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In this work, the novel hydrazones and thiosemicarbazones derived from pyrazole moieties were synthesized by reacting 4-chloro-1-methyl-1H-pyrzolecarboxaldehyde with various hydrazides and thiosemicarbazides. All the synthesized compounds were characterized and confirmed with different spectroscopic techniques like FTIR, 1H NMR and LC-MS. The ct-DNA binding interaction studies were evaluated by using UV-visible spectroscopic and fluorescence spectrophotometric techniques with calf thymus DNA. The obtained binding constants of the synthesized were found to be 7 [8.44 × 104] > 4 [3.61 × 104] > 2 [3.60 × 104] > 1 [3.18 × 104] > 8 [2.85 × 104 M-1].

Abstract: Among N-containing heterocycles, pyridine occupies a prominent position due to its presence in nature. Many enzymes in living systems, which are involved in redox reactions, contain pyridine moiety. In addition, its importance in medicinal chemistry and its presence in drugs are well documented. Several pyridine containing compounds are well-known as tubulin polymerization inhibitors and are found to bind with androgen receptors, kinases, carbonic anhydrase and topoisomerase. In recent years, researching have been modifying pyridine containing entities to treat cancer. This review sheds light on recent developments in anticancer studies of pyridine ring-fused heterocyclic compounds.

Abstract: Various catalytic and non-catalytic organic transformations are carried out in glycerol media with superior efficiency over commonly employed organic solvents. The success of glycerol as a green media is due to its exceptional H-bonding properties, which result in enhanced reactivity in many organic transformations. In addition, its highly polar nature and non-toxic properties, recyclability, large availability as an organic waste from the biodiesel industry, high boiling point, low vapor pressure and low price further extend the scope of this solvent as green media. In this review, we present the potential use of glycerol as a green solvent in many organic transformations in two sections: cyclization reactions and miscellaneous reactions.

Kinetic and mechanistic study of cinacalcet hydrochloride by chloramine-B (CAB) in HCl medium at 308 K was the aim of this work. Analyzed the reaction at five different temperatures and determined the thermodynamic parameters using Arrhenius plots. The reaction had a stoichiometry of 1:2 and characterized the oxidation product using chromatographic and spectroscopic methods. The rate law is deduced from the marked effects, which were accompanied by plausible mechanisms.

Background: Xanthatin, fluoropyrimidine and thienopyrimidine, pyrazolopyrimidine, pyrimidine carboxamides, and SKLB1002 are reported as VEGFR2 tyrosine kinase inhibitors. Recently, many studies related to different heterocycles conjugated with dihydroquinazolinones are known to have very good biological activities. In this study, we are intended to explore the cytotoxic studies of piperidine conjugated dihydroquinazolinones against colorectal/colon cancer cell lines and along with molecular docking studies and DFT calculations. Methods: The colorectal/colon cell lines HCT116 and A549 cell lines were treated with these compounds and cytotoxic activities were evaluated by MTT dye uptake method. We performed molecular modelling for compound 3d using the Auto Dock software. The binding of compound 3d with target proteins was studied with the collection of experimentally determined PDB database. Optimized geometry by DFT calculations was performed with B3LYP/6-31G (d) basis set. Results: Piperidine-conjugated dihydroquinazolinone analogues displayed anticancer activity. Particularly, the compound 3d with electron-withdrawing substituents on a phenyl ring showed significant cytotoxicity against HCT116 and A549 cell lines. Molecular docking studies proved that the compound 3d has good fitting by forming hydrogen bonds with amino acid residues at the active sites of VEGFR2. The HOMO, LUMO, their energies and UV visible spectrum were predicted using DFT calculations. Conclusion: Four piperidine-conjugated dihydroquinazolinones were synthesized and evaluated against colorectal and colon cancer cell lines. Compound 3d significantly inhibited the growth of HCT116 and A549. Molecular docking studies displayed good fitting of compound 3d by forming different H-bonds with the amino acid at the active sites of the VEGFR2 target. Using a theoretical approach, we optimized HOMO and LUMO plots for the compound 3d.

Signal transducer and activator of transcription 3 (STAT3) is a tumorigenic transcription factor that is persistently activated in various human cancers including hepatocellular carcinoma (HCC). Therefore, STAT3 is considered as a prominent target to counteract the uncontrolled proliferation of cancer cells. In the present report, pyrimidine-2,4-diones (N-methyluracil derivatives) (MNK1-MNK14) were synthesized in an ionic liquid (BMIm PF6) medium employing a ligand-free Suzuki-Miyaura cross-coupling process. Among the 14 derivatives, compound MNK8 showed good cytotoxicity towards both the tested cell lines and did not display a toxic effect against normal hepatocytes (LO2). MNK8 significantly increased the Sub-G1 cell count in both cell lines and the cytotoxic effect of MNK8 was found to be mediated through the suppression of constitutive phosphorylation of STAT3Y705. It also decreased the DNA interaction ability of nuclear STAT3 in HCC cells. MNK8 downregulated the levels of apoptosis-related proteins (such as Bcl-2, cyclin D1, survivin) and increased cleaved caspase-3 inferring the apoptogenic effect of MNK8. It also reduced the CXCL12-triggered cell migration and invasion in in vitro assay systems. Overall, MNK8 has been demonstrated as a new inhibitor of STAT3 signaling cascade in HCC cells.

Gem-dibromomethylarenes are considered as one of the valuable building blocks in the synthetic field because of their broad range of synthetic applications. These synthons serve as useful intermediates in accessing a varied range of (hetero) aromatic frameworks that can act as vital scaffolds in agrochemicals, medicinal chemistry, material sciences, etc. The additional organic transformations that can be performed using these vital reagents highlights its significance in the area of organic synthesis. This review aims at displaying some discoveries and subsequent improvements of this vital intermediate as an important building block in organic transformations.

A novel series of analogues based on 5-(1-(4-chloro-3-methoxyphenyl)piperidin-4-yl)-4-phenyl-2H-1,2,4-triazole-3(4H)-thione core have been synthesized and their potential as antibacterial, antifungal and antitubercular agents was examined. The structure-activity relationship (SAR) studies of these derivatives 5 (a–k) clearly indicate the vital role of lipophilicity as a major factor in enhancing the biological activity of these compounds. Among the compounds screened, 5a, 5c, 5d, 5j and 5k displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

In the present investigation, novel quinolines have been synthesized and analyzed for their invitro cytotoxic activity against human colon cancer and lung cancer cells. Among the newly synthesized quinoline derivatives, 2-(3-chlorophenyl)-6,7-dimethoxyquinoline (Q6) showed considerable cytotoxic activity against human colon cancer (HCT116) and lung cancer (A549) cell lines with IC50 values of 25.5 ± 2.7 and 32 ± 4.7 μM respectively. Since these quinolines interacted with an Aurora kinase A, we carried out the molecular docking investigation and observed that this quinoline displayed inhibitory potentials. Overall, the compound Q6 was well suited to develop a newer quinolines-based anticancer medication, especially to block cell cycle arrest through Aurora kinase A inhibitors in human cancer.

One pot selective syn diacetoxylation of in situ generated cinnamic esters using PhI(OAc)2/T3P system, started from gem‑dibromomethylarenes in the presence malonoate esters/malononitrile. A broad range of substrates including both electron-deficient and electron-donating gem‑dibromomethylarenes could be efficiently elaborated by this developed methodology thereby furnishing the desired products in good to excellent yields.

In the title compound, C61H15ClN2O3, the heterocyclic ring adopts an envelope conformation, folded across the N...N line, with the 2,5-dimethoxyphenyl unit occupying a quasi-axial site. There are two N—H...O hydrogen bonds in the structure: one hydrogen bond links molecules related by a 41 screw axis to form a C(6) chain, and the other links inversion-related pairs of molecules to form an R 2 2(8) ring. The ring motif links all of the chains into a continuous three-dimensional framework structure. Comparisons are made with the structures of some related compounds.

Two independent N—H⋯O hydrogen bonds link all of the mol­ecules into a continuous three-dimensional framework structure. The quinazoline ring adopts an envelope conformation with the 2,5-di­meth­oxy­phenyl­unit occupying a quasi-axial site., In the title compound, C61H15ClN2O3, the heterocyclic ring adopts an envelope conformation, folded across the N⋯N line, with the 2,5-di­meth­oxy­phenyl unit occupying a quasi-axial site. There are two N—H⋯O hydrogen bonds in the structure: one hydrogen bond links mol­ecules related by a 41 screw axis to form a C(6) chain, and the other links inversion-related pairs of mol­ecules to form an R 2 2(8) ring. The ring motif links all of the chains into a continuous three-dimensional framework structure. Comparisons are made with the structures of some related compounds.

An efficient methodology is reported for the regioselective C-6 arylation of protected uracil via the palladium catalyzed C H functionalization of 1-(4-methoxybenzyl)-3-methylpyrimidine-2,4(1H,3H)-dione with (hetero)aryl halides and boronic acids. Utilization of the Pd(OAc)2/Xantphos catalytic system with a stoichiometric amount of CuI and DBU as the base was vital for the success of this protocol. The methodology is facile and compatible with aryl bromides, iodides and boronic acids and hence affords broad substrate scope and diversity.

One step synthesis of 2,3-dihydroquinazolin-4(1H)-ones from gem-dibromomethylarenes using 2-aminobenzamide is described. Gem-dibromomethylarenes are used as aldehyde equivalent for the efficient synthesis of 2,3-dihydroquinazolin-4(1H)-ones, this synthesis takes shorter reaction time with quick isolation and excellent product yield.

In this paper, we report the synthesis of a nano acid catalyst ZrO2–Al2O3 by using urea as a fuel and the evaluation of its catalytic efficiency in the synthesis of a series of novel substituted dihydroquinazolinones. The catalyst was found to be a highly effective solid acid catalyst, and it exhibited significant catalytic activity in converting substituted 2-aminobenzamides into corresponding 2, 3-dihydroquinazolin-4(1H)-ones under mild conditions. The optimized synthetic method is facile, rapid and efficient and may emerge as one of the best methodologies for accessing pharmaceutically useful dihydroquinazolines.

Propylphosphonic anhydride (T3P®)-DMSO mediated oxidation of alcohols to carbonyl compounds and their subsequent cyclization with aryl/hetero aryl amines and thioglycolic acid to afford 4-thiazolidinones has been reported. Synthesis of 4-thiazolidinones directly from alcohols has been carried out for the first time. Mild reaction conditions, wide functional group tolerance, ease of work-up, and good yields are the noteworthy features of this protocol.

This is an effective, efficient and the easiest method of conversion of substituted 2-aminobenzamides into the corresponding dihydroquinazolinones using gem-dibromomethylarenes under mild reaction conditions.

Propylphosphonic anhydride (T3P®)–DMSO-mediated one-pot three-component synthesis which provides 2-arylquinolines in a single step from benzyl alcohols, anilines, and ethyl vinyl ether by the modif...

Propylphosphonic anhydride (T3P®)–DMSO-mediated one-pot three-component synthesis which provides 2-arylquinolines in a single step from benzyl alcohols, anilines, and ethyl vinyl ether by the modif...

The present work reveals the synthesis and antiproliferative effect of a series of 2, 3 disubstituted 4-thiazolidinone analogues on human leukemic cells. The chemical structures of newly synthesized compounds were confirmed by IR, H-1 NMR, C-13 NMR and mass spectral analysis. Compound methyl 3-methoxy-4-(4-oxo-3-(5-(piperazin-1-yl)pyridin-2-yl)thiazolidin-2-yl)be nzoate (5) displayed potent activity (IC50 9.71, 15.24 and 19.29 mu M) against Nalm6, K562, Jurkat cells. Cell cycle analysis and mitochondrial membrane potential further confirmed that compound 5 is cytotoxic and able to induce cell death. (C) 2014 Elsevier Masson SAS. All rights reserved.

The mild protocol allows the preparation of various biologically interesting thiazole derivatives with a high functional group tolerance.