a remarkable acceleration of the reactions (from days to minutes) and, most significantly, the yields are twice as high. A feasible explanation for the efficiency of the reactions under ultrasonic irradiation is presented.

Microwave Assisted Reactions of Some Azaheterocylic Compounds

A fast, general, environmentally friendly and facile method for preparation of five- and six-membered ring diazaheterocylic salts under microwave irradiation is presented. The N-alkylation reactions of imidazole, pyrimidine, pyridazine and phthalazine have been studied. The microwaves remarkably accelerated these N-alkylations, the reaction times decreased dramatically, the reaction conditions were milder, the consumed energy decreased considerably and the amount of solvents used was reduced substantially. Consequently, the microwave assisted alkylation of N-containing heterocycles could be considered eco-friendly. In some cases, under MW irradiation the yields are also higher. A comparative study of microwave vs. classical conditions (liquid solvents) has been done. Twelve new diazaheterocylic salts of potential practical interest were obtained.

Ultrasound and microwave assisted synthesis of dihydroxyacetophenone derivatives with or without 1,2-diazine skeleton

A thorough study concerning O-alkylation and α-bromination of dihydroxyacetophenone (DA) and N-alkylation of 1,2-diazine, under ultrasound (US) and microwave (MW) irradiation as well as under conventional thermal heating (TH) is presented. Under US and MW irradiation the yields are higher, the amount of used solvent decreases substantially, the reaction time decreases considerable (from hours or days to minutes) and the consumed energy decreases, consequently the O-alkylation, α-bromination and N-alkylation methods could be considered environmentally friendly. A selective and efficient way to either bis-O-alkylation or mono-O-alkylation of DA has been found, the relative position of the two hydroxyl groups on the phenyl moiety being compulsory. A selective and efficient way for α-bromination in heterogeneous catalysis of DA derivatives under US irradiation is presented. The N-alkylation reaction of DA under US and MW irradiation proved to be the most convenient setup procedure for these types of reactions. Overall, the use of US proved to be more efficient than MW or TH.

Design, synthesis, and antimicrobial activity of some novel homodrimane sesquiterpenoids with diazine skeleton

Herein we report a feasible study concerning the design, synthesis, and in vitro antimicrobial activity of some novel homodrimane sesquiterpenoids with diazine skeleton. The reaction pathway is efficient and straight, involving the direct N-acylation of diazine with homodrimane sesquiterpenoids bearing acyl chlorides or organic acids functionality. A reliable explication and a feasible reaction mechanism for the obtained compounds are presented. The in vitro antimicrobial activity of the homodrimane sesquiterpenoids with and without diazine skeleton has been evaluated. All the tested compounds have an excellent antibacterial activity against Gram-positive strains S. aureus and B. cereus. SAR correlations concerning antimicrobial activity are reported.Graphical AbstractThe design, synthesis, and in vitro antimicrobial activity of some novel homodrimane sesquiterpenoids with diazine skeleton are described. Antimicrobial tests prove that some homodrimane sesquiterpenoids have an excellent biological activity.

Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity

Abstract The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.

Conformational effects on the lowest excited states of benzoyl-pyrrolopyridazine: insights from PCM time-dependent DFT.

Time-dependent density functional theory (TD-DFT) computations and steady-state electronic spectroscopy measurements are performed on two recently synthesized pyrrolopyridazines to account for the detrimental effect of benzoyl substitution on the blue fluorescence emission. In the case of the highly fluorescent ester derivative, planar in ground state, we show that TD-DFT using the PBE0 and B3LYP hybrid functionals in the state-specific solvation approach provides an accurate description of absorption and emission properties. In benzoyl-pyrrolopyridazine, the (pretwisted) orientations of the benzoyl group and the solvent polarity are both found to modulate the nature of the lowest excited states. The first excited state has nπ* character at ground-state geometry of the main conformer (carbonyl group facing the diazine ring) in nonpolar solvents and become nearly degenerate with a ππ* state in polar solvents. The latter, lower than the nπ* state at the ground state geometry of a minor conformer, relaxes into a twisted intramolecular charge transfer. Experimental absorption and excitation spectra are consistent with the conformational-dependent picture of the lowest excited state (as derived from TD-DFT). A rather qualitative agreement in predicting the fluorescence emission wavelength is achieved in computations employing the CAM-B3LYP and BH&HLYP functionals, whereas global hybrids with low or moderate amounts of exact exchange exhibit the expected TD-DFT failure with up to 1 eV underestimated transition energies.

Interaction of inorganic mercury with CoA-SH and acyl-CoAs

Sulfur containing biomolecules are involved in complexes with mercury. CoA is an important cofactor for many enzymes involved in metabolic processes. Fatty acyl-CoA-thioesters, substrates of mitochondrial ß-oxidation, are sulfur containing compounds and potential mercury ligands. The CoA-Hg2+ complex can be easily assessed by UV-Vis spectroscopy or indirectly by antibacterial tests that reconfirmed the protective role of CoA on E. coli. The characteristics of these complexes were determined by means of FTIR spectroscopy. The reverse phase liquid chromatography combined with electrospray ionization tandem mass spectrometry was used for detection of the side-product that resulted through the cleavage of thioesters in the presence of mercury. An unexpected result was the detection of octathioic acid as a product. Our study shows that mitochondrial β-oxidation can be affected by thioesters depletion assisted by Hg2+. The GC-MS technique could be used to detect some possible mitochondrial injuries due to the heavy metal ions.

Synthesis and in vitro analysis of novel dihydroxyacetophenone derivatives with antimicrobial and antitumor activities.

Herein we report a feasible study concerning the design, syntheses and in vitro antimicrobial and antitumoral activities of some novel compounds with dihydroxyacetophenone (DA) moiety. An efficient and general method for the preparation of diazine with dihydroxyacetophenone (DDA) skeleton under conventional thermal heating (TH), microwave (MW) and ultrasounds (US) irradiation is presented. Antimicrobial and antitumoral tests prove that some dihydroxyacetophenone compounds (the brominated derivatives BrDA 3) have a significant biological activity. It is also to be pointed out that, basically all the dihydroxyacetophenone derivatives proved to have a powerful antibacterial activity against drug resistant Gram-negative strain Pseudomonas aeruginosa ATCC 27853. Of particular interest could be the excellent antibacterial activity of our dihydroxyacetophenone compounds against drug resistant Gram-negative strain Pseudomonas aeruginosa.