Recent Developments of Metal and Metal Oxide Nanocatalysts in Organic Synthesis.

Recently, various nanomaterials have been used in many organic transformations as efficient catalysts. The development of new catalysts by nanoscale design has emerged as a fertile field for research and innovation. The ability of nanotechnology to enhance catalytic activity opens the potential to replace expensive catalysts with lower amounts of inexpensive nanocatalysts. Besides, development of efficient and environmentally friendly synthetic methodologies for the synthesis of compound libraries of medicinal scaffolds is an attractive area of research in both academic and pharmaceutical industry. According to above reports and needs, this review deals with applications of nanoparticles as catalysts in various organic syntheses. We detail the topic of organic transformations using nanoparticles: Metal Nanoparticles and Metal Oxide Nanoparticles. In the latter part, different Metal Oxide Nanoparticles, such as ZnO Nanoparticle, TiO2 Nanoparticle, and CuO Nanoparticle are discussed.

Design, Synthesis and Antitumor Activity of Novel link-bridge and B-Ring Modified Combretastatin A-4 (CA-4) Analogues as Potent Antitubulin Agents.

A series of 12 novel acylhydrazone, chalcone and amide-bridged analogues of combretastatin A-4 were designed and synthesized toward tubulin. All these compounds were determined by elemental analysis, (1)H NMR, and MS. Among them, compound 7 with acylhydrazone-bridge, bearing a benzyl at the indole-N position, was identified as a potent antiproliferative agent against a panel of cancer cell lines with IC50 values ranging from 0.08 to 35.6 µM. In contrast, its cytotoxic effects on three normal human cells were minimal. Cellular studies have revealed that the induction of apoptosis by compound 7 was associated with a collapse of mitochondrial membrane potential, accumulation of reactive oxygen species, alterations in the expression of some cell cycle-related proteins (Cyclin B1, Cdc25c, Cdc2, P21) and some apoptosis-related proteins (Bax, PARP, Bcl-2, Caspase3). The docking mode showed the binding posture of CA-4 and compound 7 are similar in the colchicine-binding pocket of tubulin, as confirmed by colchicine-tubulin competitive binding assay, tubulin polymerization inhibitory activity, extracellular protein expression determination assay and confocal immunofluorescence microscopy. In vivo study, compound 7 effectively inhibited A549 xenograft tumor growth without causing significant loss of body weight suggesting that compound 7 is a promising new antimitotic agent with clinical potential.

A Quinoline-Based Ratiometric and Reversible Fluorescent Probe for Cadmium Imaging in Living Cells.

We report a novel ratiometric and reversible fluorescent probe for Cd(2+) detection utilizing a 6-(dimethylamino)quinaldine derivative as the fluorophore and a 2-hydrazinopyridine derivative as Cd(2+) chelator. This ratiometric fluorescent probe possesses favorable photophysical properties. It shows a large (55 nm) red-shift from 515 nm to 570 nm in the emission spectrum. Moreover, this probe also exhibits an excellent linear relationship of fluorescence intensity ratio (F570/F515) (R(2)=0.989) vs. Cd(2+) concentration in the range of 0-10 µM at physiological pH, which can serve as a "quantitative detecting" probe for Cd(2+). Utilizing this sensitive and selective probe, we have successfully detected Cd(2+) in living cells.

Design, synthesis and biological evaluation of metronidazole-thiazole derivatives as antibacterial inhibitors.

A series of metronidazole-thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, 1H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9µM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5a, 5b, 5d, 5e, 5g and 5i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.

Design, synthesis and biological evaluation of novel 5-phenyl-1H-pyrazole derivatives as potential BRAF(V600E) inhibitors.

A series of novel 5-phenyl-1H-pyrazole derivatives (5 a-5 u) containing niacinamide moiety were synthesized and evaluated for biological activity as potential BRAF(V600E) inhibitors. Among them, compound 5h exhibited the most potent inhibitory activity with an IC50 value of 0.33 µM for BRAF(V600E). Antiproliferative assay results indicated that compound 5h has better antiproliferative activity against WM266.4 and A375 in vitro with IC50 value of 2.63 and 3.16 µM, respectively, being comparable with the positive control vemurafenib. Molecular docking of 5h into the BRAF(V600E) active site was performed to determine the probable binding mode. Furthermore, molecular docking and 3D QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives.

Discovery and molecular modeling of novel 1-indolyl acetate--5-nitroimidazole targeting tubulin polymerization as antiproliferative agents.

A series of 18 novel 1-indolyl acetate-5-nitroimidazole 3a-3r were designed, synthesized, and evaluated for their in vitro biological activities as potential tubulin polymerization inhibitors. Among these compounds, 3p displayed strong antitumor activity with IC50 of 2.00, 1.05, 0.87 µM against A549, Hela and U251 respectively, and also showed the most potent PLK1 inhibitory activity with IC50 of 2.4 µM. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized 1-indolyl acetate-5-nitroimidazolefor potential tubulin polymerization inhibitors.

Design, synthesis and molecular modeling of biquinoline-pyridine hybrids as a new class of potential EGFR and HER-2 kinase inhibitors.

A new series of biquinoline-pyridine hybrids were designed and synthesized by a base-catalyzed cyclocondensation through one-pot multicomponent reaction. All compounds were tested for in vitro anticancer activities against two cancer cell lines A549 (adenocarcinomic human alveolar basal epithelial) and Hep G2 (liver cancer). Enzyme inhibitory activities of all compounds were carried out against EGFR and HER-2 kinase. Of the compounds studied, majority of the compounds showed effective anticancer activity against used cancer cell lines. Compound 9i (IC50=0.09 µM) against EGFR and (IC50=0.2 µM) against HER-2 kinase displayed the most potent inhibitory activity as compared to other member of the series. In the molecular modelling study, compound 9i was bound in to the active pocket of EGFR with four hydrogen bonds and two π-cation interactions having minimum binding energy ΔGb=-54.4 kcal/mol.

Synthesis, biological evaluation and molecular modeling of 1,3,4-thiadiazol-2-amide derivatives as novel antitubulin agents.

A series of 1,3,4-thiadiazol-2-amide derivatives (6a-w) were designed and synthesized as potential inhibitors of tubulin polymerization and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 6f exhibited the most potent anticancer activity against A549, MCF-7 and HepG2 cancer cell lines with IC50 values of 0.03 µM, 0.06 µM and 0.05 µM, respectively. Compound 6f also exhibited significant tubulin polymerization inhibitory activity (IC50=1.73 µM), which was superior to the positive control. The obtained results, along with a 3D-QSAR study and molecular docking that were used for investigating the probable binding mode, could provide an important basis for further optimization of compound 6f as a novel anticancer agent.

Synthesis of caffeic acid amides bearing 2,3,4,5-tetra-hydrobenzo[b][1,4]dioxocine moieties and their biological evaluation as antitumor agents.

A series of caffeic acid amides D1-D17 bearing 2,3,4,5-tetrahydrobenzo-[b][1,4]dioxocine units has been synthesized and their biological activities evaluated for potential antiproliferative and EGFR inhibitory activity. Of all the compounds studied, compound D9 showed the most potent inhibitory activity (IC50=0.79 µM for HepG2 and IC50=0.36 µM for EGFR). The structures of compounds were confirmed by 1H-NMR, ESI-MS and elemental analysis. Among all, the structure of compound D9 ((E)-N-(4-ethoxyphenyl)-3-(2,3,4,5-tetrahydrobenzo[b][1,4]dioxocin-8-yl)acrylamide) was also determined by single-crystal X-ray diffraction analysis. Compound D9 was found to be a potential antitumor agent according to biological activity, molecular docking, apoptosis assay and inhibition of HepG2.

Synthesis, biological evaluation, and molecular docking studies of novel 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety as FAK inhibitors with anticancer activity.

A series of 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety (3a-3r) has been designed, synthesized and their biological activities were also evaluated as potential antiproliferation and focal adhesion kinase (FAK) inhibitors. Among all the compounds, 3p showed the most potent activity in vitro which inhibited the growth of A549 with IC50 value of 3.11 µM and Hela with IC50 value of 2.54 µM respectively. Compound 3p also exhibited significant FAK inhibitory activity (IC50=0.45 µM). Docking simulation was performed for compound 3p into the FAK structure active site to determine the probable binding model.

Design, synthesis and molecular modeling of pyrazole-quinoline-pyridine hybrids as a new class of antimicrobial and anticancer agents.

A new series of pyrazole-quinoline-pyridine hybrids were designed based on molecular hybridization technique and synthesized by a base-catalyzed cyclocondensation reaction through one-pot multicomponent reaction. All compounds were tested for in vitro antibacterial and anticancer activities. Enzyme inhibitory activities of all compounds were carried out against FabH and EGFR. Of the compounds studied, majority of the compounds showed effective antibacterial as well as anticancer activity against used strains and cancer cell lines respectively. Compound 7k (IC50 = 0.51 ± 0.05 µM) against EGFR and 7b displayed the most potent inhibitory activity with IC50 of 3.1 µM against FabH as compared to other member of the series. In the molecular modeling study, compound 7k was bound in to the active pocket of EGFR with three hydrogen bond and one π-cation interaction with minimum binding energy ΔGb = -54.6913 kcal/mol, as well as compound 7b was bound in to the active site of FabH with hydrogen bond and π-sigma interactions with minimum binding energy ΔGb = -45.9125 kcal/mol.

Schiff's base derivatives bearing nitroimidazole and quinoline nuclei: new class of anticancer agents and potential EGFR tyrosine kinase inhibitors.

New Schiff's base derivatives 5a-j have been synthesized by reaction between 2-phenoxyquinoline-3-carbaldehydes 3a-j and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetohydrazide 4 in presence of nickel(II) nitrate as a catalyst in ethanol under reflux in good yield (78-92%). All compounds were tested for anticancer and inhibition of EGFR. Of the compounds studied, majority of the compounds showed effective antiproliferation and inhibition of EGFR and HER-2 activities. Compound 5h showed most effective inhibition (IC50=0.12±0.05 µM) by binding in to the active pocket of EGFR receptor with minimum binding energy (ΔGb=-58.3691 kcal/mol). The binding was stabilized by two hydrogen bonds, two π-cation and one π-sigma interactions. Compound 5d showed most effective inhibition (IC50=0.37±0.04 µM).

Design, synthesis and biological evaluation of metronidazole-thiazole derivatives as antibacterial inhibitors.

A series of metronidazole­thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, (1)H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5 e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9 lM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5 a, 5 b, 5 d, 5 e, 5 g and 5 i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.

Schiff's base derivatives bearing nitroimidazole moiety: new class of antibacterial, anticancer agents and potential EGFR tyrosine kinase inhibitors.

New Schiff's base derivatives 5a-5h have been synthesized by reaction between 1-(4-bromophenyl)-2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanone 3 and various benzohydrazide 4a-4h in presence of nickel (II) nitrate as a catalyst in ethanol at room temperature in good yield (54-88%). All compounds were tested for antibacterial as well as anticancer and inhibition of EGFR. Of the compounds studied, compounds 5d, 5f and 5g in the case of antiproliferation and inhibition of EGFR as well as compounds 5b, 5c, 5e and 5h in the case of antibacterial activity were found to be most effective compounds in the series. Compound 5f shows effective inhibition (IC50=0.21±0.02 µM) by binding in to the active pocket of EGFR receptor with minimum binding energy (ΔGb=-49.4869 kcal/mol).

1,3,4-oxadiazole derivatives as potential biological agents.

The synthesis of novel compound libraries along with screening is a rapid and effective approach for the discovery of potential chemical agents, and it becomes an important method in pharmaceutical chemistry research. 1,3,4- oxadiazole derivatives as the typical heterocyclic compounds, exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel 1,3,4-oxadiazoles derivatives with antimicrobial, antitumor or antiviral activities during the past decade. In this review, we discussed the synthetic development of 1,3,4-oxadiazoles derivatives, and also the relevant bioactivity and their prospects as the potential chemical drugs.

Synthesis and antimicrobial evaluation of new pyrano[4,3-b]pyran and Pyrano[3,2-c]chromene derivatives bearing a 2-thiophenoxyquinoline nucleus.

A new series of pyrano[4,3-b]pyran 4a-i and pyrano[3,2-c]chromene 6a-r derivatives bearing a 2-thiophenoxyquinoline nucleus were synthesized by reaction of 2-(4-(un)-substituted thiophenoxy)quinoline-3-carbaldehydes 2a-i with 6-methyl-4-hydroxypyran-2-one 3 and 4-hydroxy-6-(un)-substituted-2H-chromen-2-one 5a-b respectively and malononitrile at room temperature in the presence of KOH as a basic catalyst. All the compounds were screened against three Gram-positive bacteria (Streptococcus pneumoniae, Bacillus subtilis, Clostridium tetani), three Gram-negative bacteria (Salmonella typhi, Escherichia coli, Vibrio cholerae) and two fungi (Candida albicans, Aspergillus fumigatus) using the broth microdilution MIC (minimum inhibitory concentration) method. Upon antimicrobial screening, it was observed that the majority of the compounds were found to be active against Bacillus subtilis, Clostridium tetani and Candida albicans as compared to standard drugs.

Microwave assisted synthesis and antimicrobial evaluation of new fused pyran derivatives bearing 2-morpholinoquinoline nucleus.

A new series of fused pyran derivatives 5a-x bearing 2-morpholinoquinoline nucleus has been synthesized under microwave irradiation by a reaction of 2-morpholinoquinoline-3-carbaldehyde 2a-c, malononitrile 3 and compounds 4a-h in presence of NaOH as basic catalyst. All the compounds were screened against three Gram positive bacteria (Streptococcus pneumoniae, Clostridium tetani, Bacillus subtilis), three Gram negative bacteria (Salmonella typhi, Vibrio cholerae, Escherichia coli) and two fungi (Aspergillus fumigatus, Candida albicans) using broth microdilution MIC (Minimum Inhibitory Concentration) method. Of the compounds studied, compounds 5b, 5f, 5k, 5m, 5q, 5s and 5v have found to be most efficient members of the series.