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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Systematic analysis of gut bacterial carcinogen metabolism and its functional consequences
Boyao Zhang ; George-Eugen Maftei ; Bartosz Bartmanski ; Michael Zimmermann ;
Abstract: Organic carcinogens, in particular DNA-reactive compounds, contribute to the irreversible initiation step of tumorigenesis through introduction of genomic instability. Although carcinogen bioactivation and detoxification by human enzymes has been extensively studied, carcinogen biotransformation by human-associated bacteria, the microbiota, has not yet been systematically investigated. We tested the biotransformation of 68 mutagenic carcinogens by 34 bacterial species representative for the upper and lower human gastrointestinal tract and found that the majority (41) of the tested carcinogens undergo bacterial biotransformation. To assess the functional consequences of microbial carcinogen metabolism, we developed a pipeline to couple gut bacterial carcinogen biotransformation assays with Ames mutagenicity testing and liver biotransformation experiments. This revealed a bidirectional crosstalk between gut microbiota and host carcinogen metabolism, which we validated in gnotobiotic mouse models. Overall, the systematic assessment of gut microbiota carcinogen biotransformation and its interplay with host metabolism highlights the gut microbiome as an important modulator of exposome-induced tumorigenesis.
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Purchased from AmBeed: 446-86-6 ; 121-66-4 ; 607-35-2 ; 67-20-9 ; 105650-23-5 ; 59-87-0 ; 117-39-5 ; 57-97-6 ; 5131-60-2 ; 512-56-1 ; 62-44-2 ; 6959-48-4 ; 84-65-1 ; 137-17-7 ; 117-39-5 ; 153-78-6 ; 1614-12-6 ; 298-81-7 ; 404-86-4 ; 320-67-2 ; 99-55-8 ; 94-52-0 ; 2832-40-8 ; 101-61-1 ; 103-33-3 ; 114-83-0 ; 64091-91-4 ; 53-96-3 ; 3817-11-6 ; 90-94-8 ; 613-13-8 ; 56-57-5 ; 91-64-5 ; 26148-68-5 ; 101-80-4 ; 139-65-1 ; 366-70-1 ; 389-08-2 ; 99-59-2 ; 132-32-1 ; 394-69-4 ; 3544-23-8 ; 389-08-2 ; 320-67-2 ; 82-28-0 ; 2475-45-8 ; 129-15-7
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CAS No. : | 512-56-1 |
Formula : | C3H9O4P |
M.W : | 140.07 |
SMILES Code : | O=P(OC)(OC)OC |
MDL No. : | MFCD00008348 |
InChI Key : | WVLBCYQITXONBZ-UHFFFAOYSA-N |
Pubchem ID : | 10541 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H302-H315-H319-H340-H351 |
Precautionary Statements: | P301+P330+P331-P312-P302+P352-P337+P313-P201-P280 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate; In 1,4-dioxane; at 90℃; for 6.0h;Inert atmosphere; | Compound IV (260 mg, 0.93 mmol) was dissolved in dioxane (5 ml).Trimethylphosphate (650 mg, 4.6 mmol) and K2CO3 (192 mg, 1.39 mmol) were added, and the reaction mixture was stirred under 2 at 90 C for 6hr until the starting material was consumed. The reaction mixture was diluted with water and extracted with EtOAc. The solvent was removed, and the residue was purified by silica gel column chromatography (PE: EtOAc=l : l) to give intermediate B as a white solid (270 mg, 86 %). ¾ NMR (CDCI3) delta: 7.7 (s, 1H), 4.34 (m, 1H), 4.25 (m, 1H), 3.33 (s, 3H), 2.1-1.6 (m, 10H) and 0.86 ppm (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In acetonitrile; at 80℃; for 24h;Inert atmosphere; | General procedure: 1,2-Dimethyl imidazole (9.61 g; 0.10 mol) and trimethylphosphate (14.01 g; 0.10 mol) were mixed at room temperature under argon and vigorous stirring, then heated to 80°C and stirred at this temperature for 1h. Acetonitrile (20 mL) was added and the mixture was stirred at 80°C for 23h. The mixture was left at room temperature, the precipitate was separated,washed twice with acetonitrile and dried under vacuum (2 Torr) for 4 h at 80°C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With potassium carbonate; In N,N-dimethyl-formamide; at 220℃; for 0.5h; | General procedure: A mixture of 4-oxo-1,4-dihydroquinoline-2-carboxylic acid alkylester (1, 1 mmol), base (1.3 mmol), the corresponding alkylatingagent (alkyl iodide, 1.5 mmol; others, 1.2 mmol) and anhydrousDMF (5 mL) was stirred at the appropriate temperature andmonitored by TLC (DCM:MeOH 4.7:0.3). After a specified time(Table 2), the mixture was carefully poured into ice-water. Thecompounds obtained were isolated and purified as was indicatedabove. Alkylating agents, bases and solvents are presented inTable 2. |