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Synthesis of various symmetric and asymmetric 1,4-DHP linked 1,2,3-triazole derivatives from economical and readily available starting materials via a convenient methodology in a single-pot method ...

In an effort to develop potent anti-inflammatory agents, a series of novel chroman derivatives including acyclic amidochromans, chromanyl esters and chromanyl acrylates have been designed, synthesized and fully characterized. These chroman analogues were screened for their anti-inflammatory activities through inhibition of the TNF-α-induced ICAM-1 expression on human endothelial cells. A structure-activity relationship was also established and it has been found that in the case of carboxy chromans and amidochromans, the chain length of the amide moiety, branching of the side chain and the presence of the substituents on the phenyl ring have significant effects on their inhibitory activities, while in chromanyl acrylates, the number of methoxy groups, their relative positions on the phenyl ring, and presence of functional groups in the α,β-unsaturated ester moiety played a critical role on their activities. Compound 14 (N-hexyl-7-hydroxy-2,2-dimethylchromane-6-carboxamide) was found to be the most potent compound in inhibiting the TNF-α-induced expression of ICAM-1 on endothelial cells. This journal is

A one-pot, four-component methodology have been developed for the synthesis of coumarin-linked triazolyl-dihydropyrimidinones (DHPM). The Biginelli reaction was combined with the click reaction for the first time in a sequential multicomponent tandem reaction approach. A series of ten such compounds have been synthesised and examined for their fluorescent properties. These were found to emit violet-blue light in the visible region of the spectrum with very high Stoke's shift values. The compounds have demonstrated high quantum yields which makes them attractive targets for their utilization as new fluorescent probes. The electronic structure of these coumarin-based donor-pi-acceptor (D-pi-A)-type organic dyes have been studied by Density Functional Theory (DFT). Thermal analysis of few of the compounds show that they are stable up to temperature range of 0-290 degrees C. The synthesised compounds have been characterised by NMR and mass spectrometry.

An efficient palladium-catalysed C H functionalization sequence has been developed for the synthesis of 2-aminoimidazole alkaloids (Kealiinine C) and its analogues. This protocol proceeds via iodocyclisation of propargylguanidines followed by intramolecular Pd-catalysed cyclisation.

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim A microwave-assisted highly efficient intermolecular C−H functionalization sequence has been developed to access substituted isoquinolones using α-amino acid esters as a directing group. This methodology enables a wide range of N-benzoyl α-amino ester derivatives to react via a Ru-catalysed C−H bond activation sequence, to form isoquinolones with moderate to excellent yields. As an additional advantage, our strategy proved to be widely applicable and also enabled the reaction of alkenes to provide access to alkenylated benzamides. The methodology was also extended towards the synthesis of isoquinoline alkaloids derivatives viz. oxyavicine and a dipeptide. The developed protocol is simple and cheap, avoids tedious workup procedures and works efficiently under MW irradiation. (Figure presented.). ispartof: Advanced Synthesis & Catalysis vol:360 issue:16 pages:3083-3089 status: published

Coumarin derivatives possess a wide range of biological activities. By functionalization of the parent coumarin skeleton that has neither antioxidant nor biological activity, a series of new bio-antioxidants has been designed.; Results: New antioxidant compositions (equimolar binary and ternary mixtures) of eight 4-methylcoumarins and three related compounds have been tested and different effects between individual components have been observed: synergism (positive effect), additivism (summary effect) and antagonism (negative effect). Higher oxidative stability of the lipid substrate was obtained in the presence of the new antioxidant compositions of the studied compounds with dl-α-tocopherol and l-ascorbic acid. The role of each component in the antioxidant compositions of ternary mixtures has been identified by using new equations composed by the authors.; Conclusion: All ternary mixtures demonstrate synergism as a result of continuous regeneration of dl-α-tocopherol from the studied antioxidants and l-ascorbic acid. Theoretical calculations have been probed as indicators of the expected effects between the individual components in a binary mixture. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

In this study, novel α-truxillic and β-truxinic acid-based, bio-derived diesters have been developed as internal donors for preparing Ziegler-Natta (ZN) catalysts. Impacts of these bio-derived diesters were investigated on the chemical composition, the morphology, the mode of adsorption, and the propylene polymerization performance of the catalysts in comparison to the most widely used fourth-generation catalyst containing dibutyl phthalate. The molecular structures of the diesters and the particle morphology of the catalysts were preserved in the catalyst preparation. The bio-derived diesters afforded ZN catalysts with a reasonable activity and stereospecificity in propylene polymerization along with similarly broad molecular weight distribution (MWD) as the phthalate-based catalyst. Another promising feature of the catalysts was an opposite hydrogen response in terms of expansion of MWD upon the addition of H2.

Never-ending effort to develop new treatments for malaria, targeting the hemoglobin-degradation in the food vacuole of the parasite is of particular interest because it appears to be critical for the erythrocytic stage parasite development. The Plasmodium aspartic proteinases plasmepsins and cysteine proteases falcipains have been shown to be the major hemoglobin-degrading proteases and are proposed as the high priority drug targets by the World Health Organization for developing novel small molecules as inhibitors of hemoglobin degradation. In the present study, several piperidine and piperazine-based chalcones were assessed for anti-malarial activity against the chloroquine-susceptible P. falciparum 3D7 strain and inhibition of plasmepsin II and falcipain-2. Degradation of hemoglobin by falcipain-2 in the presence or absence of inhibitors was also demonstrated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The IC50 values of chalcones for cell growth inhibition were in the range of 1.60-153.51 μM. IC50 values for cytotoxicity of selected chalcones against Michigan Cancer Foundation (MCF) 7 human breast adenocarcinoma cells were in the range of 8.46-15.64 μM. Molecular docking studies revealed the binding orientation of these chalcones in the active sites of falcipain-2. Our results clearly depict the advantage of these chalcones as they kill P. falciparum malaria parasite in culture, most likely via inhibition of falcipain.

A library of novel 1, 2, 4-oxadiazole linked coumarin dyes have been synthesised via condensation of corresponding acid 6 and N ’-hydroxybenzimidamide 8 . This new class of organic compounds were examined for their fluorescent properties and found to emit blue light in the visible region of the spectrum with very high Stoke's shift values. Most of these compounds demonstrated high quantum yields and fluorescence life time in nano -second range which makes them quite lucrative to be used as new fluorescent probes. The highest quantum yield of 0.68 was shown by compound 9j which also shows high Stoke's shift value. The electronic structure of these coumarin-based donor–π–acceptor (D–π–A)-type organic dyes have been examined by Density Functional Theory (DFT). TGA analysis of few of the compounds show that they are stable up to temperature range of 0–245 °C. The synthesised compounds were characterised by NMR and mass spectrometry and the structure of two of these compounds have been confirmed by X-ray crystallography.

An efficient, catalyst-free, microwave-assisted approach has been developed for the synthesis of 2-aryl/alkyl-3-(1H-benzo[d]imidazol-2-yl)-2,3-dihydroquinazolin-4(1H)-one derivatives by condensing 2-aminobenzamides with various aliphatic, aromatic, and heterocyclic aldehydes. This catalyst-free approach exhibited good functional group compatibility and produced the desired products in good to excellent yields in just 10–20 min. This approach can be seen as a better alternative of the metal-catalyzed protocols used for the synthesis of this class of compounds. The formation of desired compound has also been confirmed by X-ray analysis.

A novel, rapid, and efficient microwave-assisted, metal-free, base-mediated approach has been developed for the construction of benzimidazo[1,2-a]quinazolines from readily available building blocks. This synthetic strategy affords a diverse range of benzimidazo[1,2-a]quinazoline derivatives in moderate to good yields.

The field of nanoscience has blossomed over the last two decades and the importance of nanotechnology has increased in areas such as computing, sensors, biomedicine, and many other applications. In the present study, recent important advances in the functionalization of graphene with an emphasis on the physical properties upon tailored modification have been reviewed. It has been observed that functionalization cannot only stabilize graphene’s unique properties but also introduce some new properties. The functionalization of graphene can be done with different methods like covalent functionalization, non-covalent functionalization, and with the decoration of nanoparticles. In this study, we put forward functionalization of graphene by polymers with different methods such as by direct linking of polymeric chains to the graphene surface or by the controlled growth of the polymeric chains at graphene surface or by decorating with polymers. The exceptional in-plane properties of graphene that are more complete exfoliation of graphite towards single graphene sheets with excellent mechanical, thermal, electrical, and barrier properties. The biological applications for the treatment of deadly diseases like cancer by functionalized nano-graphene oxide (NGO) have reviewed in depth. The application of NGO for drug delivery for gene therapy treatment has also been discussed in this review.

Malaria, particularly in endemic countries remains a threat to the human health and is the leading the cause of mortality in the tropical and sub-tropical areas. Herein, we explored new C2 symmetric hydroxyethylamine analogs as the potential inhibitors of Plasmodium falciparum (P. falciparum; 3D7) in in-vitro cultures. All the listed compounds were also evaluated against crucial drug targets, plasmepsin II (Plm II) and IV (Plm IV), enzymes found in the digestive vacuole of the P. falciparum. Analog 10f showed inhibitory activities against both the enzymes Plm II and Plm IV (Ki, 1.93 ± 0.29 µM for Plm II; Ki, 1.99 ± 0.05 µM for Plm IV). Among all these analogs, compounds 10g selectively inhibited the activity of Plm IV (Ki, 0.84 ± 0.08 µM). In the in vitro screening assay, the growth inhibition of P. falciparum by both the analogs (IC50, 2.27 ± 0.95 µM for 10f; IC50, 3.11 ± 0.65 µM for 10g) displayed marked killing effect. A significant growth inhibition of the P. falciparum was displayed by analog 12c with IC50 value of 1.35 ± 0.85 µM, however, it did not show inhibitory activity against either Plms. The hemolytic assay suggested that the active compounds selectively inhibit the growth of the parasite. Further, potent analogs (10f and 12c) were evaluated for their cytotoxicity towards mammalian HepG2 and vero cells. The selectivity index (SI) values were noticed greater than 10 for both the analogs that suggested their poor toxicity. The present study indicates these analogs as putative lead structures and could serve as crucial for the development of new drug molecules.

A new class of chiral phthalimides functionalized with aryl piperazines was designed anticipating their strong candidature for crystal engineering and technological applications. Five new phthalimides were synthesized, characterized and subjected to single crystal X-ray diffraction study that directed their non-centrosymmetric structures. Four phthalimides crystallized in P21 space group with monoclinic crystal system, however, one was found to possess P212121 space group with orthorhombic system. The supramolecular architectures of phthalimide crystals were analysed by an approach based on consideration of energy of intermolecular interaction. The molecular hyperpolarizability (β) calculation for all the listed phthalimides indicated their promising candidature for NLO materials. Further, the crystalline form of all phthalimides was evaluated for their second harmonic generation (SHG) response. A significant response of 16.4 mV was measured for phthalimide possessing t-butyl substituent at the para position of 4-benzylpiperazine. This high SHG response may be attributed to the molecular chirality and helical supramolecular frameworks stabilized by C-H ⋯O hydrogen bonds in the solid state. The current study attests chiral phthalimides possessing arylpiperazines as effective nominees to the area of crystal engineering and nonlinear optics.

A microwave-assisted highly efficient intermolecular domino carbopalladation/C-H functionalization sequence has been developed to access bis-heteroaryl frameworks in a single operation. The reaction involves carbopalladation of the halogenated acrylamides or phenylpropiolamides by the Pd(0) catalysis, followed by the direct (hetero)arylation to give products with good to excellent yields. The synthetic utility of this method was also extended towards the application of the Ugi-adduct as the starting material.

Despite recent advances in diagnostic and therapeutic methods in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of Candida antarctica lipase (CAL) for the preparation of optically enriched fluconazole analogues. Anti- Aspergillus activity was observed for an optically enriched derivative, (−)- S -2-(2′,4′-difluorophenyl)-1-hexyl-amino-3-(1‴,2‴,4‴)triazol-1‴-yl-propan-2-ol, which exhibits MIC values of 15.6 μg/ml and 7.8 μg/disc in broth microdilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1,000 μg/ml. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analogue exhibited improved antifungal activity against Aspergillus fumigatus (MIC, 1.63 μg/ml). These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotized counterparts, exhibiting anti- Aspergillus activity may have reduced toxicity.

International audience; Background: A library of eleven novel coumarin carboxamides were efficiently synthesized in high yields, by triphenyl phosphite-activated direct condensation of coumarin carboxylic acids and various alkyl amines.Methods: The procedure has several advantages and addresses key “Green” chemistry issues, such as one step condensation, no prior activation of coumarin carboxylic acids by toxic chlorinating agents, no toxic by-products are produced and does not involve troublesome/hazardous disposal of the catalyst. The synthesized coumarin carboxamides were examined for their antiinflammatory activity by measuring the effect on tumour necrosis factor-α (TNF-α) induced expression of intercellular adhesion moledule-1 (ICAM-1).Conclusion: The structure-activity relationship (SAR) studies revealed that N-dodecyl-7- hydroxy-4-methyl-2-oxo-2H-chromene-8-carboxamide (23) exhibited the maximum inhibition (90%) of ICAM-1 expression at an IC50 value of 43 μM.

The aim of this study is to determine, and to compare the protective effects of eight 4-methylcoumarins and four related compounds as radical scavengers and chain-breaking antioxidants. The main kinetic parameters of their radical scavenging activity (as % RSA, stoichiometry, n, and rate constants of reaction with DPPH radical, kRSA) and of chain breaking antioxidant activity (as antioxidant efficiency, PF and reactivity, ID), have been determined and discussed. The RSA study has been conducted at physiological temperature (37 °С) towards DPPH radical and the tested compounds are separated into three main groups: with strong activity (% RSA > 40%); with moderate activity (20% 40%) and with weak activity (% RSA < 20%). Chain-breaking antioxidant activities of the studied compounds have been evaluated during bulk phase lipid (triacylglycerols of sunflower oil, TGSO) autoxidation at 80 °C. All results obtained are compared with those for standard and known inhibitors of oxidation processes, e.g. caffeic and p-coumaric acids, α-tocopherol and butylated hydroxytoluene (BHT). On the basis of a comparative analysis with standard antioxidants, the differences in the radical scavenging and antioxidant abilities of the studied compounds have been discussed and reaction mechanisms proposed. All structures are optimized at UB3LYP/6-31 + G(d,p) level in gas phase and in acetone solution to study the solvation effects.

Highly regioselective acylation has been observed in 7,8-dihydroxy-4-methylcoumarin (DHMC) by the lipase from Rhizopus oryzae suspended in tetrahydrofuran (THF) at 45 °C using six different acid anhydrides as acylating agents. The acylation occurred regioselectively at one of the two hydroxy groups of the coumarin moiety resulting in the formation of 8-acyloxy-7-hydroxy-4-methylcoumarins, which are important bioactive molecules for studying biotansformations in animals, and are otherwise very difficult to obtain by only chemical steps. Six monoacylated, monohydroxy 4-methylcoumarins have been biocatalytically synthesised and identified on the basis of their spectral data and X-ray crystal analysis.

Enzymes, being remarkable catalysts, are capable of accepting a wide range of complex molecules as substrates and catalyze a variety of reactions with a high degree of chemo-, stereo- and regioselectivity in most of the reactions. Biocatalysis can be used in both simple and complex chemical transformations without the need for tedious protection and deprotection chemistry that is very common in traditional organic synthesis. This current review highlights the applicability of one class of biocatalysts viz. ‘‘lipases’’ in synthetic transformations, the resolution of pharmaceutically important small molecules including polyphenols, amides, nucleosides and their precursors, the development of macromolecular systems (and their applications as drug/gene carriers), flame retardants, polymeric antioxidants and nanocrystalline solar cells, etc.

We study changes in the bifurcations of seasonally driven compartmental epidemic models, where the transmission rate is modulated temporally. In the presence of periodic modulation of the transmission rate, the dynamics varies from periodic to chaotic. The route to chaos is typically through period doubling bifurcation. There are coexisting attractors for some sets of parameters. However in the presence of quasiperiodic modulation, tori are created in place of periodic orbits and chaos appears via finite torus doublings. Strange nonchaotic attractors (SNAs) are created at the boundary of chaotic and torus dynamics. Multistability is found to be reduced as a function of quasiperiodic modulation strength. It is argued that occurrence of SNAs gives an opportunity of asymptotic predictability of epidemic growth even when the underlying dynamics is strange.

A novel microwave-assisted protocol has been developed for the selective O-alkylation of aromatic imidate systems with various halides under microwave irradiation using silver carbonate as the base. Products were obtained in short reaction time and in excellent yields.

New isatin-triazole based hybrids have been synthesized and evaluated for their inhibitory activity of TNF-α induced expression of Intercellular Adhesion Molecule-1 (ICAM-1) on the surface of human endothelial cells. Structure-activity relationship (SAR) studies revealed that the presence of the electron-attracting bromo substituent at position-5 of the isatin moiety played an important role in enhancing the anti-inflammatory potential of the synthesized compounds. Z-1-[3-(1H-1,2,4-Triazol-1-yl)propyl]-5-bromo-3-[2-(4-methoxyphenyl)hydrazono]indolin-2-one (19) with an IC50 = 20 μM and 89% ICAM-1 inhibition with MTD at 200 μM was found to be the most potent of all the synthesized derivatives. Introduction of 1,2,4-triazole ring and electron-donating methoxy group on the phenylhydrazone moiety resulted in four-fold increase of the anti-inflammatory activity. ispartof: Journal of Enzyme Inhibition and Medicinal Chemistry vol:31 issue:6 pages:1520-1526 ispartof: location:England status: published