Abstract Two independent and consecutive intermolecular Michael addition of 1,3-dimethylbarbituric acid to 2,6-diarylidenecyclohexanone as an α,β-unsaturated ketone leads to synthesis of a new type of meso form 5,5′-((2-oxocyclohexane-1,3-diyl)bis(arylmethylene))bis(1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione) in good yield. These compounds showed a 2D-polymeric structure via intermolecular H-bonds. Structure elucidation is carried out by 1H NMR, 13C NMR, FT-IR, and X-ray diffraction analyses. A plausible reaction mechanism is discussed.

Abstract 2-Pyridone is considered as one of the most famous efficient pharmaceutical compounds. Many approaches were discovered to synthesize 2-pyridone. In this present research, chloroacetylation of benzylamine at simple conditions, EtONa/EtCOONa produced N-benzyl-2-chloroacetamide 2. Compound 2 was allowed to react with different reagents. These reagents are acetylacetone, ethyl cyanoacetate, ethyl acetoacetate, and diethyl malonate, creating 2-pyridone derivatives with a good yield. The structures of the prepared compounds were elucidated by spectral data (IR, 1HNMR, and 13CNMR). The synthesized compound was tested for its antimicrobial activity against the Gram-positive (Staphylococcus aureus) and the Gram-negative (Escherichia coli) bacteria. In addition, the antifungal activities of the compounds were tested against two fungi (Candida albicans and Aspergillus flavus). Molecular docking studies were applied using the Autodock vina method. Theoretical methods prove all the experimental results by using molecular docking using Autodock vina and by ADEMT studies. The docking results represent that compound 20 had the best docking free energy, and it is the effective compound toward the selected bacterial and fungal proteins. ADME studies showed that the only compound 18 could cross the blood–brain barrier, and compound 15 was predicted to be soluble.

This study fast synthesizes numerous functionalized pyridoxines using click chemistry and assayed in vitro as inhibitors of the acetylcholinesterase (AChE), butyrylcholinesterase, and two monoamine oxidase (MAO) isoforms, MAO-A and MAO-B. Most of the obtained compounds demonstrate good AChE and selective MAO-B inhibitory activities in the micromolar range, especially one compound, called 4k5 , exhibits excellent inhibitory performance against AChE (IC 50 = 0.0816 ± 0.075 μM) and MAO-B (IC 50 = 0.039 ± 0.003 μM). Finally, a docking study is carried out, demonstrating potential binding orientations and interactions of the compounds in terms of the AChE and MAO-B active sites.

In this study, we evaluated the performance of nano-γ-Fe 2 O 3 –SO 3 H catalyst in the Biginelli reaction and synthesized 3,4-dihydropyrimidine-2-(1 H )-ones. This reaction was carried out under solvent-free and ultrasonic irradiation conditions and belonged to one-pot multicomponent reactions (MCRs) with an adopted aromatic aldehyde, ethyl acetoacetate, and urea as starting materials for the beginning of the reaction. The synthesized materials were efficient in synthesizing 3,4-dihydropyrimidine-2-(1 H )-ones via the Biginelli reaction under reaction conditions. Thus, the advantages of using nano-γ-Fe 2 O 3 –SO 3 H in the Biginelli reaction are short reaction time, high efficiency, green method, solvent free, and cost-effective. Furthermore, nano-γ-Fe 2 O 3 –SO 3 H as a heterogeneous catalyst can be recycled five times without significantly reducing catalytic activity. Graphical abstract

Twelve N-((2-phenyloxazol-4-yl)methyl) pyrimidine carboxamide derivatives were designed, synthesized, and characterized by 1H NMR, 13C NMR, and HRMS. The fungicidal activities of these new compounds against Sclerotinia sclerotiorum, Botrytis cinereal, and Colletotrichum fragariae were evaluated. The results indicated that compounds 5b, 5f, and 5g displayed potential fungicidal activities against tested fungi, especially 5f exhibited IC50 value of 28.9 mg/L against S. sclerotiorum. Moreover, the compounds 5f and 5g showed IC50 values of 54.8 mg/L and 62.2 mg/L against C. fragariae respectively, which shows that they were more active than the commercial fungicide hymexazol. The superficial structure-activity relationships were discussed, which may be of benefit for the development of fungicides and discovery of novel fungicides.

Abstract The present study aimed to design and synthesize a series of phenyl-isoxazole-carboxamide derivatives and investigate their antitumor and antioxidant activities. The in vitro cytotoxic evaluation was conducted using the MTS assay against four cancer cell lines: hepatocellular carcinoma (Hep3B and HepG2), cervical adenocarcinoma (HeLa), breast carcinoma (MCF-7), in addition to the normal cell line (Hek293T). Besides, the antioxidant activity was evaluated using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. All obtained compounds were found to have potent to moderate activities against Hep3B and MCF-7 cancer cells lines, except compound 2e. It was found that compound 2a has potent activity against HeLa and Hep3B cancer cell lines with IC50 values of 0.91 and 8.02 µM, respectively. The IC50 dose range of the tested compounds against Hep3B was 5.96–28.62 µM, except for 2e, compared with doxorubicin, which has an IC50 value of 2.23 µM. Also, the IC50 value range of the compounds against Hek293T was 112.78–266.66 µM, compared with doxorubicin, which has an IC50 dose of 0.581 µM. The antioxidant activity of the synthesized compounds was weak, and compound 2d showed moderate activity against the DPPH enzyme with an IC50 value of 138.50 µM in comparison with Trolox, which has an IC50 dose of 37.23 µM.

In the present study, 3- p -methoxybenzyl/ m -chlorobenzyl/phenyl-4-(3-methyl-2-thienylmethyleneamino)-4,5-dihydro-1 H -1,2,4-triazol-5-ones were obtained from the reaction between 3-methylthiophene-2-carbaldehyde and three different 4-amino-(3- p -methoxybenzyl/ m -chlorobenzyl/phenyl)-4,5-dihydro-1 H -1,2,4-triazole-5-ones. In order to compare experimental and theoretical values, the geometric parameter, electronic, nonlinear optical properties, molecular electrostatic potentials and spectroscopic properties of 3-substituted-4-(3-methyl-2-thienylmethyleneamino)-4,5-dihydro-1 H -1,2,4-triazol-5-ones have been simulated. The electronic properties of the newly synthesized compounds were calculated using DFT/B3LYP and DFT/B3PW91 methods revealing parameters such as ionization potential, electron affinity, energy gap, electronegativity, molecular hardness, molecular softness, electrophilic index, nucleophilic index and chemical potential, all obtained from HOMO and LUMO energies, dipole moments and total energies. UV-visible absorption spectra and the stimulation contributions in UV-visible transitions were obtained by using TD-DFT/B3LYP/6-311G(d,p) and TD-DFT/B3PW91/6-311G(d,p) methods in ethanol. The calculated absorption wavelengths, oscillator power and excitation energies were compared with experimental values. In line with DFT, the numbers of molecular vibration were analyzed through the basis set of 6-311G(d,p). The recording of FT-IR frequencies was done for the pertinent compound. The recorded frequencies through DFT/B3LYP and DFT/B3PW91 methods were compared to experimental values, with a result gained closest to the values of B3LYP. Finally, the Gaussian09W program package in DMSO phase, starting from the optimized structure, has been instrumental in calculating the 13 C-NMR and 1 H-NMR chemical shift values of the GIAO method.

Abstract Novel congeners of naphthalene substituted benzo[c]coumarins (2a-f) were synthesized by reaction of various 3-coumarinoyl methyl pyridinium bromide salts (1a-d) with a selected set of acetyl naphthalene in the presence of sodium acetate in refluxing glacial acetic acid. Structures of the synthesized compounds were confirmed by elemental analysis and by various spectroscopic techniques such as 1H-NMR, 13C-NMR, DEPT, and MS spectral data. Synthesised compounds were screened for antibacterial activity and cytotoxicity against different human cancer cell lines including cervix cancer (HeLa), breast cancer (MCF-7) and lung cancer (A549) using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Although with varying degrees, a significant growth inhibitory and cytotoxic effects were observed on all three cancer cell lines. Compounds 2b and 2e showed significant growth inhibitory and cytotoxicity against aforementioned cancer cell lines.

A Cu(II)-catalyzed Csp 2 -Se and Csp 2 -Sulfur bond formation was achieved with moderate to good yields without the aid of Lewis acid and base. The reaction is compatible with a wide range of heterocycles such as benzothiazole, thiazole, and imidazole. Also, this typical protocol is found to be active in thio-selenation via S-H activation. Additionally, we proposed a plausible mechanistic pathway involving Cu(III) putative intermediate.

Abstract Furocoumarins, such as 8-MOP, are the most common medications used to relieve the symptoms of vitiligo clinically. Some furocoumarins also showed excellent performance in an anti-bacterial assay. This paper describes the synthesis of a series of novel Schiff bases (6a-6k), and their promotion in melanogenesis and anti-bacterial properties were studied in vitro. The pigment production of B16 cells and bacterial inhibition ring assay were applied for the bioactivity of 6a-6k. According to the results, a stronger promotion on pigment content was observed, when six compounds co-cultured with cells, compared with positive control (8-MOP). Significantly, compound 6k (237%) as the most active was found to increase the amount of melanin more than 1.7 times compared with 8-MOP activation rate (136%). All the compounds could moderately retard C. albicans growth. Interestingly, aldehyde 5, which possessed a broader antibacterial spectrum, showed the highest inhibition against C. albicans as well and much better than the positive control (Amphotericin B). Studies of 6k in animal models of vitiligo and related molecular mechanism are presently under way, with the aim of discovering an anti-vitiligo leading compound.

Abstract In this present study, a new axially bis-4-tritylphenoxy substituted silicon phthalocyanine compound was synthesized and characterized using infrared, mass, electronic absorption and nuclear magnetic resonance spectroscopy. Fluorescence and absorption spectra studies of the disubstituted silicon phthalocyanine complex were conducted on the chloroform, dimethyl formamide, dimethyl sulfoxide and tetrahydrofuran solutions. The findings of the fluorescence studies demonstrated that the compound has fluorescence spectra in the different solvents. The effects of the substitution with axially bis-4-tritylphenoxy functionalized groups on these parameters were also compared with the previously synthesized axially disubstituted silicon phthalocyanines. These results proved that the compound has different fluorescence properties in the different solvents.

Abstract In this study, we describe the anion recognition ability of isatin-3-thiosemicarbazone 2, which contains two different anion recognition units i.e. isatin NH and the thiourea moiety. Both have the ability to act as proton donors. Most importantly, a significant colour change of 2 was observed (from light yellow to reddish orange) in organic medium only after the addition of the F– anion. No such colour change could be observed for any other anions including Cl–, Br–, I–, H2PO4−, ${{\text{H}}_{2}}\text{P}{{\text{O}}_{4}}^{-},$ NO2−, $\text{N}{{\text{O}}_{\text{2}}}^{-},$ PF4− $\text{P}{{\text{F}}_{4}}^{-}$etc. The UV-Vis spectroscopic studies also indicate the potential of this compound for selective detection of fluoride anions. 1H-NMR titrations clearly indicate the formation of the 2.F– anionic complex. The Density-functional theory (DFT) calculations are also performed to get further insights on the formation of 2.F– complex.

Abstract A series of novel tetracoumarin derivatives (3a-f) were prepared using the reaction of ether functionalized dibenzaldehyde with 4-hydroxycoumarin in the presence of sodium acetate. The structure of compounds was validated by IR, NMR, and CHN analyzes. Antimicrobial (antibacterial and antifungal) activity was studied on the basis of the minimum bactericidal concentration, minimum inhibitory concentration and inhibitory zone diameter. Favorable biological activity was found in compound 3f.

Abstract An easy and convenient technique for the one-pot synthesis of novel compounds of hexahydroacridine-1,8(2H,5H)-dione and octahydroacridin-10(1H)-yl) thiourea derivatives has been developed by the reaction of the octahydro-1H-xanthenes with hydroxylamine hydrochloride and thiosemicarbazide in ethylene glycol, which is a green solvent, under mild reaction conditions. IR, 1H NMR, 13C NMR spectrometry, and X-ray diffraction analysis were used to identify the structures of these compounds.

Abstract Cancer is one of the most common causes of death in the world. Despite the importance of combating cancer in healthcare systems and research centers, toxicity in normal tissues and the low efficiency of anticancer drugs are major problems in chemotherapy. Nowadays the aim of many medical research projects is to discover new safer and more effective anticancer agents. 1,3,4-Thiadiazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities, including anticancer activities. The aim of this study was to determine the capacity of newly synthesized 1,3,4-thiadiazole compounds as chemotherapeutic agents. The structures of the obtained compounds were elucidated using 1H-NMR, 13C-NMR and mass spectrometry. Although the thiadiazole derivatives did not prove to be significantly cytotoxic to the tumour tissue cultures, compound 4i showed activity against the C6 rat brain cancer cell line (IC50 0.097 mM) at the tested concentrations.

Abstract Spiro[cyclohexane-1,3’-indoline]-2,2’-diones were easily prepared in good to high yields by the oxidation of N-aryl-N-methyl-2-oxocyclohexane-1-carboxamides in one pot with a short reaction time. The spiroindolinediones could be important for the total synthesis of natural products.

Organic electrochemistry is a technique that allows for the heterogeneous redox reactions avoiding both the use of stoichiometric amounts of redox reagents and the resulting formation of stoichiometric by-products. In fact, the redox reagent in these reactions is the electron, which is naturally eco-friendly and produces no side compounds. It is therefore quite obvious that electrochemistry can be classified as a “green” technology. The use of this methodology in the synthesis of β-lactams is not a novelty, but the growing interest in this class of biologically active compounds, due to the discovery of new fields of application (after a moment of decrease in interest due to antibiotic resistance) has been a stimulus for the search for more efficient electrochemical ways to synthesize and transform β-lactams. Thus, this review deals with the twenty-first-century applications of electroorganic technique to the chemistry of β-lactams, by analyzing first the syntheses classified by the type of reactions (cyclization, cycloaddition, etc.) and then by manipulating the β-lactam structure, using it as a synthon. Lastly, the importance of this technique is demonstrated by a study of a pilot plant scale reduction of a cephalosporanic acid derivative to a commercially important antibiotic.

Abstract In this study, some new biscarbazole derivatives were synthesized for the purpose of being used in OLED technologies and related areas. The following compounds: {1,2-bis(2-(3,6-diphenyl-9H-carbazole-9-yl) ethoxy)ethane (C-1), bis[2-(2-(3,6- diphenyl-9H-carbazole-9-yl) ethoxy)etyl]ether (C-2), bis[2-(2-(3,6-di(naphthalene-1-yl)-9H-carbazol-9-yl)ethoxy)etyl]ether (C-3) and bis [2-(2-(3,6-di(naphthalene-2-yl)-9H-carbazol-9-yl)ethoxy) ethyl]ether (C-4) were synthesized by Suzuki-Miyaura Cross Coupling reactions. The structural properties of the synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, and LC-MS. The maximum product yields of 81.6% were obtained for C-4 biscarbazole derivatives. The optical properties were studied using UV-visible and temperature/excitation power density dependent photoluminescence (PL) techniques. The emissions were observed at green and yellow-red color spectral bands. By applying Gaussian fitting to the measured spectra, the superposition of the broad peaks was deconvoluted into two peaks. The origin of emissions was attributed to π- π* transition in aromatic compounds caused by intramolecular charge transfer from host carbazole to these compounds.

Abstract This paper reports the use of rhodium (Rh) catalysts for the oxidative coupling reaction between phenylacetylene and benzaldehyde derivatives via C-H bond activation. These reactions were catalyzed by Rh(l-amino acid)(cod) (the l-amino acid is l-phenylalanine, l-valine or l-proline; cod is 1,5-cyclooctadiene) to obtain chromones in 12.7–88.3% yield. These new Rh catalysts have excellent activity for the coupling reaction between phenylacetylene and different benzaldehyde derivatives. It was found that the electronic effects of the benzaldehyde derivative substituent affected the reaction yield, which is in accordance with the proposed mechanism.

Abstract We have developed a new effective route for obtaining (E)-vinyl-substituted silatranes via ruthenium-catalyzed silylative coupling of 1-allylsilatrane with olefins. Experimental research allowed us also to propose the mechanism of the process based on stoichiometric reactions.