Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Structure of IMB-T130 (5-chloro-N-[4-(pyridin-2-yl)-1, 3-thiazol-2-yl] thiophene-2-carboxamide).

Article Snippet: Next, the chip was exposed to different concentrations of IMB-T130, and the response units for five different concentrations (1.875–30 μM) of IMB-T130 were measured by SPR (BIAcore X100 instrument, GE Healthcare).

Techniques:

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Inhibition of DHQS by IMB-T130. DHQS (1 μg/mL) was incubated with 0.15–20 μg/mL of IMB-T130 at room temperature for 30 min and the catalytic activity was determined (see Methods section). The IC 50 value is plotted as the inhibition ratio of the OD 630 over the compound concentration (log plot) that fits a variable-slope dose-response equation. The experiment was repeated three times.

Article Snippet: Next, the chip was exposed to different concentrations of IMB-T130, and the response units for five different concentrations (1.875–30 μM) of IMB-T130 were measured by SPR (BIAcore X100 instrument, GE Healthcare).

Techniques: Inhibition, Incubation, Activity Assay, Concentration Assay

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: SPR results for the interaction between DHQS and IMB-T130. A sensor chip coated with purified protein was exposed to 1.875–30 μM of IMB-T130. The change in response units is shown.

Article Snippet: Next, the chip was exposed to different concentrations of IMB-T130, and the response units for five different concentrations (1.875–30 μM) of IMB-T130 were measured by SPR (BIAcore X100 instrument, GE Healthcare).

Techniques: Purification

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Molecular docking for DHQS and IMB-T130. ( a ) Overview of the active pocket of DHQS bound to IMB-T130. IMB-T130 is represented by a stick model (grey, carbon atoms; blue, nitrogen atoms; red, oxygen atoms; yellow, sulfur atoms; green, chlorine atoms). Red sticks represent the amino acid residues interacting with IMB-T130. ( b ) A carbonyl oxygen atom forms a conventional hydrogen bond with Asn154 and Lys323 (green line). A carbon-hydrogen bond formed between the carbonyl group of Asn246 and pyridine (grey line). Thiazole and pyridine formed different hydrophobic interactions with Lys144, Asn246, and His249 (purple and orange lines).

Article Snippet: Next, the chip was exposed to different concentrations of IMB-T130, and the response units for five different concentrations (1.875–30 μM) of IMB-T130 were measured by SPR (BIAcore X100 instrument, GE Healthcare).

Techniques:

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Mean blood concentration profiles of IMB-T130 following oral (p.o) and iv doses of 20 and 5 mg/kg in in male Sprague Dawley rats. Pharmacokinetic parameters were determined after the administration of the oral and iv dose to rats. T max , time to reach C max ; C max , maximum plasma concentration; t (1/2) , half-life; AUC, area under the concentration curve; V ss , volume of distribution at steady state.

Article Snippet: Next, the chip was exposed to different concentrations of IMB-T130, and the response units for five different concentrations (1.875–30 μM) of IMB-T130 were measured by SPR (BIAcore X100 instrument, GE Healthcare).

Techniques: Concentration Assay

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Antibacterial activity of IMB-T130 against the M. smegmatis strains with a vector control or overexpressing plasmid for Mt DHQS and Mt L12 genes.

Article Snippet: Next, the chip was exposed to different concentrations of IMB-T130, and the response units for five different concentrations (1.875–30 μM) of IMB-T130 were measured by SPR (BIAcore X100 instrument, GE Healthcare).

Techniques: Activity Assay, Plasmid Preparation

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Intracellular anti-TB activity of IMB-T130.

Article Snippet: Next, the chip was exposed to different concentrations of IMB-T130, and the response units for five different concentrations (1.875–30 μM) of IMB-T130 were measured by SPR (BIAcore X100 instrument, GE Healthcare).

Techniques: Activity Assay

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Structure of IMB-T130 (5-chloro-N-[4-(pyridin-2-yl)-1, 3-thiazol-2-yl] thiophene-2-carboxamide).

Article Snippet: Compound IMB-T130 was purchased from J&K Chemical (China; synthesized by Enamine Ltd., Ukraine).

Techniques:

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Inhibition of DHQS by IMB-T130. DHQS (1 μg/mL) was incubated with 0.15–20 μg/mL of IMB-T130 at room temperature for 30 min and the catalytic activity was determined (see Methods section). The IC 50 value is plotted as the inhibition ratio of the OD 630 over the compound concentration (log plot) that fits a variable-slope dose-response equation. The experiment was repeated three times.

Article Snippet: Compound IMB-T130 was purchased from J&K Chemical (China; synthesized by Enamine Ltd., Ukraine).

Techniques: Inhibition, Incubation, Activity Assay, Concentration Assay

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: SPR results for the interaction between DHQS and IMB-T130. A sensor chip coated with purified protein was exposed to 1.875–30 μM of IMB-T130. The change in response units is shown.

Article Snippet: Compound IMB-T130 was purchased from J&K Chemical (China; synthesized by Enamine Ltd., Ukraine).

Techniques: Purification

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Molecular docking for DHQS and IMB-T130. ( a ) Overview of the active pocket of DHQS bound to IMB-T130. IMB-T130 is represented by a stick model (grey, carbon atoms; blue, nitrogen atoms; red, oxygen atoms; yellow, sulfur atoms; green, chlorine atoms). Red sticks represent the amino acid residues interacting with IMB-T130. ( b ) A carbonyl oxygen atom forms a conventional hydrogen bond with Asn154 and Lys323 (green line). A carbon-hydrogen bond formed between the carbonyl group of Asn246 and pyridine (grey line). Thiazole and pyridine formed different hydrophobic interactions with Lys144, Asn246, and His249 (purple and orange lines).

Article Snippet: Compound IMB-T130 was purchased from J&K Chemical (China; synthesized by Enamine Ltd., Ukraine).

Techniques:

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Mean blood concentration profiles of IMB-T130 following oral (p.o) and iv doses of 20 and 5 mg/kg in in male Sprague Dawley rats. Pharmacokinetic parameters were determined after the administration of the oral and iv dose to rats. T max , time to reach C max ; C max , maximum plasma concentration; t (1/2) , half-life; AUC, area under the concentration curve; V ss , volume of distribution at steady state.

Article Snippet: Compound IMB-T130 was purchased from J&K Chemical (China; synthesized by Enamine Ltd., Ukraine).

Techniques: Concentration Assay

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Antibacterial activity of IMB-T130 against the M. smegmatis strains with a vector control or overexpressing plasmid for Mt DHQS and Mt L12 genes.

Article Snippet: Compound IMB-T130 was purchased from J&K Chemical (China; synthesized by Enamine Ltd., Ukraine).

Techniques: Activity Assay, Plasmid Preparation

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Intracellular anti-TB activity of IMB-T130.

Article Snippet: Compound IMB-T130 was purchased from J&K Chemical (China; synthesized by Enamine Ltd., Ukraine).

Techniques: Activity Assay

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Structure of IMB-T130 (5-chloro-N-[4-(pyridin-2-yl)-1, 3-thiazol-2-yl] thiophene-2-carboxamide).

Article Snippet: The IMB-T130 plasma concentration was determined by liquid chromatography-mass spectrometry using an ACQUITY UPLC BEH C18 column (Waters; 1.7 µm, 2.1 × 50 mm) .

Techniques:

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Inhibition of DHQS by IMB-T130. DHQS (1 μg/mL) was incubated with 0.15–20 μg/mL of IMB-T130 at room temperature for 30 min and the catalytic activity was determined (see Methods section). The IC 50 value is plotted as the inhibition ratio of the OD 630 over the compound concentration (log plot) that fits a variable-slope dose-response equation. The experiment was repeated three times.

Article Snippet: The IMB-T130 plasma concentration was determined by liquid chromatography-mass spectrometry using an ACQUITY UPLC BEH C18 column (Waters; 1.7 µm, 2.1 × 50 mm) .

Techniques: Inhibition, Incubation, Activity Assay, Concentration Assay

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: SPR results for the interaction between DHQS and IMB-T130. A sensor chip coated with purified protein was exposed to 1.875–30 μM of IMB-T130. The change in response units is shown.

Article Snippet: The IMB-T130 plasma concentration was determined by liquid chromatography-mass spectrometry using an ACQUITY UPLC BEH C18 column (Waters; 1.7 µm, 2.1 × 50 mm) .

Techniques: Purification

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Molecular docking for DHQS and IMB-T130. ( a ) Overview of the active pocket of DHQS bound to IMB-T130. IMB-T130 is represented by a stick model (grey, carbon atoms; blue, nitrogen atoms; red, oxygen atoms; yellow, sulfur atoms; green, chlorine atoms). Red sticks represent the amino acid residues interacting with IMB-T130. ( b ) A carbonyl oxygen atom forms a conventional hydrogen bond with Asn154 and Lys323 (green line). A carbon-hydrogen bond formed between the carbonyl group of Asn246 and pyridine (grey line). Thiazole and pyridine formed different hydrophobic interactions with Lys144, Asn246, and His249 (purple and orange lines).

Article Snippet: The IMB-T130 plasma concentration was determined by liquid chromatography-mass spectrometry using an ACQUITY UPLC BEH C18 column (Waters; 1.7 µm, 2.1 × 50 mm) .

Techniques:

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Mean blood concentration profiles of IMB-T130 following oral (p.o) and iv doses of 20 and 5 mg/kg in in male Sprague Dawley rats. Pharmacokinetic parameters were determined after the administration of the oral and iv dose to rats. T max , time to reach C max ; C max , maximum plasma concentration; t (1/2) , half-life; AUC, area under the concentration curve; V ss , volume of distribution at steady state.

Article Snippet: The IMB-T130 plasma concentration was determined by liquid chromatography-mass spectrometry using an ACQUITY UPLC BEH C18 column (Waters; 1.7 µm, 2.1 × 50 mm) .

Techniques: Concentration Assay

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Antibacterial activity of IMB-T130 against the M. smegmatis strains with a vector control or overexpressing plasmid for Mt DHQS and Mt L12 genes.

Article Snippet: The IMB-T130 plasma concentration was determined by liquid chromatography-mass spectrometry using an ACQUITY UPLC BEH C18 column (Waters; 1.7 µm, 2.1 × 50 mm) .

Techniques: Activity Assay, Plasmid Preparation

Journal: Scientific Reports

Article Title: IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis

doi: 10.1038/s41598-018-35701-z

Figure Lengend Snippet: Intracellular anti-TB activity of IMB-T130.

Article Snippet: The IMB-T130 plasma concentration was determined by liquid chromatography-mass spectrometry using an ACQUITY UPLC BEH C18 column (Waters; 1.7 µm, 2.1 × 50 mm) .

Techniques: Activity Assay