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: RSC Medicinal Chemistry

Article Title: Potent trifluoromethoxy, trifluoromethylsulfonyl, trifluoromethylthio and pentafluorosulfanyl containing (1,3,4-oxadiazol-2-yl)benzamides against drug-resistant Gram-positive bacteria † †Electronic supplementary information (ESI) available: Synthesis and characterization data of compounds ( 1 H, 13 C NMR and HRMS). Bacterial strains, media, cell lines and reagents used. Protocols for the determination of the MICs and MBCs against bacteria, synergy of compounds with standard antibiotics, in vitro cytotoxicity analysis of compounds 6 , 11 , 12 and 13 against human colorectal and murine macrophage cells, hemolysis assay, time-kill kinetics analysis, intracellular infection of J774 cells with MRSA and treatment with compounds 6 and 12 . Table of bacterial isolates used in this study. See DOI: 10.1039/c9md00391f

doi: 10.1039/c9md00391f

Figure Lengend Snippet: Initial screening (MIC, in μg mL –1 ) of (1,3,4-oxadiazol-2-yl)benzamides against Staphylococcus aureus ATCC 25923 and methicillin-resistant Staphylococcus aureus (MRSA) ATCC 33592

Article Snippet: Unfortunately, this series was not as active as our original hit molecules (compare MICs for 5 , 6 , 11 , 12 , and 13 , , with compounds 14–17 , ), demonstrating that the phenyl group is needed for optimal antibacterial activity. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window caption a7 caption a8 Trifluoromethyl-substituted heteroaromatic compounds synthesized. table ft1 table-wrap mode="anchored" t5 caption a7 Compound S. aureus ATCC 25923 MRSA ATCC 33592 14 4 2 15 64 32 16 16 16 17 >64 >64 Open in a separate window caption a8 Initial screening (MIC, in μg mL –1 ) of other trifluoromethyl-substituted heteroaromatic compounds against Staphylococcus aureus ATCC 25923 and MRSA ATCC 33592 Compounds 6 , 11 , 12 , & 13 are not active against Gram-negative bacteria We next moved to test if compounds 6 , 11 , 12 , and 13 were effective against Gram-negative bacteria.

Techniques:

Journal: RSC Medicinal Chemistry

Article Title: Potent trifluoromethoxy, trifluoromethylsulfonyl, trifluoromethylthio and pentafluorosulfanyl containing (1,3,4-oxadiazol-2-yl)benzamides against drug-resistant Gram-positive bacteria † †Electronic supplementary information (ESI) available: Synthesis and characterization data of compounds ( 1 H, 13 C NMR and HRMS). Bacterial strains, media, cell lines and reagents used. Protocols for the determination of the MICs and MBCs against bacteria, synergy of compounds with standard antibiotics, in vitro cytotoxicity analysis of compounds 6 , 11 , 12 and 13 against human colorectal and murine macrophage cells, hemolysis assay, time-kill kinetics analysis, intracellular infection of J774 cells with MRSA and treatment with compounds 6 and 12 . Table of bacterial isolates used in this study. See DOI: 10.1039/c9md00391f

doi: 10.1039/c9md00391f

Figure Lengend Snippet: Initial screening (MIC, in μg mL –1 ) of other trifluoromethyl-substituted heteroaromatic compounds against Staphylococcus aureus ATCC 25923 and MRSA ATCC 33592

Article Snippet: Unfortunately, this series was not as active as our original hit molecules (compare MICs for 5 , 6 , 11 , 12 , and 13 , , with compounds 14–17 , ), demonstrating that the phenyl group is needed for optimal antibacterial activity. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window caption a7 caption a8 Trifluoromethyl-substituted heteroaromatic compounds synthesized. table ft1 table-wrap mode="anchored" t5 caption a7 Compound S. aureus ATCC 25923 MRSA ATCC 33592 14 4 2 15 64 32 16 16 16 17 >64 >64 Open in a separate window caption a8 Initial screening (MIC, in μg mL –1 ) of other trifluoromethyl-substituted heteroaromatic compounds against Staphylococcus aureus ATCC 25923 and MRSA ATCC 33592 Compounds 6 , 11 , 12 , & 13 are not active against Gram-negative bacteria We next moved to test if compounds 6 , 11 , 12 , and 13 were effective against Gram-negative bacteria.

Techniques:

Journal: RSC Medicinal Chemistry

Article Title: Potent trifluoromethoxy, trifluoromethylsulfonyl, trifluoromethylthio and pentafluorosulfanyl containing (1,3,4-oxadiazol-2-yl)benzamides against drug-resistant Gram-positive bacteria † †Electronic supplementary information (ESI) available: Synthesis and characterization data of compounds ( 1 H, 13 C NMR and HRMS). Bacterial strains, media, cell lines and reagents used. Protocols for the determination of the MICs and MBCs against bacteria, synergy of compounds with standard antibiotics, in vitro cytotoxicity analysis of compounds 6 , 11 , 12 and 13 against human colorectal and murine macrophage cells, hemolysis assay, time-kill kinetics analysis, intracellular infection of J774 cells with MRSA and treatment with compounds 6 and 12 . Table of bacterial isolates used in this study. See DOI: 10.1039/c9md00391f

doi: 10.1039/c9md00391f

Figure Lengend Snippet: The minimum inhibitory concentrations (MICs in μg mL –1 ) of compounds 6 , 11 , 12 and 13 against methicillin-sensitive Staphylococcus aureus , methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA) strains

Article Snippet: Unfortunately, this series was not as active as our original hit molecules (compare MICs for 5 , 6 , 11 , 12 , and 13 , , with compounds 14–17 , ), demonstrating that the phenyl group is needed for optimal antibacterial activity. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window caption a7 caption a8 Trifluoromethyl-substituted heteroaromatic compounds synthesized. table ft1 table-wrap mode="anchored" t5 caption a7 Compound S. aureus ATCC 25923 MRSA ATCC 33592 14 4 2 15 64 32 16 16 16 17 >64 >64 Open in a separate window caption a8 Initial screening (MIC, in μg mL –1 ) of other trifluoromethyl-substituted heteroaromatic compounds against Staphylococcus aureus ATCC 25923 and MRSA ATCC 33592 Compounds 6 , 11 , 12 , & 13 are not active against Gram-negative bacteria We next moved to test if compounds 6 , 11 , 12 , and 13 were effective against Gram-negative bacteria.

Techniques:

Journal: RSC Medicinal Chemistry

Article Title: Potent trifluoromethoxy, trifluoromethylsulfonyl, trifluoromethylthio and pentafluorosulfanyl containing (1,3,4-oxadiazol-2-yl)benzamides against drug-resistant Gram-positive bacteria † †Electronic supplementary information (ESI) available: Synthesis and characterization data of compounds ( 1 H, 13 C NMR and HRMS). Bacterial strains, media, cell lines and reagents used. Protocols for the determination of the MICs and MBCs against bacteria, synergy of compounds with standard antibiotics, in vitro cytotoxicity analysis of compounds 6 , 11 , 12 and 13 against human colorectal and murine macrophage cells, hemolysis assay, time-kill kinetics analysis, intracellular infection of J774 cells with MRSA and treatment with compounds 6 and 12 . Table of bacterial isolates used in this study. See DOI: 10.1039/c9md00391f

doi: 10.1039/c9md00391f

Figure Lengend Snippet: The minimum bactericidal concentration (MBC, in μg mL –1 ) of compounds 6 , 11 , 12 , & 13 and control antibiotics against MRSA ATCC 33592

Article Snippet: Unfortunately, this series was not as active as our original hit molecules (compare MICs for 5 , 6 , 11 , 12 , and 13 , , with compounds 14–17 , ), demonstrating that the phenyl group is needed for optimal antibacterial activity. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window caption a7 caption a8 Trifluoromethyl-substituted heteroaromatic compounds synthesized. table ft1 table-wrap mode="anchored" t5 caption a7 Compound S. aureus ATCC 25923 MRSA ATCC 33592 14 4 2 15 64 32 16 16 16 17 >64 >64 Open in a separate window caption a8 Initial screening (MIC, in μg mL –1 ) of other trifluoromethyl-substituted heteroaromatic compounds against Staphylococcus aureus ATCC 25923 and MRSA ATCC 33592 Compounds 6 , 11 , 12 , & 13 are not active against Gram-negative bacteria We next moved to test if compounds 6 , 11 , 12 , and 13 were effective against Gram-negative bacteria.

Techniques: Concentration Assay, Control

Journal: RSC Medicinal Chemistry

Article Title: Potent trifluoromethoxy, trifluoromethylsulfonyl, trifluoromethylthio and pentafluorosulfanyl containing (1,3,4-oxadiazol-2-yl)benzamides against drug-resistant Gram-positive bacteria † †Electronic supplementary information (ESI) available: Synthesis and characterization data of compounds ( 1 H, 13 C NMR and HRMS). Bacterial strains, media, cell lines and reagents used. Protocols for the determination of the MICs and MBCs against bacteria, synergy of compounds with standard antibiotics, in vitro cytotoxicity analysis of compounds 6 , 11 , 12 and 13 against human colorectal and murine macrophage cells, hemolysis assay, time-kill kinetics analysis, intracellular infection of J774 cells with MRSA and treatment with compounds 6 and 12 . Table of bacterial isolates used in this study. See DOI: 10.1039/c9md00391f

doi: 10.1039/c9md00391f

Figure Lengend Snippet: The cumulative fractional inhibitory concentration index (∑FICI) range of compounds 6 , 11 , 12 , and 13 in combination with antibiotics against MRSA ATCC 33592. ∑FICI was interpreted as follows: ∑FICI of ≤0.5 is considered to demonstrate synergy (SYN). An ∑FICI of >0.5–1.25 was categorized as additive (ADD). ∑FICI of >1.25–4 was considered as indifference (IND), while ∑FICI values of >4 were categorized as antagonistic

Article Snippet: Unfortunately, this series was not as active as our original hit molecules (compare MICs for 5 , 6 , 11 , 12 , and 13 , , with compounds 14–17 , ), demonstrating that the phenyl group is needed for optimal antibacterial activity. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window caption a7 caption a8 Trifluoromethyl-substituted heteroaromatic compounds synthesized. table ft1 table-wrap mode="anchored" t5 caption a7 Compound S. aureus ATCC 25923 MRSA ATCC 33592 14 4 2 15 64 32 16 16 16 17 >64 >64 Open in a separate window caption a8 Initial screening (MIC, in μg mL –1 ) of other trifluoromethyl-substituted heteroaromatic compounds against Staphylococcus aureus ATCC 25923 and MRSA ATCC 33592 Compounds 6 , 11 , 12 , & 13 are not active against Gram-negative bacteria We next moved to test if compounds 6 , 11 , 12 , and 13 were effective against Gram-negative bacteria.

Techniques: Concentration 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: 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