The development of low-cost catalytic systems that mimic the activity of tyrosinase enzymes (Catechol oxidase) is of great promise for future biochemistry technologic demands. Herein, we report the synthesis of new biomolecules systems based on hydrazone derivatives containing a pyrazole moiety (L1–L6) with superior catecholase activity. Crystal structures of L1 and L2 biomolecules were determined by X-ray single crystal diffraction (XRD). Optimized geometrical parameters were calculated by density functional theory (DFT) at B3LYP/6–31G (d, p) level and were found to be in good agreement with single crystal XRD data. Copper (II) complexes of the compounds (L1–L6), generated in-situ, were investigated for their catalytic activities towards the oxidation reaction of catechol to ortho-quinone with the atmospheric dioxygen, in an attempt to model the activity of the copper containing enzyme tyrosinase. The studies showed that the activities depend on four parameters: the nature of the ligand, the nature of counter anion, the nature of solvent and the concentration of ligand. The Cu(II)-ligands, given here, present the highest catalytic activity (72.920 μmol·L⁻¹·min⁻¹) among the catalysts recently reported in the existing literature. Full article

The chlorinated ethanoanthracenes: 4,5,12- and 1,8,12-(trichloro-9,10-dihydro-9,10-ethanoanthracene-12-carbonitriles) (1 and 2), which are regioisomers, were synthesized and characterized using nuclear magnetic resonance (¹H- and ¹³C-NMR) and infrared (IR) spectroscopic techniques. The structure of isomer 1 was further confirmed using a single-crystal X-ray technique. The relative stabilities of the title compounds were calculated using the density functional theory (DFT) method on the basis of their total energies and thermodynamic parameters. Isomer 1 is thermodynamically more stable than isomer 2 in the gas phase and in solution. The calculated molecular geometry of isomer 1 agreed well with the experimental X-ray structure. The atomic charge distribution at the different atomic sites was calculated using natural bond orbital analysis. Isomer 2 was predicted to be more polar than isomer 1. Full article

A new series of pyrazolylpyridines was prepared by reaction of ethyl-3-acetyl-1,5-diphenyl-1H-pyrazole-4-carboxylate with the appropriate aldehyde, malononitrile, or ethyl acetoacetate and an excess of ammonium acetate under reflux in acetic acid. Similarly, two novel bipyridine derivatives were prepared by the above reaction using terephthaldehyde in lieu of benzaldehyde derivatives. In addition, a series of 1,2,4-triazolo[4,3-a]pyrimidines was synthesized by a reaction of 6-(pyrazol-3-yl)pyrimidine-2-thione with a number of hydrazonoyl chlorides in dioxane and in the presence of triethylamine. The structure of the produced compounds was established by elemental analyses and spectral methods, and the mechanisms of their formation was discussed. Furthermore, the pyrazolyl-pyridine derivatives were tested as anticancer agents and the results obtained showed that some of them revealed high activity against human hepatocellular carcinoma (HEPG2) cell lines. Full article

A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 8, 4e and 7b have promising activities against the A-549 cell line (IC₅₀ values of 2.78 ± 0.86 μg/mL, 5.37 ± 0.95 μg/mL and 5.70 ± 0.91 μg/mL, respectively) while compound 7b has promising activity against the HepG-2 cell lines (IC₅₀ = 3.54 ± 1.11 μg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results. Full article

A novel series of bis(1,3,4-thiadiazole) derivatives were synthesized in one step methodology with good yields by condensation reaction between bis-hydrazonoyl chloride 1 and various reagents. The structures of the prepared compounds were confirmed by spectral data (IR, NMR, and MS), and elemental analysis. The anticancer activity against human breast carcinoma (MCF-7) cancer cell lines was evaluated in MTT assay. The results revealed that the bis-thiadiazole derivatives 5c,d, 7b,c and 9c had higher antitumor activity than the standard drug Imatinib. Full article

A pyridylpyrazole bearing a hydroxyethyl substituent group has been synthesized by condensation of (Z)-4-hydroxy-4-(pyridin-2-yl)but-3-en-2-one with 2-hydroxyethylhydrazine. The compound was well characterized and its structure confirmed by single crystal X-ray diffraction. Density functional calculations have been performed using DFT method with 6-31G* basis set. The HOMO-LUMO energy gap, binding energies and electron deformation densities are calculated at the DFT (BLYP, PW91, PWC) level. The electrophilic f(−) and nucleophilic f(+) Fukui functions and also the electrophilic and nucleophilic Parr functions are well adapted to find the electrophile and nucleophile centers in the molecule. The title compound has been tested for its DPPH radical scavenging activity which is involved in aging processes, anti-inflammatory, anticancer and wound healing activity. Compound is also found with a significant antioxidant activity, probably due to the ability to donate a hydrogen atom to the DPPH radical. Full article

Molecules bearing β-keto-enol functionality are potential candidates for coordination chemistry. Reported herein is the first synthesis and use of a novel designed ligand based on β-keto-enol group embedded with pyridine and thiophene moieties. The product was prepared in a one-step procedure by mixed Claisen condensation and was characterized by EA, m/z, FT-IR, (¹H, ¹³C) NMR and single-crystal X-ray diffraction analysis. The new structure was grafted onto silica particles to afford a chelating matrix which was well-characterized by EA, FT-IR, solid-state ¹³C-NMR, BET, BJH, SEM and TGA. The newly prepared organic-inorganic material was used as an adsorbent for efficient solid-phase extraction (SPE) of Cu(II), Zn(II), Cd(II) and Pb(II) from aqueous solutions and showed a capture capacity of 104.12 mg·g⁻¹, 98.90 mg·g⁻¹, 72.02 mg·g⁻¹, and 65.54 mg·g⁻¹, respectively. The adsorption capacity was investigated, in a batch method, using time of contact, pH, initial concentration, kinetics (Langmuir and Freundlich models), and thermodynamic parameters (ΔG°, ΔH° and ΔS°) of the system effects. Full article

A novel thiophene-containing compound, 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene (4) was synthesized by reaction of malononitrile with CS₂ in the presence of K₂CO₃ under reflux in DMF and the subsequent reaction with chloroacetone followed by cyclization. This compound has been characterized by means of FT-IR, ¹H-NMR, ¹³C-NMR, and mass spectrometry as well as elemental analysis. In addition, the molecular structures of compound 4 was determined by X-ray crystallography. The geometry of the molecule is stabilized by an intramolecular interaction between N1–H1···O1 to form S6 graf set ring motif. In the crystal, molecules are linked via N1–H2···O1 and C7–H7A···N2 interactions to form a three-dimensional network. Molecular structure and other spectroscopic properties of compound 4 were calculated using DFT B3LYP/6-31G (d,p) method. Results revealed a good agreement between the optimized geometric parameters and the observed X-ray structure. Furthermore, and by employing the natural bond orbital (NBO) method, the intramolecular charge transfer (ICT) interactions along with natural atomic charges at different sites, were calculated; results indicated strong n→π* ICT from LP(1)N5→BD*(2)C15-C16 (63.23 kcal/mol). In addition, the stabilization energy E(2) of the LP(2)O3→ BD*(1)N5-H6 ICT (6.63 kcal/mol) indicated the presence of intramolecular N-H···OH bonding. Similarly, calculations of the electronic spectra of compound 4 using, TD-DFT revealed a good agreement with the experimental data. Finally, compound 4 was evaluated for its in vitro cytotoxic effect against PC-3 and HeLa cell lines, as an anticancer agent, and found to be nontoxic. Full article

Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a one-step procedure by mixed Claisen condensation. All the newly synthesized compounds were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, ESI/LC-MS, elemental analysis, and evaluated for their in vitro antiproliferative activity against breast cancer (MDA-MB241) human cell lines and fungal strains (Fusarium oxysporum f.sp albedinis FAO). Three of the synthesized compounds showed potent activity against fungal strains with IC₅₀ values in the range of 0.055–0.092 µM. The results revealed that these compounds showed better IC₅₀ values while compared with positive controls. Full article

Several series of novel substituted thienothiophene derivatives were synthesized by reacting the synthone 1 with different reagents. The newly synthesized compounds were characterized by means of different spectroscopic methods such as IR, NMR, mass spectrometry and by elemental analyses. The new compounds displayed significant activity against both Gram-positive and Gram negative bacteria, in addition to fungi. Molecular docking and POM analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution doesn’t guaranty more efficiency in bioactivity. Full article

A series of new 2-aminobenzamide derivatives (1–10) has been synthesized in good to excellent yields by adopting both conventional and/or a time-efficient microwave assisted methodologies starting from isatoic anhydride (ISA) and characterized on the basis of their physical, spectral and microanalytical data. Selected compounds of this series were then tested against various bacterial (Bacillus subtilis (RCMB 000107) and Staphylococcus aureus (RCMB 000106). Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB 000103) and fungal strains (Saccharomyces cerevisiae (RCMB 006002), Aspergillus fumigatus (RCMB 002003) and Candida albicans (RCMB 005002) to explore their potential as antimicrobial agents. Compound 5 was found to be the most active compound among those tested, which showed excellent antifungal activity against Aspergillus fumigatus (RCMB 002003) more potent than standard Clotrimazole, and moderate to good antibacterial and antifungal activity against most of the other strains of bacteria and fungi. Furthermore, potential pharmacophore sites were identified and their activity was related with the structures in the solution. Full article

An efficient method for the synthesis of a variety of pyrimidine derivatives 3a–t by reaction of barbituric acids 1a,b as Michael donor with nitroalkenes 2a–k as Michael acceptor using an aqueous medium and diethylamine is described. This 1,4-addition strategy offers several advantages, such as using an economic and environmentally benign reaction media, high yields, versatility, and shorter reaction times. The synthesized compounds were identified by ¹H-NMR, ¹³C-NMR, CHN, IR, and MS. The structure of compound 3a was further confirmed by single crystal X-ray structure determination. Full article

A new chelating matrix, SiNP, has been prepared by immobilizing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel modified with 3-aminopropyl-trimethoxysilane. This new chelating material was well characterized by elemental analysis, FT-IR spectroscopy, cross polarization magic angle spinning solid state ¹³C-NMR, nitrogen adsorption-desorption isotherm, BET surface area, BJH pore size, and scanning electron microscopy (SEM). The new product exhibits good chemical and thermal stability as determined by thermogravimetry curves (TGA). The new prepared material was used as an adsorbent for the solid-phase extraction (SPE) of Pb(II), Cd(II), Cu(II) and Zn(II) from aqueous solutions using a batch method, prior to their determination by flame atomic adsorption spectrometry. The adsorption capacity was investigated using kinetics and pH effects. Common coexisting ions did not interfere with separation and determination. Full article

A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a–i and 4a–e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%–99%). Full article