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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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Giardiasis is a common diarrheal disease worldwide caused by the protozoan parasite Giardia intestinalis. It is urgent to develop novel drugs to treat giardiasis, due to increasing clinical resistance to the gold standard drug metronidazole (MTZ). New potential antiparasitic compounds are usually tested for their killing efficacy against G. intestinalis under anaerobic conditions, in which MTZ is maximally effective. On the other hand, though commonly regarded as an 'anaerobic pathogen,' G. intestinalis is exposed to relatively high O2 levels in vivo, living attached to the mucosa of the proximal small intestine. It is thus important to test the effect of O2 when searching for novel potential antigiardial agents, as outlined in a previous study [Bahadur et al. (2014) Antimicrob. Agents Chemother. 58, 543]. Here, 45 novel chalcone derivatives with triazolyl-quinolone scaffold were synthesized, purified, and characterized by high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance and infrared spectroscopy. Efficacy of the compounds against G. intestinalis trophozoites was tested under both anaerobic and microaerobic conditions, and selectivity was assessed in a counter-screen on human epithelial colorectal adenocarcinoma cells. MTZ was used as a positive control in the assays. All the tested compounds proved to be more effective against the parasite in the presence of O2, with the exception of MTZ that was less effective. Under anaerobiosis eighteen compounds were found to be as effective as MTZ or more (up to three to fourfold); the same compounds proved to be up to >100- fold more effective than MTZ under microaerobic conditions. Four of them represent potential candidates for the design of novel antigiardial drugs, being highly selective against Giardia trophozoites. This study further underlines the importance of taking O2 into account when testing novel potential antigiardial compounds. [ABSTRACT FROM AUTHOR]

Novel phthalimides ( 1, 2, 3) possessing variability of cyclic amines have been synthesized and characterized by analytical and spectroscopic techniques. Phthalimide 1 and 2 crystallized in a triclinic system with space group Pī; however, an orthorhombic system with a chiral space group of P212121 was observed for 3 possessing piperidine cyclic amine. The hydrogen atoms attached to the central chiral carbon were oriented anti to each other resulting in minimum steric repulsion. The occurrence of C-H···O hydrogen bonds in 1, 2, 3 enabled the building of several supramolecular structures. Hyperpolarizability 197.6096 Debye Å2 calculated for 1 was found to be higher than the hyperpolarizabilities, 138.0836 and 165.2521 Debye Å2 measured for 2 and 3, respectively. Subsequently, phthalimides ( 1, 2, 3) were assessed for second harmonic generation (SHG) response, and a negligible response was recorded for 1 and 2; however, 3 showed a significant response of 14.2 mV. In addition to acentric structure, helical structural motifs identified in 3 could be responsible for its enhanced SHG response. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The substitutional effect of Ru on the magnetic and transport properties of double exchange ferromagnets, La0.7Sr0.3MnO3 and La0.5Sr0.5CoO3 has been investigated. It is found that substitution of 10% Ru at the Mn site of La0.7Sr0.3MnO3 decreases the Curie temperature by 20 K than that of the parent compound. However, a large decrease in the Curie temperature, ΔTc∼80 K and the system undergoes a transition from metallic state to insulating state is observed when 10% Ru is doped in La0.5Sr0.5CoO3. The marginal effect of Ru in the Mn–O–Mn sublattice in comparison to the Co–O–Co sublattice could be due to the magnetic exchange interaction between Mn and Ru by virtue of the fact that Ru exhibits variable valence states, Ru+4/Ru+5. The eg and t2g parentage of Ru+5 is similar to Mn+4 and therefore, Ru+5 ion appears to participate in the double exchange mediated ferromagnetic (FM) interaction. On the other hand, Ruthenium (IV) ion disrupts an intermediate spin state of cobalt (Co+3: t2g5eg1), forcing a double exchange FM state to anti-FM state. [Copyright &y& Elsevier]

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 C 2 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 (K i , 1.93 ± 0.29 µM for Plm II; K i , 1.99 ± 0.05 µM for Plm IV). Among all these analogs, compounds 10g selectively inhibited the activity of Plm IV (K i , 0.84 ± 0.08 µM). In the in vitro screening assay, the growth inhibition of P. falciparum by both the analogs (IC 50 , 2.27 ± 0.95 µM for 10f ; IC 50 , 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 IC 50 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. [ABSTRACT FROM AUTHOR]

Phthalimides functionalized with cyclic amines were synthesized, characterized and screened for their in vitro antimalarial efficacy against Plasmodium falciparum ( Pf 3D7). Of all the listed phthalimides evaluated, 14 and 24 were identified as potent antimalarial agents as advocated by assessment of their ability to inhibit [ 3 H] hypoxanthine incorporation in the nucleic acid of parasites. In addition, phthalimides 14 and 24 were incubated for 60 and 90 h and an enhanced antimalarial effect was noticed with increase in time to great extent. A reduction in IC 50 values was observed with increase in exposure time of the parasite to the compounds. A symmetric phthalimide, 24 possessing piperazine as linker unit was identified as the most potent antimalarial agent with IC 50 values of 5.97 ± 0.78, 2.0 ± 1.09 and 1.1 ± 0.75 μM on incubation period of 42, 60 and 90 h, respectively. The abnormal morphologies such as delay in developmental stages, growth arrest and condensed nuclei of parasite were observed with the aid of microscopic studies upon exposure with 14 and 24 . The evaluation of 14 and 24 against chloroquine resistant strain, ( Pf 7GB) of P. falciparum afforded IC 50 values, 13.29 ± 1.20 and 7.21 ± 0.98 μM, respectively. The combination of 24 with artemisinin (ART) showed enhanced killing of parasite against Pf 3D7. Further, all phthalimides were evaluated for their activity against falcipain-2 (FP2), a major hemoglobinase of malarial parasite. The enzymatic assay afforded 6 as most active member against FP2. To the best of our knowledge this is the initial study represents phthalimide protected amino acids functionalized with cyclic amines as potent antimalarial agents. [ABSTRACT FROM AUTHOR]