Journal: Bioorganic chemistry

Article Title: New quinoline/chalcone hybrids as anti-cancer agents: Design, synthesis, and evaluations of cytotoxicity and PI3K inhibitory activity

doi: 10.1016/j.bioorg.2018.10.064

Figure Lengend Snippet: GI 50 of compounds 9i and 9j against 59 cell lines in 9 different cancer panels tested using NCI’s in vitro five dose anticancer assay.

Article Snippet: The presence of such geometry might also be responsible for the absence of the 2-pyrazoline cyclization usually observed in hydrazide-chalcone reactions. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 2. caption a7 Possible stacking interaction for compound 9i . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Scheme 1. caption a7 Synthesis of ( E )- N’ -(( Z )-1-(4-aminophenyl)-3-phenylallylidene)-2-(phenyl)quinoline-4-carbohydrazide derivatives 9a-t . table ft1 table-wrap mode="anchored" t5 caption a7 Panel/cell line GI 50 Compound Panel/cell line GI 50 Compound 9i 9j 9i 9j Leukemia Melanoma CCRF-CEM 5.84 4.53 LOX IMVI 1.56 4.00 HL-60(TB) 2.54 3.49 MALME-3M > 100 > 100 K-562 1.05 3.09 M14 1.16 2.54 MOLT-4 3.30 3.23 MDA-MB-435 0.305 1.00 RPMI-8226 3.86 4.10 SK-MEL-2 2.03 3.81 SR 0.595 3.29 SK-MEL-28 3.78 6.23 Non-small cell lung cancer SK-MEL-5 0.701 2.50 A549/ATCC 2.33 4.79 UACC-257 > 100 33.7 EKVX 3.78 3.99 UACC-62 0.556 2.06 HOP-62 3.21 4.62 Ovarian cancer HOP-92 1.92 4.10 IGROV1 4.98 6.48 NCI-H226 7.54 6.47 OVCAR-3 0.462 2.98 NCI-H23 3.14 5.02 OVCAR-4 1.82 4.71 NCI-H322M 6.00 4.73 OVCAR-5 5.51 8.43 NCI-H460 1.89 3.51 OVCAR-8 4.16 5.25 NCI-H522 0.307 0.622 NCI/ADR-RES 0.519 2.54 Colon cancer SK-OV-3 3.32 4.94 COLO 205 1.99 2.80 Renal cancer HCC-2998 3.40 4.28 786–0 1.84 4.22 HCT-116 1.41 3.18 A498 0.375 1.64 HCT-15 1.03 3.33 ACHN 1.47 4.19 HT29 1.13 3.35 RXF 393 0.698 1.63 KM12 1.15 3.46 SN12C 4.27 6.84 SW-620 1.24 4.24 TK-10 52.30 8.51 CNS cancer UO-31 1.55 2.20 SF-268 2.19 4.09 SF-295 0.540 3.13 Breast cancer SF-539 1.41 2.43 MCF7 0.442 2.53 SNB-19 5.54 6.51 MDA-MB231/ATCC 3.28 3.94 SNB-75 0.371 1.41 HS 578T 1.05 4.68 U251 2.18 4.51 BT-549 2.04 3.92 Prostate cancer T-47D 2.70 2.73 PC-3 2.03 3.40 MDA-MB-468 2.95 4.91 DU-145 3.16 3.68 Open in a separate window GI 50 of compounds 9i and 9j against 59 cell lines in 9 different cancer panels tested using NCI’s in vitro five dose anticancer assay.

Techniques: In Vitro

Journal: Chemical communications (Cambridge, England)

Article Title: Desferrioxamine:gallium-pluronic micelles increase outer membrane permeability and potentiate antibiotic activity against Pseudomonas aeruginosa †

doi: 10.1039/c8cc08134d

Figure Lengend Snippet: F127-DG2 increases the OM permeability of P. aeruginosa. (A) Targeted F127-DG2/TPE micelles exhibit greater binding to the OM of P. aeruginosa than untargeted F127/TPE micelles based on increased TPE fluorescence (blue). F127-DG2/TPE does not target E. coli due to lack of the necessary OM receptors. Positive control staining performed with FM 4-64FX (red). (B) OM permeabilization with F127-DG2 (64 µM) results in greater HI accumulation (red) in P. aeruginosa than unmodified F127 (64 µM) + DG (128 µM), while E. coli OM permeability is unchanged. Positive control staining performed with SYTO13 (green). (C) NCF hydrolysis occurs more rapidly in P. aeruginosa treated with F127-DG2 (128 µM) than unmodified F127 (128 µM) + DG (256 µM); E. coli OM permeability is unaffected by either polymer. Scale bars represent 2 µm.

Article Snippet: Neither F127-DG 2 nor F127 plus DG potentiated antibiotic activity against E. coli due to lack of the necessary OM receptors for DG. table ft1 table-wrap mode="anchored" t5 caption a7 P. aeruginosa E. coli Potentiator Antibiotic ATCC 27853 a PAO1 a MDR 2638 a MDR 3072 a MDR 24530 a ATCC 25922 a None ERY 256 256 512 256 512 32 RIF 32 16 8 16 16 4 VAN >1024 >1024 512 >1024 1024 128 F127-DG 2 ERY 64(0.38) 128(0.53) 64(0.25) 128(0.63) 256(0.53) 16(0.75) RIF 8(0.31) 8(0.56) 4(0.53) 8(0.56) 8(0.53) 4(1.25) VAN 32(0.16) 64(0.19) 64(0.19) 64(0.19) 128(0.25) 128(1.25) Open in a separate window a Inhibitory concentrations for antibiotics are given in μg mL −1 , followed by FICIs given in parentheses.

Techniques: Permeability, Binding Assay, Fluorescence, Positive Control, Staining, Polymer

Journal: Chemical communications (Cambridge, England)

Article Title: Desferrioxamine:gallium-pluronic micelles increase outer membrane permeability and potentiate antibiotic activity against Pseudomonas aeruginosa †

doi: 10.1039/c8cc08134d

Figure Lengend Snippet: Antimicrobial activity of F127-DG 2 or F127 + DG combined with selected antibiotics against P. aeruginosa and E. coli . The MIC of F127-DG 2 alone or free DG was greater than 1024 µM for all strains. FICI o 0.25 considered high synergistic activity, 0.25 o FICI o 0.75 considered moderate synergistic activity, and FICI > 0.75 considered no synergistic activity

Article Snippet: Neither F127-DG 2 nor F127 plus DG potentiated antibiotic activity against E. coli due to lack of the necessary OM receptors for DG. table ft1 table-wrap mode="anchored" t5 caption a7 P. aeruginosa E. coli Potentiator Antibiotic ATCC 27853 a PAO1 a MDR 2638 a MDR 3072 a MDR 24530 a ATCC 25922 a None ERY 256 256 512 256 512 32 RIF 32 16 8 16 16 4 VAN >1024 >1024 512 >1024 1024 128 F127-DG 2 ERY 64(0.38) 128(0.53) 64(0.25) 128(0.63) 256(0.53) 16(0.75) RIF 8(0.31) 8(0.56) 4(0.53) 8(0.56) 8(0.53) 4(1.25) VAN 32(0.16) 64(0.19) 64(0.19) 64(0.19) 128(0.25) 128(1.25) Open in a separate window a Inhibitory concentrations for antibiotics are given in μg mL −1 , followed by FICIs given in parentheses.

Techniques: Activity Assay

Journal: Chemical communications (Cambridge, England)

Article Title: Desferrioxamine:gallium-pluronic micelles increase outer membrane permeability and potentiate antibiotic activity against Pseudomonas aeruginosa †

doi: 10.1039/c8cc08134d

Figure Lengend Snippet: Survival of P. aeruginosa cells treated for 4 h shows bacteriostatic activity for ERY when combined with F127-DG2, while RIF and VAN combinations were bactericidal. (A) MHA plates at 0 and 4 hour for cultures of P. aeruginosa treated with F127-DG2 combined with ERY, RIF, or VAN. (A) F127-DG2 combined with ERY is bacteriostatic against P. aeruginosa whereas RIF or VAN are bactericidal. Unmodified F127 + DG combined with tested antibiotics did not result in inhibitory activity against P. aeruginosa and E. coli was also relatively unaffected by either formulation. Note: 128 µM F127-DG2 (or 128 µM F127+ 256 µM DG) and 96 µg mL−1 ERY, 12 µg mL−1 RIF, or 48 µg mL−1 were used against P. aeruginosa. One-way ANOVA performed for P. aeruginosa with F127-DG2 plus antibiotics relative to t = 0 h positive control, ***p < 0.001.

Article Snippet: Neither F127-DG 2 nor F127 plus DG potentiated antibiotic activity against E. coli due to lack of the necessary OM receptors for DG. table ft1 table-wrap mode="anchored" t5 caption a7 P. aeruginosa E. coli Potentiator Antibiotic ATCC 27853 a PAO1 a MDR 2638 a MDR 3072 a MDR 24530 a ATCC 25922 a None ERY 256 256 512 256 512 32 RIF 32 16 8 16 16 4 VAN >1024 >1024 512 >1024 1024 128 F127-DG 2 ERY 64(0.38) 128(0.53) 64(0.25) 128(0.63) 256(0.53) 16(0.75) RIF 8(0.31) 8(0.56) 4(0.53) 8(0.56) 8(0.53) 4(1.25) VAN 32(0.16) 64(0.19) 64(0.19) 64(0.19) 128(0.25) 128(1.25) Open in a separate window a Inhibitory concentrations for antibiotics are given in μg mL −1 , followed by FICIs given in parentheses.

Techniques: Activity Assay, Formulation, Positive Control

Journal: Toxicology and applied pharmacology

Article Title: Embryoid body test with morphological and molecular endpoints implicates potential developmental toxicity of trans -resveratrol

doi: 10.1016/j.taap.2018.07.006

Figure Lengend Snippet: Chemicals used for the present study

Article Snippet: The preparation of cis -resveratrol may contain 1–5% of trans -resveratrol, according to the product information of the supplier ( www.caymanchem.com/product/10004235 ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 1. caption a7 The chemical structures of the compounds evaluated in the present study (A), and the experimental scheme to assess the morphogenetic and molecular impact of compound exposures using P19C5 embryoid bodies (B). table ft1 table-wrap mode="anchored" t5 Table 1. caption a7 Compound Name CASRN Vendor (catalog number) Stock concentration *1 Figures *2 trans -Resveratrol 501-36-0 Selleck (L2900; Anti-diabetes Compound Library) 10 mM Santa Cruz (200808) 50 mM , , Cayman (70675) 10 mM , cis -Resveratrol 61434-67-1 Cayman (10004235) 10 mM , Resveratrol-3-O-sulfate 858127-11-4 Cayman (14942) 10 mM , Resve ratrol-3-O-D-glucuronide 387372-17-0 Cayman (13832) 10 mM , Resveratrol-4’-O-D-glucuronide 387372-20-5 Cayman (13833) 10 mM , Diethylstilbestrol 56-53-1 Santa Cruz (204720) 50 mM Raloxifene 82640-04-8 Santa Cruz (204230) 50 mM SRT1720 925434-55-5 Sigma-Aldrich (567860) 10 mM EX527 49843-98-3 Sigma-Aldrich (E7034) 50 mM Aphidicolin 38966-21-1 Cayman (14007) 1 mM , Hydroxyurea 127-07-1 Sigma-Aldrich (H8627) 100 mM , Open in a separate window CASRN, Chemical Abstracts Service Registry Number *1 All compounds are dissolved in dimethyl sulfoxide (DMSO), except for hydroxyurea (dissolved in H2O) *2 Figure numbers that show experimental data using the corresponding chemical stocks Chemicals used for the present study 2.2.

Techniques: Concentration Assay, Drug discovery, Two-Dimensional Gel Electrophoresis

Journal: Analytical and bioanalytical chemistry

Article Title: Toward miniaturized analysis of chemical identity and purity of radiopharmaceuticals via microchip electrophoresis

doi: 10.1007/s00216-018-0924-y

Figure Lengend Snippet: Limits of detection (LODs) and quantitation (LOQs) for all setups for FLT and its impurities. Blank entries indicate conditions that were not measured. By combining a higher performance light source and detector with 500 μm OPL (bold entries), the sensitivity of the MCE setup was comparable to HPLC (bold entries).

Article Snippet: The values were also significantly worse than those previously measured in a commercial CE system (5 – 11 μM; Beckman Coulter PA800) [ 32 ], likely due to differences in the optical system, capillary environment (i.e. temperature-controlled in the commercial CE system), and signal processing. table ft1 table-wrap mode="anchored" t5 Table 1. caption a7 Experimental Setup Compound Thymidine Thymine FA Stavudine FLT CLT K222 MCE detection chip ( with 500μm OPL) Wavelength (nm) 256 256 224 256 256 256 Detector 1 (lower performance) LOD 8 30 LOQ 30 96 Detector 2 (higher performance) LOD 2 3 7 3 2 3 LOQ 8 10 23 10 8 9 In-capillary detection Wavelength (nm) 256 256 224 256 256 256 Detector 1 (lower performance) LOD (μM) 210 260 790 310 300 1100 LOQ (μM) 750 850 2600 1000 1000 3500 Detector 2 (higher performance) LOD (μM) 22 21 54 27 25 75 LOQ (μM) 72 69 180 91 84 250 HPLC Wavelength (nm) 224 254 254 * * LOD (μM) 35 2 2 Not detected LOQ (μM) 116 4 5 Not detected Commercial CE Wavelength (nm) 254 254 218 254 254 254 218 205 LOD (μM) 5 5 11 7 6 6 180 120 LOQ (μM) 13 14 36 15 20 15 570 390 Open in a separate window * Measurements were attempted at various wavelengths (205, 218, 224, 236, 254, and 267 nm) but K222 could not be detected Limits of detection (LODs) and quantitation (LOQs) for all setups for FLT and its impurities.

Techniques: Quantitation Assay, Chromatin Immunoprecipitation

Journal: Analytical and bioanalytical chemistry

Article Title: Toward miniaturized analysis of chemical identity and purity of radiopharmaceuticals via microchip electrophoresis

doi: 10.1007/s00216-018-0924-y

Figure Lengend Snippet: Separation performance. (A) Electropherogram from separation in a capillary-only (0-junction) setup. Peaks: 6 mM thymidine (peak 1), 3 mM thymine (peak 2), 5 mM furfuryl alcohol (peak 3), 6 mM stavudine (peak 4), 3 mM FLT (peak 5), 3 mM CLT (peak 6). (B) Electropherogram from separation in a 1-junction setup (i.e., injection chip with a capillary). Peaks: 5 mM thymidine (peak 1), 2 mM thymine (peak 2), 2.5 mM furfuryl alcohol (peak 3), 5 mM stavudine (peak 4), 2.6 mM FLT (peak 5), and 1.4 mM CLT (peak 6). (C) Electropherogram of sample mixture injected, separated, and detected with the hybrid MCE device (i.e. with 2 capillary-chip junctions). Peaks: 5 mM thymidine (peak 1), 2 mM thymine (peak 2), 2.5 mM furfuryl alcohol (peak 3), 5 mM stavudine (peak 4), 2.6 mM FLT (peak 5), and 1.4 mM CLT (peak 6).

Article Snippet: The values were also significantly worse than those previously measured in a commercial CE system (5 – 11 μM; Beckman Coulter PA800) [ 32 ], likely due to differences in the optical system, capillary environment (i.e. temperature-controlled in the commercial CE system), and signal processing. table ft1 table-wrap mode="anchored" t5 Table 1. caption a7 Experimental Setup Compound Thymidine Thymine FA Stavudine FLT CLT K222 MCE detection chip ( with 500μm OPL) Wavelength (nm) 256 256 224 256 256 256 Detector 1 (lower performance) LOD 8 30 LOQ 30 96 Detector 2 (higher performance) LOD 2 3 7 3 2 3 LOQ 8 10 23 10 8 9 In-capillary detection Wavelength (nm) 256 256 224 256 256 256 Detector 1 (lower performance) LOD (μM) 210 260 790 310 300 1100 LOQ (μM) 750 850 2600 1000 1000 3500 Detector 2 (higher performance) LOD (μM) 22 21 54 27 25 75 LOQ (μM) 72 69 180 91 84 250 HPLC Wavelength (nm) 224 254 254 * * LOD (μM) 35 2 2 Not detected LOQ (μM) 116 4 5 Not detected Commercial CE Wavelength (nm) 254 254 218 254 254 254 218 205 LOD (μM) 5 5 11 7 6 6 180 120 LOQ (μM) 13 14 36 15 20 15 570 390 Open in a separate window * Measurements were attempted at various wavelengths (205, 218, 224, 236, 254, and 267 nm) but K222 could not be detected Limits of detection (LODs) and quantitation (LOQs) for all setups for FLT and its impurities.

Techniques: Injection

Journal: Analytical and bioanalytical chemistry

Article Title: Toward miniaturized analysis of chemical identity and purity of radiopharmaceuticals via microchip electrophoresis

doi: 10.1007/s00216-018-0924-y

Figure Lengend Snippet: Separation performance for the CE setups with different numbers capillary-chip junctions. Migration time (t m ), peak full width at half maximum (w 1/2 ), number of theoretical plates (N), plate height (H), injection component of plate height (H inj ), and detection component of plate height (H det ) are shown for each. Values were calculated for the fastest and slowest eluting analytes, i.e. stavudine and CLT for 1- and 2-junction cases and for thymidine and CLT for the 0-junction case.

Article Snippet: The values were also significantly worse than those previously measured in a commercial CE system (5 – 11 μM; Beckman Coulter PA800) [ 32 ], likely due to differences in the optical system, capillary environment (i.e. temperature-controlled in the commercial CE system), and signal processing. table ft1 table-wrap mode="anchored" t5 Table 1. caption a7 Experimental Setup Compound Thymidine Thymine FA Stavudine FLT CLT K222 MCE detection chip ( with 500μm OPL) Wavelength (nm) 256 256 224 256 256 256 Detector 1 (lower performance) LOD 8 30 LOQ 30 96 Detector 2 (higher performance) LOD 2 3 7 3 2 3 LOQ 8 10 23 10 8 9 In-capillary detection Wavelength (nm) 256 256 224 256 256 256 Detector 1 (lower performance) LOD (μM) 210 260 790 310 300 1100 LOQ (μM) 750 850 2600 1000 1000 3500 Detector 2 (higher performance) LOD (μM) 22 21 54 27 25 75 LOQ (μM) 72 69 180 91 84 250 HPLC Wavelength (nm) 224 254 254 * * LOD (μM) 35 2 2 Not detected LOQ (μM) 116 4 5 Not detected Commercial CE Wavelength (nm) 254 254 218 254 254 254 218 205 LOD (μM) 5 5 11 7 6 6 180 120 LOQ (μM) 13 14 36 15 20 15 570 390 Open in a separate window * Measurements were attempted at various wavelengths (205, 218, 224, 236, 254, and 267 nm) but K222 could not be detected Limits of detection (LODs) and quantitation (LOQs) for all setups for FLT and its impurities.

Techniques: Migration, Injection