Synthesis,cytotoxic assessment,and molecular docking studies of 2,6-diaryl-substituted pyridine and 3,4- dihydropyrimidine-2(1H)-one scaffolds

Cancer is one of the main global health problems. In order to develop novel antitumor agents, we synthesized 3,4-dihydropyrimidine-2(1H)-one (DHPM) and 2,6-diaryl-substituted pyridine derivatives as potential antitumor structures and evaluated their cytotoxic effects against several cancer cell lines. An easy and convenient method is reported for the synthesis of these derivatives, employing cobalt ferrite (CoFe ₂ O ₄ @SiO ₂ -SO ₃ H) magnetic nanoparticles under microwave irradiation and solvent-free conditions. The structural characteristics of the prepared nanocatalyst were investigated by FTIR, XRD, SEM, and TGA techniques. In vitro cytotoxic effects of the synthesized products were assessed against the human breast adenocarcinoma cell line (MCF-7), gastric adenocarcinoma (AGS), and human embryonic kidney (HEK293) cells via MTT assay. The results indicated that compound 4r (DHPM derivative) was the most toxic molecule against the MCF-7 cell line (IC ₅₀ of 0.17 μg/mL). Moreover, compounds 4j and 4r (DHPM derivatives) showed excellent cytotoxic activities against the AGS cell line, with an IC ₅₀ of 4.90 and 4.97 μg/mL, respectively. Although they are pyridine derivatives, compounds 5g and 5m were more active against the MCF-7 cell line. Results showed that the candidate compounds exhibited low cytotoxicity against HEK293 cells. The kinesin Eg5 inhibitory potential of the candidate compounds was evaluated by molecular docking. The docking results showed that, among the pyridine derivatives, compound 5m had the most free energy of binding (–9.52 kcal/mol) and lowest Ki (0.105 μM), and among the pyrimidine derivatives, compound 4r had the most free energy of binding (–7.67 kcal/mol) and lowest Ki (2.39 μM). Ligand-enzyme affinity maps showed that compounds 4r and 5m had the potential to interact with the Eg5 binding site via H-bond interactions to GLU116 and GLY117 residues. The results of our study strongly suggest that DHPM and pyridine derivatives inhibit important tumorigenic features of breast and gastric cancer cells. Our results may be helpful in the further design of DHPMs and pyridine derivatives as potential anticancer agents.     

Development of [(2E,6E)-2,6-bis(4-(dimethylamino)benzylidene)cyclohexanone] as fluorescence-on probe for Hg2+ ion detection: Computational aided experimental studies

Selective metal ion detection is highly desired in fluorometric analysis. In the current study a curcumin-based fluorescence-on probe/[(2E,6E)-2,6-bis(4-(dimethylamino) benzylidene) cyclohexanone]/probe was designed for the removal of one of the most toxic heavy metal ion i.e. Hg²⁺. The structure of the probe was confirmed by FTIR and ¹H NMR spectroscopic analysis displaying distinctive peaks. The complex formation between probe and Hg²⁺ ion was also studied by density functional theory to support the experimental results. Chelation enhanced fluorescence was observed upon interaction with Hg²⁺ ion. Different parameters like pH, effect of mercury ion concentration, contact time, interference study and effect of probe concentration on the fluorescence enhancement were also investigated. A rapid response was detected for Hg²⁺ ion with limit of detection and quantification as 2.7 nM and 3 nM respectively with association constant of 1 × 10¹¹ M^?2. The probe displayed maximum fluorescence intensity at physiological pH. The results showed that the synthesized probe can be employed as an excellent probe for the detection and quantification of Hg²⁺ ions in aqueous samples with high selectivity and sensitivity due to its higher binding energy and larger charge transferring ability.     

Synthesis and Crystal Structure of 4-（4-Bromophenyl）- 3,4-dihydro-6-methyl quinolin-2（1H）-one

The title compound (C16H14BrNO) has been synthesized by the reaction of p-tolylamine, Meldrum’s acid and 4-bromo-benzaldehyde, and its structure was characterized by IR, 1H NMR and X-ray single-crystal diffraction. The crystal belongs to monoclinic, space group P21/n with a = 7.6850(11), b = 8.3004(11), c = 21.301(3) , β = 95.110(2)°, V = 1353.4(3) 3, Mr = 316.19, Z = 4, Dc = 1.552 g/cm3, μ(MoKα) = 3.028 mm-1, F(000) = 640, the final R = 0.0345 and wR = 0.0768. X-ray analysis reveals that the atoms of C(1), C(2), C(3), C(4), C(5) and N(1) form a six-membered ring of boat conformation.     

Synthesis and characterization of new soluble polyamides derived from 2,6-bis(4-aminophenyl)-3,5-dimethyltetrahydro-4H-pyran-4-one

A new oxypyrone diamine, 2,6-bis(4-aminophenyl)-3,5-dimethyltetrahydro-4H-pyran-4-one (DAPP), was prepared from 4-nitrobenzaldehyde and 3-oxa-n-pentane in a two-step reaction with a high yield and a high purity. Aromatic polyamides were obtained from this novel condensation monomer and several diacid chlorides through the conventional low-temperature solution method in N,N-dimethylacetamide. Polycondensation results were consistent with a high reactivity for DAPP because high yields and high molecular weight polyamides were obtained with inherent viscosities up to 1.8 dL/g. The reactivity of DAPP was also estimated with theoretical calculations from computer programs for molecular simulation, with orbital and charge factors considered. The polymers showed improved solubility in organic solvents, relative to conventional wholly aromatic polyamides, and high glass-transition temperatures (from differential scanning calorimetry) over 270 °C. However, the thermal resistance, as estimated by thermogravimetric analysis, was lower than that of conventional aromatic polyamides; nevertheless, decomposition temperatures well beyond 300 °C were observed in nitrogen and air. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1825–1832, 2001     

NBO analysis and vibrational spectra of 2,6-bis(p-methyl benzylidene cyclohexanone) using density functional theory

Vibrational analysis of the 2,6-bis(p-methyl benzylidene cyclohexanone) [PMBC] compound was carried out by using NIR FT-Raman and FT-IR spectroscopic techniques. The equilibrium geometry, various bonding features and harmonic vibrational frequencies of PMBC have been investigated with the help of B3LYP/6-31G(d) density functional theory method. The optimized geometry clearly demonstrates cyclohexanone ring chair conformation is changed into half-chair conformation. The shortening of C–H bond length and blue shifting of the CH stretching wavenumber suggest the existence of improper weak C–HO hydrogen bonding, which is confirmed by the natural bond orbital analysis. The Mulliken population analysis on atomic charges and the HOMO–LUMO energy are also calculated.     

Synthesis of chalcogeno lactones. II. 3, 4-dihydro-1 H-2-benzothiin-3-one, 3,4-dihydro-1H-2-benzoselenin-3-one and 3,4-dihydro-1H-2-benzotellurin-3-one

The synthesis of 3, 4-dihydro-1H-benzothiin-3-one and its selenium and tellurium analogs is reported from o-bromomethylphenylacetyl chloride and sodium hydrogen chalcogenates, via phase-transfer catalysis.     

Novel bent-shaped liquid crystalline compounds II. Synthesis and properties of the 1,3-bis4-[4-(4-alkyloxybenzoyloxy)benzylidene]aminophenoxypropan-2-ols

A series of new symmetric dimer compounds was synthesized, constaining 2-hydroxy-1,3-dioxypropylene as the central linkage and terminal alkyl chains with different lengths. The chemical structures of the liquid crystal dimers (2ES-n) were examined by FTIR and ¹H NMR spectroscopy. Their mesomorphism, thermodynamic properties and optical textures were investigated by differential scanning calorimetry, polarizing optical microscope and X-ray diffraction. For homologues with terminal propyloxy and butyloxy chains, no liquid crystalline phase was observed. Homologues with pentyloxy and hexyloxy terminal chains showed nematic phases, while those with heptyloxy, octyloxy, nonyloxy and decyloxy terminal chains displayed nematic phases and smectic phases. The results confirmed that the liquid crystalline phase changes from nematic to smectic as the terminal chain length increases.     

Molecular structure and vibrational spectra of 2,6-bis(benzylidene)cyclohexanone: a density functional theoretical study

The near-infrared Fourier transform (NIR-FT) Raman and Fourier transform infrared (FT-IR) spectral analyses of 2,6-bis(benzylidene)cyclohexanone (BBC) molecule, a potential drugs for the treatment of P388 leukemia cells, were carried out along with density functional computations. The optimized geometry of BBC using density functional theory shows that the energetically favored chair conformation is not observed for central cyclohexanone ring and is found to possess a nearly ‘half chair’ conformation and shows less expansion of the angles and more rotation about the bonds. The existence of intramolecular C–H?O improper, blue-shifted hydrogen bond was investigated by means of the NBO analysis. The lowering of carbonyl stretching vibration can be attributed to the mesomeric effect and the π-orbital conjugation induced by the unsaturation in the α-carbon atoms and co-planarity of the (–CHC–(CO)–CCH–) group.     

Rearrangements of 4-(2-Aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid diethyl ester

The treatment of 4-(2-aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylic acid diethyl ester (III) with refluxing toluene or pyridine afforded 1,2,3,6-tetrahydro-2,4-dimethyl-2,6-methano-1,3-benzodiazocine-5,11-dicarboxylic acid diethyl ester (IV) as the major product. In addition, the following minor products were isolated: 2-methyl-3-quinolinecarboxylic acid ethyl ester (V), 3-(2-aminophenyl)-5-methyl-6-azabicyclo[3,3,1]-hept-1-ene-2,4-dicarboxylic acid diethyl ester (VI), and 5,6-dihydro-2,4-dimethyl-5-oxobenzo[c][2,7]naphthyridine-1-carboxylic acid ethyl ester (VII). In contrast, acidic conditions caused the conversion of III into V in a 95% yield. The formation of the latter appears to involve IV as an intermediate, since IV degraded rapidly in acid to give V in a quantitative yield.     

2-Amino-5,5-bis(hydroxymethyl)-1,3-thiazol-4(5H)-one and its spirodioxane compounds in the Mannich reaction

It was found that the aminomethylation of 2-amino-5,5-bis(hydroxymethyl)-1,3-thiazol-4(5H)-one and its spiro analogs using primary amines is accompanied by cyclization at the amidine fragment of the molecule with annelation of a tetrahydrotriazine ring. When using secondary amines the aminomethylation occurs at the exocyclic nitrogen atom. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1252–1260, August, 2006.