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New series of chrysin derivatives ( 4a- 4t) were designed and synthesized by introducing different substituted piperazines at C-7 position. Their inhibitory effects on FabH were evaluated using two Gram-negative bacterial strains, Escherichia coli and Pseudomonas aeruginosa, and two Gram-positive bacterial strains, Bacillus subtilis and Staphylococcus aureus. To our delight, most of these compounds exhibited a dramatic increase in inhibitory potency, compared with the control positive drugs. Among them, compound 4s exhibited the most potent inhibitory activity with IC50 values of 5.78 ± 0.24 μ m inhibiting E. coli FabH and potent antibacterial activity against S. aureus and E. coli with MIC of 1.25 ± 0.01, 1.15 ± 0.12 μg/mL, respectively, comparing to the control positive drugs penicillin G (7.56 ± 0.30 μ m). Docking simulation was performed to position compound 4s into the FabH active site, and the result showed that compound 4s could bind well with the FabH as potent FabH inhibitor. [ABSTRACT FROM AUTHOR]

A class of π-conjugated organic synthons, namely 1, 3, 5-tris(2-alkylthiolpyrimidinyl)benzene ( TMPB : alkyl = Me; TEPB : alkyl = Et; TPPB : alkyl = n-Pr) was designed and prepared, which only differ in the length of linear side chain. It was found that these organic synthons can keep a quasi-planar conformation even coordinated to metal ions due to intramolecular C–H⋯N hydrogen bonds. Assembly of these organic synthons with CuX 2 (X = Cl, Br) generated four coordination polymers: [( TPPB )CuCl 2 ] n ( 1 ), {[( TMPB )CuCl 2 ]·H 2 O} n ( 2 ), [( TPPB )CuBr 2 ] n ( 3 ), [( TEPB )CuBr 2 ] n ( 4 ), among which 1 – 3 exhibit one-dimensional coordination ribbon structure and 4 shows a two-dimensional wave-like coordination network. Although 1 – 3 exhibit similar assembly hierarchy going from 1-D ribbon through 2-D supramolecular layer to 3-D supramolecular architecture, the side-chain-effect can be clearly seen which modulates intra-chain or inter-chain Cu⋯Cu distance; inter-chain C–H⋯S supramolecular interactions and even the co-existence of guest water molecules. The room-temperature direct-current (dc) conductivity of 1 – 4 is measured about 9.6 × 10 −12 S cm −1 , 2.9 × 10 −9 S cm −1 , 2.6 × 10 −12 S cm −1 and 5.7 × 10 −11 S cm −1 , respectively, wherein the highest electronic conduction of 2 is assumed to be pertinent to the existence of unique inter-chain C–H⋯S interactions. Furthermore, the complex impedance technique reveals that 2 exhibits a alternate-current (ac) conductivity of 4.3 × 10 −6 S cm −1 at room temperature, which almost decreases linearly with the rising temperature. The higher ac conductivity of 2 against its dc conductivity is assumed to be largely contributed by proton-conduction as the matter of fact that there exist in 2 guest water molecules and water-molecule-associated O–H⋯Cl hydrogen bonding network. The unusual temperature-dependent ac conductivity of 2 is possibly due to the temperature-sensitive O–H⋯Cl hydrogen bonding network, which is responsible for proton transporting. [ABSTRACT FROM AUTHOR]

A series of salicylanilide derivatives (compounds 1-- 32) were synthesised by reacting substituted salicylic acids and anilines. The chemical structures of these compounds were determined by 1H-NMR, electrospray ionisation mass spectrometry (ESI-MS) and elemental analysis. The compounds were assayed for their antiproliferative activities against the Hep-G2 cell line by the 3-(4,5-dimethylthylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Among the compounds tested, 22 and 28 showed the most favouable antiproliferative activities with 50% inhibitory concentration (IC50) values of 1.7 and 1.3 μμM, respectively, which were comparable to the positive control of 5-fluorouracil (IC50 == 1.8 μμM). A solid-phase ELISA assay was also performed to evaluate the ability of compounds 1-- 32 to inhibit the autophosphorylation of the epidermal growth factor receptor tyrosine kinase (EGFR TK). Docking simulations of 22 and 28 were carried out to illustrate the binding mode of the molecule into the EGFR active site, and the result suggested that both compounds 22 and 28 could bind the EGFR kinase well. [ABSTRACT FROM AUTHOR]

Tectorigenin, isolated from the rhizomes of Belamcanda chinensis, shows a wide variety of biological activities. The interest in its biological activities has been matched by a corresponding interest in its synthesis. We herein reported a convenient synthesis of tectorigenin in good yield. The starting material, 2,4,6-trihydroxyanisole, gave the intermediate 2,4,4',6-tetrahydroxy-3-methoxydeoxybenzoin by a Hoesch reaction with 4-hydroxyphenylacetonitrile. The intermediate was then reacted with methanesulfonyl chloride to produce a mixture of tectorigenin and Ψ-tectorigenin. Purification of tectorigenin was unnecessary at this stage as Ψ-tectorigenin in the mixture was isomerized to tectorigenin by refluxing in n-BuOH in the presence of K2CO3. [ABSTRACT FROM AUTHOR]

The compounds (IIId) and (Vc) show most potent inhibitory effects against human carbonic anhydrase inhibitors hCAII and the tumor-associated isozyme hCA IX. [ABSTRACT FROM AUTHOR]

Abstract: Two series of thiazole derivatives containing amide skeleton were synthesized and developed as potent Escherichia coli β-ketoacyl-(acyl-carrier-protein) synthase III (ecKAS III) inhibitors. All the 24 new synthesized compounds were assayed for antibacterial activity against the respective Gram-negative and Gram-positive bacterial strains, including E. coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. In which, 10 compounds with broad-spectrum antibacterial activities were further tested for their ecKAS III inhibitory activity. Last, we have successfully found that compound 4e showed both the promising broad antibacterial activity with MIC of 1.56–6.25μg/mL against the representative bacterial stains, and also processed the most potent ecKAS III inhibitory activity with IC50 of 5.3μM. In addition, docking simulation also carried out in this study to give a potent prediction binding mode between the small molecule and ecKAS III (PDB code: 1hnj) protein. [Copyright &y& Elsevier]

Abstract: A novel efficient method for vapor-phase synthesis of 3-methylindole from aniline and glycerol has been developed over Cu-based catalysts. The catalysts were characterized by BET, XRD, H2-TPR and NH3-TPD techniques. The results indicated that Cu/SiO2-Al2O3 catalyst exhibited high activity. The yield of 3-methylindole could be up to 40% when the Cu loading was 5.41wt% and the reaction temperature was 240°C. Moreover, the catalyst could be reused without obvious loss of the yield even after reaction time of 46h. Copper-based catalyst with good dispersion and large amount of weak acid sites was favorable for producing 3-methylindole. A possible reaction pathway for the catalytic synthesis of 3-methylindole was proposed. [ABSTRACT FROM AUTHOR]

Therapies based on urease inhibition are now seriously considered as the first line of treatment for infections caused by Helicobacter pylori . However, the present inhibitors are ineffective or unstable in highly acidic gastric juice. Here, we report a series of benzylanilines as effective inhibitors of H. pylori urease. Out of the obtained twenty-one compounds, N -(3,4-dihydroxybenzyl)-4-nitroaniline ( 4 ) was evaluated in detail and shows promising features for development as anti- H. pylori agent. Excellent potency against urease in both cell-free extract and intact cell was observed at low concentrations of 4 (IC 50 = 0.62 ± 0.04 and 1.92 ± 0.09 μM), which showed over 29- and 54-fold increase in potency with respect to the positive control AHA. The SAR analysis revealed that protection of 3,4-dihydroxy group of 4 as methoxy or changes of 4-NO 2 will result in a moderate to dramatic decrease in potency. [ABSTRACT FROM AUTHOR]

Many reports implied that the BRAF serine/threonine kinase was mutated in various types of human tumors, which were related with cell growth, survival and differentiation. To provide new therapeutic opportunities, a series of novel 4,5-dihydro-1 H -pyrazole derivatives ( 6a – 10d ) containing thiazole moiety as potential V600E mutant BRAF kinase (BRAF V600E ) inhibitors were designed and synthesized. All compounds were evaluated in vitro for anticancer activities against WM266.4 human melanoma cell line and breast cancer MCF-7 cell line. Compound 10d displayed the most potential antiproliferative activity with an IC 50 value of 0.12 μM against cell line WM266.4 and 0.16 μM against MCF-7 with positive control Sorafenib. Results of the inhibitory activity against BRAF V600E revealed that compound 10d was bearing the best bioactivity with IC 50 of 0.05 μM as well. On the basis of the result of flow cytometry, with the dose of compound 10d increasing, more and more cancer cell gradually encountered apoptosis or died, which indicated the compound 10d could induce remarkable apoptosis of MCF-7 and WM266.4 cells in a dose dependent manner. Furthermore, docking simulation of inhibitor analogues and 3D-QSAR modeling provided potential binding model and further knowledge of pharmacophore. [ABSTRACT FROM AUTHOR]

We report the design and synthesisof a series of new cyclometalatediridium hydrides derived from the C–H bond activation of aromaticnitrones and the biological evaluation of these iridium hydrides asantitumor agents. The nitrone ligands are based on the structure ofa popular antioxidant, α-phenyl-N-tert-butylnitrone (PBN). Compared to cisplatin, the iridium hydridesexhibit excellent antitumor activity on HepG2 cells. The metal-coordinatedcompound with the most potent anticancer activity, 2f, was selected for further analysis because of its ability to induceapoptosis and interact with DNA. During in vitro studies and in vivoefficacy analysis with tumor xenograft models in Institute of CancerResearch (ICR) mice, complex 2fexhibited antitumor activitythat was markedly superior to that of cisplatin. Our results suggest,for the first time, that metal hydrides could be a new type of metal-basedantitumor agent. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives had been designed, synthesized, isolated and evaluated as potentiators of antibacterial agents. All these synthesized compounds were determined by elemental analysis, 1H NMR, and MS. Their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus thuringiensis and Bacillus subtilis by MTT method as potential FabH inhibitory. The results showed that compound 30 exhibited the most potent E. coli FabH inhibitory activity with IC50 of 4.6 μM. Molecular modeling simulation studies were performed in order to predict the biological activities of the proposed compounds. All compounds have been tested for toxicity by MTT assay on human macrophage. [Copyright &y& Elsevier]

Abstract: FabH, β-ketoacyl-acyl carrier protein (ACP) synthase III, is critically important to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of novel secnidazole derivatives (1–20) were synthesized and fully characterized by spectroscopic methods and elemental analysis. Among these compounds, 6, 8, 11, 13, 14, 16–20 were reported for the first time. These compounds were tested for antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. The compounds inhibitory assay and docking simulation indicated that compound 20 (E)-2-(2-methyl-5-nitro-1H-imidazol-1-yl)-N′-(3,4,5-trimethylbenzylidene)acetohydrazide with MIC of 3.13–6.25μg/mL against the tested bacterial strains was a potent inhibitor of Escherichia coli FabH. [Copyright &y& Elsevier]

Abstract: Two vanillin derivatives have been designed and synthesized and their biological activities were also evaluated for antimicrobial activity. Their chemical structures are characterized by single crystal X-ray diffraction studies, 1H NMR, MS, and elemental analysis. Structural stabilization of them followed by intramolecular as well as intermolecular H-bonds makes these molecules as perfect examples in molecular recognition with self-complementary donor and acceptor units within a single molecule. Docking simulations have been performed to position compounds into the FtsZ active site to determine their probable binding model. Compound 3a shows the most potent biological activity, which may be a promising antimicrobial leading compound for the further research. [Copyright &y& Elsevier]

Abstract: A series of novel 4,5-dihydropyrazole derivatives (3a–3t) containing hydroxyphenyl moiety as potential V600E mutant BRAF kinase (BRAFV600E) inhibitors were designed and synthesized. Docking simulation was performed to insert compounds 3d (1-(5-(5-chloro-2-hydroxyphenyl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone) and 3m ( 1-(3-(4-chlorophenyl)-5-(3,5-dibromo-2-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone) into the crystal structure of BRAFV600E to determine the probable binding model, respectively. Based on the preliminary results, compound 3d and 3m with potent inhibitory activity in tumor growth may be a potential anticancer agent. Results of the bioassays against BRAFV600E, MCF-7 human breast cancer cell line and WM266.4 human melanoma cell line all showed several compounds had potent activities IC50 value in low micromolar range, among them, compound 3d and compound 3m showed strong potent anticancer activity, which were proved by that 3d: IC50 =1.31μM for MCF-7 and IC50 =0.45μM for WM266.5, IC50 =0.22μM for BRAFV600E, 3m: IC50 =0.97μM for MCF-7 and IC50 =0.72μM for WM266.5, IC50 =0.46μM for BRAFV600E, which were comparable with the positive control Erlotinib. [Copyright &y& Elsevier]

Abstract: Two series of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives C1–C15 and D1–D15 have been synthesized and evaluated for their B-Raf inhibitory and anti-proliferation activities. Compound C14 ((3-(4-bromophenyl)-5-(2-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanone) showed the most potent biological activity against B-RafV600E (IC50 =0.11μM) and WM266.4 human melanoma cell line (GI50 =0.58μM), being comparable with the positive control Erlotinib and more potent than our previous best compound, while D10 ((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(5-(3-fluorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)methanone) performed the best in the D series (IC50 =1.70μM; GI50 =1.45μM). The docking simulation was performed to analyze the probable binding models and poses and the QSAR model was built for reasonable design of B-Raf inhibitors in future. The introduction of 2,3-dihydrobenzo[b][1,4]dioxin structure reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity. [Copyright &y& Elsevier]

Abstract: A series of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives (5a–8d) have been designed and synthesized, and their biological activities were also evaluated as potential antitumor and cyclin dependent kinase 2 (CDK2) inhibitors. Among all the compounds, compound 5a displayed the most potent CDK2/cyclin E inhibitory activity in vitro, with an IC50 of 0.98±0.06μM. Antitumor assays indicated that compound 5a owned high antiproliferative activity against MCF-7 and B16-F10 cancer cell lines with IC50 values of 1.88±0.11 and 2.12±0.15μM, respectively. Docking simulation was performed to insert compound 5a into the crystal structure of CDK2 at active site to determine the probable binding model. Based on the preliminary results, compound 5a with potent inhibitory activity in tumor growth may be a potential anticancer agent. [Copyright &y& Elsevier]

Abstract: A series of 1,3,4-oxadiazole derivatives derived from 4-methoxysalicylic acid or 4-methylsalicylic acid (6a–6z) have been first synthesized for their potential immunosuppressive activity. Among them, compound 6z displayed the most potent biological activity against lymph node cells (inhibition=38.76% for lymph node cells and IC50 =0.31μM for PI3Kγ). The preliminary mechanism of compound 6z inhibition effects was also detected by flow cytometry (FCM) and the compound exerted immunosuppressive activity via inducing the apoptosis of activated lymph node cells in a dose dependent manner. Docking simulation was performed to position compound 6z into the PI3Kγ structure active site to determine the probable binding model. [Copyright &y& Elsevier]

Abstract: A series of novel chalcone derivatives have been designed and synthesized, and their biological activities were also evaluated as potential inhibitors of tubulin. These compounds were assayed for growth-inhibitory activity against MCF-7 and A549 cell lines in vitro. Compound 3d showed the most potent antiproliferative activity against MCF-7 and A549 cell lines with IC50 values of 0.03 and 0.95μg/mL and exhibited the most potent tubulin inhibitory activity with IC50 of 1.42μg/mL. Docking simulation was performed to insert compound 3d into the crystal structure of tubulin at colchicines binding site to determine the probable binding model. Based on the preliminary results, compound 3d with potent inhibitory activity in tumor growth may be a potential anticancer agent. [Copyright &y& Elsevier]

Abstract: A series of 2,6-dinitro-4-(trifluoromethyl)phenoxysalicylaldoxime derivatives (1h–20h) have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and tubulin polymerization inhibitors. Among all the compounds, 2h showed the most potent activity in vitro, which inhibited the growth of MCF-7, Hep-G2 and A549 cell lines with IC50 values of 0.70±0.05, 0.68±0.02 and 0.86±0.05μM, respectively. Compound 2h also exhibited significant tubulin polymerization inhibitory activity (IC50 =3.06±0.05μM). The result of flow cytometry (FCM) demonstrated that compound 2h induced cell apoptosis. Docking simulation was performed to insert compound 2h into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 2h with potent inhibitory activity in tumor growth may be a potential anticancer agent. [Copyright &y& Elsevier]

Abstract: A series of deoxybenzoin oximes were recently reported as potent immunosuppressive agents by our group. In order to continue the original research for potential immunosuppressive agents with high efficacy and low toxicity, we synthesized a series of new chalcone oximes and evaluated them for their cytotoxicities and immunosuppressive activities. Among the synthesized compounds, chalcone oximes 25 and 27 exhibited lower cytotoxicities and higher inhibitory activities on anti-CD3/anti-CD28 co-stimulated lymph node cells than other compounds. Specially, compound 27 displayed 200-fold lower cytotoxicity (CC50 =2174.39μM) than cyclosporin A (CC50 =10.10μM) and showed SI value (SI=176.69) close to cyclosporin A (SI=154.13). Besides, the preliminary mechanism of inhibition effect of compounds 25 and 27 was also detected by flow cytometry, and the compounds exerted immunosuppressive activities via inducing the apoptosis of activated lymph node cells in a dose dependent manner. Also, the deep mechanism of apoptosis was detected by Western blot analysis. [Copyright &y& Elsevier]

Abstract: A series of 1,3,4-thiadiazol-2-amide derivatives (5a–5y) have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and FAK inhibitors. Among all the compounds, 5h showed the most potent activity in vitro, which inhibited the growth of MCF-7 and B16-F10 cell lines with IC50 values of 0.45 and 0.31μM, respectively. Compound 5h also exhibited significant FAK inhibitory activity (IC50 =5.32μM). Docking simulation was performed to position compound 5h into the FAK structure active site to determine the probable binding model. The results of antiproliferative and Western-blot assay demonstrated that compound 5h possessed good antiproliferative activity. Therefore, compound 5h with potent FAK inhibitory activity may be a potential anticancer agent. [Copyright &y& Elsevier]

Abstract: A series of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan (2a–2s) have been synthesized to screen for FAK inhibitory activity. Compound 2p showed the most potent biological activity against HEPG2 cancer cell line (EC50 =10.28μg/mL for HEPG2 and EC50 =10.79μM for FAK), which was comparable to the positive control. Docking simulation was performed to position compound 2p into the FAK structure active site to determine the probable binding model. The results of antiproliferative and Western-blot assay demonstrated that compound 2p possessed good antiproliferative activity against HEPG2 cancer cell line. Therefore, compound 2p with potent FAK inhibitory activity may be a potential anticancer agent against HEPG2 cancer cell. [Copyright &y& Elsevier]

Abstract: A series of 1,2,4-triazole derivatives containing 1,4-benzodioxan (5a–5q) have been designed, synthesized, structurally determined, and their biological activities were evaluated as potential MetAP2 inhibitors. All the synthesized compounds were first reported. Among the compounds, compound 5k showed the most potent biological activity against HEPG2 cancer cell line (IC50 =0.81μM for HEPG2 and IC50 =0.93μM for MetAP2), which was comparable to the positive control. Docking simulation by positioning compound 5k into the MetAP2 structure active site was performed to explore the possible binding model. The results of apoptosis and Western-blot assay demonstrated that compound 5k possessed good antitumor activity against HEPG2 cancer cell line. Therefore, compound 5k with potent inhibitory activity in tumor growth inhibition may be a potential antitumor agent against HEPG2 cancer cell. [Copyright &y& Elsevier]

Abstract: A series of novel chalcone thiosemicarbazide derivatives (4a–4x) have been designed, synthesized, structurally determined, and their biological activities were also evaluated as potential EGFR kinase inhibitors. All the synthesized compounds are first reported. Among the compounds, compound 4r showed the most potent biological activity (IC50 = 0.78 ± 0.05 μM for HepG2 and IC50 = 0.35 μM for EGFR), which is comparable to the positive controls. Docking simulation was also performed to position compound 4r into the EGFR active site to determine the probable binding model. Antiproliferative assay results demonstrated that some of these compounds possessed good antiproliferative activity against HepG2. Compound 4r with potent inhibitory activity in tumor growth inhibition may be a potential anticancer agent. [Copyright &y& Elsevier]

Abstract: FabH, β-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of o-hydroxybenzylamines 1–16 and its corresponding new urea derivatives 17–32 were synthesized and fully characterized by spectroscopic methods and elemental analysis. This new urea derivatives class demonstrates strong antibacterial activity. Escherichia coli FabH inhibitory assay and docking simulation indicated that the compounds 1-(5-bromo-2-hydroxybenzyl)-1-(4-fluorophenyl)-3-phenylurea (18) and 1-(5-bromo-2-hydroxybenzyl)-1-(4-chlorophenyl)-3-phenylurea (20) were potent inhibitors of E. coli FabH. [Copyright &y& Elsevier]

Abstract: A series of novel cinnamic acid secnidazole ester derivatives have been designed and synthesized, and their biological activities were also evaluated as potential inhibitors of FabH. These compounds were assayed for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. Compounds with potent antibacterial activities were tested for their E. coli FabH inhibitory activity. Compound 3n showed the most potent antibacterial activity with MIC of 1.56–6.25μg/mL against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with IC50 of 2.5μM. Docking simulation was performed to position compound 3n into the E. coli FabH active site to determine the probable binding conformation. [Copyright &y& Elsevier]

Abstract: A series of novel N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassay tests show that compound 4a exhibited high activity against human gastric cancer cell SGC-7901, liver cancer Hep-G2 and human prostate PC-3 cell lines with IC50 values of 21.23±0.99, 29.43±0.32 and 30.89±1.07μM, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results show that compound 4a can inhibit telomerase with IC50 value of 4.0±0.32μM. Docking simulation was performed to position compound 4a into the telomerase (3DU6) active site to determine the probable binding model. [Copyright &y& Elsevier]

Abstract: Thirty-one 3-aryl-4-alkylaminofuran-2(5H)-ones were designed, prepared and tested for their antibacterial activity. Some of them showed significant antibacterial activity against Gram-positive organisms, especially against Staphylococcus aureus ATCC 25923, but all were inactive against Gram-negative organisms. Out of these compounds, 3-(4-bromophenyl)-4-(2-(4-nitrophenyl)hydrazinyl)furan-2(5H)-one (4a11) showed the most potent antibacterial activity against S. aureus ATCC 25923 with MIC50 of 0.42μg/mL. The enzyme assay revealed that the possible antibacterial mechanism of the synthetic compounds might be due to their inhibitory activity against tyrosyl-tRNA synthetase. Molecular dockings of 4a11 into S. aureus tyrosyl-tRNA synthetase active site were also performed. This inhibitor snugly fitting the active site might well explain its excellent inhibitory activity. Meanwhile, this modeling disclosed that a more suitable optimization strategy might be to modify the benzene ring at 3-position of furanone with hydrophilic groups. [Copyright &y& Elsevier]

Abstract: A series of novel chrysin derivatives was firstly synthesized and evaluated on their immunosuppressive activity in the search for potential immunosuppressive agents. Among them, compounds 5c displayed the most potent immunosuppressive inhibitory activity with IC50 of 0.78 μM, which was comparable to that of cyclosporin A (IC50 = 0.06 μM). The preliminary mechanism of compound 5c inhibition effects was also detected by flow cytometry (FCM), and the compound exerted immunosuppressive activity via inducing the apoptosis of activated lymph node cells in a dose dependent manner. Furthermore, the estimated LD50 (in mg/kg) in vivo of compound 5c is 738.2, which indicated that compound 5c was low toxic. [Copyright &y& Elsevier]

Abstract: A series of novel chalcone guanidine derivatives (4a–4q) have been designed and synthesized, and their biological activity were also evaluated as potential antiproliferative and antitubulin polymerization inhibitors. Compound 4q showed the most potent biological activity (IC50 =0.09±0.01μM for MCF-7 and IC50 =8.4±0.6μM for tubulin), which is comparable to the positive controls. Docking simulation was performed to position compound 4q into the colchicine binding site to determine the probable binding model, which suggested probable inhibition mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in the process of cancer angiogenesis. A series of quinoline amide derivatives were prepared and found to be good inhibitors of VEGFR-2. The inhibitory activities were investigated against VEGFR-2 kinase and human umbilical vein endothelial cells (HUVEC) in vitro. Compound 6 (5-chloro-2-hydroxy-N-(quinolin-8-yl)benzamide) exhibited the most potent inhibitory activity (IC50 =3.8 and 5.5nM for VEGFR-2 kinase and HUVEC, respectively). Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the ATP-binding site of VEGFR-2, which demonstrates that compound 6 is a potential agent for cancer therapy deserving further researching. [Copyright &y& Elsevier]

Abstract: A series of new 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety were synthesized. Antiproliferative assay results indicated that compounds 6o and 6u exhibited the most potent activity against gastric cancer cell SGC-7901, which was more potent than the positive control. Especially, compound 6o exhibited significant telomerase inhibitory activity (IC50 =2.3±0.07μM), which was comparable to the positive control ethidium bromide. Docking simulation was performed to position compound 6o into the active site of telomerase (3DU6) to determine the probable binding model. [ABSTRACT FROM AUTHOR]

Abstract: Some pyrogallol and catechol derivatives were synthesized, and their urease inhibitory activity was evaluated by using acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor, as positive control. The assay results indicate that many compounds have showed potential inhibitory activity against H. pylori urease. 4-(4-Hydroxyphenethyl)phen-1,2-diol (2a) was found to be the most potent urease inhibitor with IC50s of 1.5±0.2μM for extracted fraction and 4.2±0.3μM for intact cell, at least 10 times and 20 times lower than those of AHA (IC50 of 17.2±0.9μM, 100.6±13μM), respectively. This finding indicate that 2a would be a potential urease inhibitor deserves further research. Molecular dockings of 2a into H. pylori urease active site were performed for understanding the good activity observed. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel coumarin derivatives containing 4,5-dihydropyrazole moiety as potential telomerase inhibitors were synthesized. The bioassay tests show that compound 3d exhibited potentially high activity against human gastric cancer cell SGC-7901 with IC50 value of 2.69±0.60μg/mL. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results show that compounds 3d and 3f can strongly inhibit telomerase with IC50 values of 2.0±0.07 and 1.8±0.35μM, respectively. Docking simulation was performed to position compound 3d into the telomerase (3DU6) active site to determine the probable binding model. [Copyright &y& Elsevier]

Abstract: Twenty new Schiff bases were synthesized by reacting 5-fluoro-salicylaldehyde and primary amine as potent inhibitors of FabH. These compounds were assayed for antibacterial activity against Escherichia coli, Pseudomonas fluorescence, Bacillus subtilis and Staphylococcus aureus. Compounds with potent antibacterial activities were tested for their E. coli FabH inhibitory activity. (E)-4-fluoro-2-((4-hydroxyphenethylimino)methyl)phenol (10) showed the most potent antibacterial activity with MIC of 1.56–6.25 μg/mL against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with IC50 of 2.7 μM. Docking simulation was performed to position compound 10 into the E. coli FabH active site to determine the probable binding conformation. [ABSTRACT FROM AUTHOR]

Abstract: Fatty acid biosynthesis is essential for bacterial survival. FabH, β-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Fifty-six 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives were synthesized and developed as potent inhibitors of FabH. This inhibitor class demonstrates strong antibacterial activity. Escherichia coli FabH inhibitory assay and docking simulation indicated that the compounds 1-(5-(4-fluorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (12) and 1-(5-(4-chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (13) were potent inhibitors of E. coli FabH. [Copyright &y& Elsevier]

Abstract: A series of novel cinnamic acid metronidazole ester derivatives have been designed and synthesized, and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Compound 3h showed the most potent biological activity (IC50 =0.62μM for EGFR and IC50 =2.15μM for HER-2). Docking simulation was performed to position compound 3h into the EGFR active site to determine the probable binding model. Antiproliferative assay results demonstrated that some of these compounds possessed good antiproliferative activity against MCF-7. Compound 3h with potent inhibitory activity in tumor growth inhibition may be a potential anticancer agent. [Copyright &y& Elsevier]

Abstract: A series of N-alkyl substituted urea derivatives were synthesized and evaluated for their in vitro antibacterial and antifungal activities. The N-alkyl substituted urea derivatives bearing morpholine moiety (3a–3k) showed better activities than those bearing diethylamine moiety (2a–2f). Compounds having fluoro substituent at ortho (3c) and para (3b) positions of the phenyl ring exhibited potent antimicrobial activities against Gram-positive and Gram-negative bacteria as well as fungi. [Copyright &y& Elsevier]

Abstract: Two series of pyrazole derivatives designing for potential EGFR kinase inhibitors have been discovered. Some of them exhibited significant EGFR inhibitory activity. Compound 3-(3,4-dimethylphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (C5) displayed the most potent EGFR inhibitory activity with IC50 of 0.07μM, which was comparable to the positive control erlotinib. Docking simulation was performed to position compound C5 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the pyrazole derivatives own high antiproliferative activity against MCF-7. Compound C5 showed significant antiproliferative activity against MCF-7 with IC50 of 0.08μM. Therefore, compound C5 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent. [Copyright &y& Elsevier]

Abstract: A series of novel dithiocarbamate compounds with the chalcone scaffold have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and antitubulin polymerization inhibitors. Compound 2n showed the most potent biological activity in vitro, which inhibited the growth of MCF-7 cells with IC50 of 0.04±0.01μM and the polymerization of tubulin with IC50 of 6.8±0.6μM. To understand the tubulin–inhibitor interaction and the selectivity of the most active compound towards tubulin, molecular modeling studies were performed to dock compound 2n into the colchicine binding site, which suggested probable inhibition mechanism. [Copyright &y& Elsevier]

Abstract: A series of caffeic acid amides 1–23 were synthesized and nine of which (13–17, 19–21 and 23) were reported for the first time. The chemical structures of these compounds were confirmed by means of 1H NMR, ESI MS and elemental analyses. Compound 15 was determined by single-crystal X-ray diffraction analysis. All of the compounds were assayed for antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT method. Compounds 10–12, 15, 18 and 21 showed considerable antibacterial activities against B. subtilis with MICs of 7.95, 6.25, 3.89, 1.18, 3.12 and 15.5 μg/mL, respectively. Structure–activity relationship analysis disclosed that caffeic acid anilides with electron-donating groups at p-position of benzene ring have better inhibitory activities. [Copyright &y& Elsevier]

Abstract: We described here the design, synthesis, molecular modeling, and biological evaluation of a series of peptide and Schiff bases (PSB) small molecules, inhibitors of Escherichia coli β-Ketoacyl-acyl carrier protein synthase III (ecKAS III). The initial lead compound was reported by us previously, we continued to carry out structure–activity relationship studies and optimize the lead structure to potent inhibitors in this research. The results demonstrated that both N-(2-(3,5-dichloro-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (1f) and 2-hydroxy-N-(2-(2-hydroxy-5-iodobenzylideneamino)propyl)-4-methylbenzamide (3e) posses good ecKAS III inhibitory activity and well binding affinities by bonding Gly152/Gly209 of ecKAS III and fit into the mouth of the substrate tunnel, and can be as potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.20–3.13μg/mL and 0.39–3.13μg/mL against various bacteria. [Copyright &y& Elsevier]

Abstract: A series of N-(2-morpholinoethyl)nicotinamide (1–13) and N-(3-morpholinopropyl)nicotinamide derivatives (14–26) have been designed, synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. Most of these synthesized compounds proved to be potent, and selective inhibitors of MAO-A rather than of MAO-B. 5-Chloro-6-hydroxy-N-(2-morpholinoethyl)nicotinamide (13) displayed the highest MAO-A inhibitory potency (IC50 =0.045μM) and a good selectivity. 2-Bromo-N-(2-morpholinoethyl)nicotinamide (3) was the most potent MAO-B inhibitor with the IC50 value of 0.32μM, but it was not selective. Molecular dockings of compound 13 were performed in order to give structural insights regarding the MAO-A selectivity. [Copyright &y& Elsevier]

Abstract: A series of amide-coupled benzoic nitrogen mustard derivatives as potential EGFR and HER-2 kinase inhibitors were synthesized and reported for the first time. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Of all the studied compounds, compounds 5b and 5t exhibited the most potent inhibitory activity, which was comparable to the positive control erlotinib. Docking simulation was performed to position compounds 5b and 5t into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicated that some of the benzoic nitrogen mustard derivatives possessed high antiproliferative activity against MCF-7. In particular, compounds 5b and 5t with potent inhibitory activity in tumor growth inhibition may function as potential antitumor agents. [Copyright &y& Elsevier]

Abstract: Fourteen metronidazole derivatives (compounds 3a–f and 4b–h) have been synthesized by coupling of metronidazole and salicylic acid derivatives. All of them are reported for the first time. Their chemical structures are characterized by 1H NMR, MS, and elemental analysis. The inhibitory activities against Helicobacter pylori urease have been investigated in vitro and many compounds have showed promising potential inhibitory activities of H. pylori urease. The effect of compounds 4b (IC50 =26μM) and 4g (IC50 =12μM) was comparable with that of acetohydroxamic acid, a well known H. pylori urease inhibitor used as a positive control. The experimental values of IC50 showed that inhibitor was potent urease inhibitor. A docking analysis using the autodock 4.0 program could explain the inhibitory activities of compound 4g against H. pylori urease. [Copyright &y& Elsevier]

Abstract: Microwave irradiation promotes the rapid O,N-acylation–cyclodehydration cascade reaction of oximes and acid chloride. Twenty novel 2,4,5-trisubstituted oxazole derivatives containing heterocycle moiety were synthesized and evaluated for their antiproliferative activity. The twenty compounds are all first reported and their structures were established by elemental analysis, 1H NMR and 13C NMR spectra. The bioassay tests showed that compounds 2-(2-(2-fluorophenyl)-4-(2,3,4-trimethoxyphenyl)oxazol-5-ylthio)benzo[d]thiazole (6af), 2-(2-(pyridin-3-yl)-4-(2,3,4-trimethoxyphenyl)oxazol-5-ylthio)pyrimidine (6bg) and 2-(2-(2-fluorophenyl)-4-(2,3,4-trimethoxyphenyl)oxazol-5-ylthio)-5-methyl-1,3,4-thiadiazole (6cf) displayed good antiproliferative activity in vitro, which were comparable to the positive control (5-fluorouracil). [Copyright &y& Elsevier]

Abstract: Nine 2-arylthiazolidine-4-carboxylic acid derivatives and nine 3-tert-butoxycarbonyl-2-arylthiazolidine-4-carboxylic acid derivatives were synthesized to screen for their antibacterial activities. Compounds 5, 14–18 were first reported. Their chemical structures were clearly determined by 1H NMR, 13C NMR, ESI mass spectra and elemental analyses, coupled with one selected single-crystal structure. All the compounds were assayed for antibacterial activities against two Gram-positive bacterial strains (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538) and two Gram-negative bacterial strains (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525) by MTT method. Most of the 3-tert-butoxycarbonyl-2-arylthiazolidine-4-carboxylic acid derivatives exhibited better antibacterial activities against the four bacterial strains than relative 2-arylthiazolidine-4-carboxylic acid derivatives. Compound (2RS,4R)-3-(tert-butoxycarbonyl)-2-(5-fluoro-2-hydroxyphenyl)thiazolidine-4-carboxylic acid (14) showed powerful antibacterial activities against P. aeruginosa with IC50 value of 0.195μg/mL, which was superior to the positive controls Penicillin G and Kanamycin B, respectively. On the basis of the biological results, structure–activity relationships were discussed. [Copyright &y& Elsevier]

Abstract: Twenty-six depsides were synthesized to screen for their antibacterial activity. All of them were reported for the first time. Their chemical structures were clearly determined by 1H NMR, 13C NMR, ESI mass spectra and elemental analyses, coupled with one selected single-crystal structure. All the compounds were assayed for antibacterial activities against three Gram-positive bacterial strains (Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6538 and Streptococcus faecalis ATCC 9790) and three Gram-negative bacterial strains (Escherichia coli ATCC 35218, Pseudomonas aeruginosa ATCC 13525 and Enterobacter cloacae ATCC 13047) by MTT method. Compound 2-(2-methoxy-2-oxoethyl)phenyl 3-nitrobenzoate (C10) and 2-(2-ethoxy-2-oxoethyl)phenyl 3-nitrobenzoate (C23) showed powerful antibacterial activities against B. subtilis with MIC of 0.78μg/mL while compound 2-(2-methoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate (C8) and 2-(2-ethoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate (C21) exhibited significant antibacterial activities against E. coli with MIC of 1.562μg/mL, which were superior to the positive controls penicillin G and kanamycin B, respectively. On the basis of the biological results, structure–activity relationships were discussed. [Copyright &y& Elsevier]

Abstract: A series of luteolin derivatives 2–20 were prepared, 3–20 of which were first reported. The chemical structures of these compounds were confirmed by means of 1H NMR, ESI-MS and elemental analyses. The compounds were assayed for antibacterial (Bacillus subtilis, Staphylococcus aureus, Pseudomonas fluorescens and Escherichia coli) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trtrazolium bromide) method. Among the compounds tested, most of them displayed significant activity against the tested strains, and 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-hydroxy-7-(2-(3-morpholinopropylamino)ethoxy)-4H-chromen-4-one (17) showed the most favorable antibacterial activity in vitro with MICs of 1.562, 3.125, 3.125, and 6.25μg/mL against B. subtilis, S. aureus, P. fluorescens and E. coli, respectively. Structure–activity relationships (SAR) were also discussed based on the obtained experimental data. [Copyright &y& Elsevier]

Compound (IIIe) is found to exhibit high antiproliferative activity against B16-F10, HeLa, and MCF-7 in vitro. [ABSTRACT FROM AUTHOR]