The Effective Synthesis of New Benzoquinoline Derivatives as Small Molecules with Anticancer Activity.

In this study, some novel benzo[]quinoline derivatives were synthesized, their structural characteristics were described, and their in vitro anticancer efficacy was investigated. The synthesis involves an initial quaternization of the nitrogen atom from benzo[]quinoline and then a [3+2] dipolar cycloaddition reaction of the in situ formed ylide. The effectiveness of synthesis using traditional thermal heating (TH) compared to microwave (MW) and ultrasound (US) irradiation was investigated in detail.

Hybrids Diazine: Recent Advancements in Modern Antimicrobial Therapy.

Nowadays, antimicrobial therapies have become a very challenging issue because of a large diversity of reasons such as antimicrobial resistance, over consumption and misuse of antimicrobial agents, . A modern, actual and very useful approach in antimicrobial therapy is represented by the use of hybrid drugs, especially combined five and six-membered ring azaheterocycles. In this review, we present an overview of the recent advanced data from the last five years in the field of hybrid diazine compounds with antimicrobial activity.

A Review on the Synthesis of Fluorescent Five- and Six-Membered Ring Azaheterocycles.

Azaheterocycles rings with five and six members are important tools for the obtaining of fluorescent materials and fluorescent sensors. The relevant advances in the synthesis of azaheterocyclic derivatives and their optical properties investigation, particularly in the last ten years, was our main objective on this review. The review is organized according to the size of the azaheterocycle ring, 5-, 6-membered and fused ring azaheterocycles, as well as our recent contribution on this research field.

Ultrasound-Assisted Synthesis of Fluorescent Azatetracyclic Derivatives: An Energy-Efficient Approach.

We report here an energy-efficient and straight synthesis of two new classes of derivatized fluorescent azatetracycles under ultrasound (US) irradiation. A first class of azatetracyclic compounds was synthesized by heterogeneous catalytic bromination of the α-keto substituent attached to the pyrrole moiety of the tetracyclic cycloadducts, while for the second, one class was synthesized by nucleophilic substitution of the bromide with the azide group. Comparative with conventional thermal heating (TH) under US irradiation, both types of reactions occur with substantially higher yields, shortened reaction time (from days to hours), lesser energy consumed, easier workup of the reaction, and smaller amounts of solvent required (at least three to five-fold less compared to TH), which make these reactions to be considered as energy efficient.

Ultrasound assisted synthesis of hybrid quinoline-imidazole derivatives: a green synthetic approach.

A green, straightforward and efficient study for obtaining hybrid quinoline-imidazole derivatives under ultrasound (US) irradiation as well as under conventional thermal heating (TH) has been presented. The reaction pathway involves only two steps: the -alkylation of imidazole ring and a Huisgen [3 + 2] dipolar cycloaddition reaction of ylides to dimethyl acetylenedicarboxylate (DMAD). For both types of reactions, a green workup procedure under US irradiation has been presented.

Novel Design of Neuropeptide-Based Drugs with β-Sheet Breaking Potential in Amyloid-Beta Cascade: Molecular and Structural Deciphers.

Our work discusses the investigation of 75 peptide-based drugs with the potential ability to break the β-sheet structures of amyloid-beta peptides from senile plaques. Hence, this study offers a unique insight into the design of neuropeptide-based drugs with β-sheet breaker potential in the amyloid-beta cascade for Alzheimer's disease (AD). We started with five peptides (QKLVFF, KLVFF, LVFF, KLVF and QKLV), to which 14 different organic acids were attached at the N-terminal.

Fluorescent Azasteroids through Ultrasound Assisted Cycloaddition Reactions.

We report here the synthesis and optical spectral properties of several new azasteroid derivatives. The formation of these compounds was explained based on the most probable mechanism. The luminescent heterocycles were synthesized by 1,3-dipolar cycloaddition reactions between benzo[f]quinoline and methylpropiolate or dimethyl acetylenedicarboxylate (DMAD).

Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents.

We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives-(benzo[f]quinolinium salts () and pyrrolobenzo[f]quinolinium cycloadducts ()-were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, H-NMR, C-NMR).

Huisgen [3 + 2] Dipolar Cycloadditions of Phthalazinium Ylides to Activated Symmetric and Non-Symmetric Alkynes.

We present herein a straightforward and efficient pathway for the synthesis of pyrrolophthalazine cycloadducts via Huisgen [3 + 2] dipolar cycloaddition reactions of phthalazinium ylides to methyl propiolate or dimethyl acetylenedicarboxylate (DMAD). A thoroughly comparative study concerning the efficiency of synthesis, conventional thermal heating (TH) versus microwave (MW) and ultrasound (US) irradiation, has been performed. The cycloaddition reactions of phthalazinium ylides to methyl propiolate occur regiospecific, with a single regioisomer being obtained.

Design, Synthesis, Molecular Modelling and Anticancer Activities of New Fused Phenanthrolines.

Three series of fused pyrrolophenanthroline derivatives were designed as analogues of phenstatin and synthesized in two steps starting with 1,7-phenanthroline, 4,7-phenanthroline and 1,10-phenanthroline, respectively. Two (Compounds and ) of the four compounds tested against a panel of sixty human cancer cell lines of the National Cancer Institute (NCI) exhibited significant growth inhibition activity on several cell lines. Compound showed a broad spectrum in terms of antiproliferative efficacy with GI values in the range of 0.

-(imidazole/benzimidazole)-pyridine derivatives: synthesis, structure and antimycobacterial activity.

Over the last decades, few significant achievements have been made in tuberculosis (TB) therapy. As a result, there is an urgent need for new anti-TB drugs. Two new classes of -(imidazole/benzimidazole)-pyridine derivatives were designed, synthesized and evaluated for their antimycobacterial activity.

Microwave Assisted Reactions of Fluorescent Pyrrolodiazine Building Blocks.

We report here the synthesis and optical spectral properties of several new pyrrolodiazine derivatives. The luminescent heterocycles were synthesized by 1,3-dipolar cycloaddition reactions between N-alkylated pyridazine and methylpropiolate or dimethyl acetylenedicarboxylate (DMAD). The pyrrolopyridazine derivatives are blue emitters with moderate quantum yields (around 25%) in the case of pyrrolopyridazines and negligible yet measurable emission for pyrrolophthalazines.

A New Pathway for the Synthesis of a New Class of Blue Fluorescent Benzofuran Derivatives.

In this study an efficient and straightforward method for obtaining a new class of blue fluorescent bezofuran derivatives, under microwave irradiation, as well as under conventional thermal heating, is presented. Under conventional TH the reactions occur selectively, and a single type of benzofuran ester derivative was obtained. The synthesis under MW irradiation also led to benzofuran derivatives, but in a time-dependent manner.

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

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 Cycloaddition of the Benzimidazolium Ylides with Alkynes: New Mechanistic Insights.

New insights concerning the reaction mechanism in the cycloaddition reaction of benzimidazolium ylides to activated alkynes are presented. The proposed pathway leading both to 2-(1H-pyrrol-1-yl)anilines and to pyrrolo[1,2-a]quinoxalin-4(5H)-ones involves an opening of the imidazole ring from the cycloaddition product, followed by a nucleophilic attack of the aminic nitrogen to a proximal carbonyl group and the elimination of a leaving group. The mechanistic considerations are fully supported by experimental data, including the XRD resolved structure of the key reaction intermediate.

Ultrasound assisted synthesis of imidazolium salts: an efficient way to ionic liquids.

In this study a straightforward and efficient approach concerning synthesis of 1,3-diazole derivatives under ultrasound (US) irradiation as well as under conventional thermal heating (TH) is presented. N-alkylation under US irradiation may be considered environmentally friendly in terms of higher yields, smaller amounts of solvent used and an overall energy efficiency due to a substantial reduction of reaction times. A comparative study of ultrasound vs.

Study on the mechanism of ferrite-induced dinitrophenol photodegradation.

We report here the effectiveness of gas chromatography mass spectrometry techniques in establishing the ferrite-associated photocatalytic degradation mechanism of pesticide 2,4-dinitrophenol (2,6-DNP). Unlike the previously discussed DNP-degradation mechanisms that involve either oxidation or reduction reactions, ferrite-based ultraviolet (UV) photodegradation of DNP affords the nontoxic 6-hydroxy-3,5-dinitrohexa-2,4-dienal by an unusual water addition to the benzene core. We searched for and demonstrated the presence of an epoxide of DNP within the photodegradation process, which may unambiguously explain the novel photochemical mechanism.

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.

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.

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.

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.

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.

Silver-induced conformational changes of polypeptides: a CD study.

The role of silver ions in various pathologies, as well as their effect on peptide conformation and properties are less understood. Consequently, we synthesized several peptides with various residues in their sequence to investigate silver-induced conformational changes at various pH values by Circular Dichroism spectroscopy. Uniquely, the glycine-based, histidine-containing peptide showed a severe change from a random coil and β-turn conformation to large α-helices during silver binding.

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.

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.