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Keywords = tris(1H-indol-3-yl)methylium

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13 pages, 436 KB  
Article
Evaluation of New Antimicrobial Agents Based on tris(1H-Indol-3-yl)methylium Salts: Activity, Toxicity, Suppression of Experimental Sepsis in Mice
by Alexey S. Trenin, Elena B. Isakova, Michael I. Treshchalin, Vasilisa A. Polozkova, Elena P. Mirchink, Alexey A. Panov, Alexander Y. Simonov, Olga P. Bychkova, Victor V. Tatarskiy and Sergey N. Lavrenov
Pharmaceuticals 2022, 15(2), 118; https://doi.org/10.3390/ph15020118 - 19 Jan 2022
Cited by 5 | Viewed by 3058
Abstract
The antimicrobial activity and toxicity of three novel synthetic antibacterial agents containing tris(1H-indol-3-yl)methylium fragment were studied in vitro and in vivo. All compounds in vitro revealed high activity (minimal inhibitory concentration (MIC) 0.13–1.0 µg/mL) against bacteria that were either sensitive [...] Read more.
The antimicrobial activity and toxicity of three novel synthetic antibacterial agents containing tris(1H-indol-3-yl)methylium fragment were studied in vitro and in vivo. All compounds in vitro revealed high activity (minimal inhibitory concentration (MIC) 0.13–1.0 µg/mL) against bacteria that were either sensitive or resistant to antibiotics, including multidrug-resistant clinical isolates. The derivatives combining high antimicrobial activity with relatively low cytotoxicity against human donor fibroblasts HPF-hTERT were subjected to further testing on mice. In vivo they revealed fairly good tolerance and relatively low toxicity. Acute toxicity was evaluated, and the main indicators of toxicity, including LD50 and LD10, were determined. A study of compounds in vivo showed their efficiency in the model of staphylococcal sepsis in mice. The efficiency of compounds may be due to the ability of indolylmethylium salts to form pores in the cytoplasmic membrane of microbial cells and thereby facilitate the penetration of molecules into the pathogen. Full article
(This article belongs to the Special Issue Small Molecules as Antimicrobials)
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13 pages, 561 KB  
Article
N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation
by Sergey N. Lavrenov, Elena B. Isakova, Alexey A. Panov, Alexander Y. Simonov, Viktor V. Tatarskiy and Alexey S. Trenin
Pharmaceuticals 2020, 13(12), 469; https://doi.org/10.3390/ph13120469 - 16 Dec 2020
Cited by 10 | Viewed by 2830
Abstract
The wide spread of pathogens resistance requires the development of new antimicrobial agents capable of overcoming drug resistance. The main objective of the study is to elucidate the effect of substitutions in tris(1H-indol-3-yl)methylium derivatives on their antibacterial activity and toxicity [...] Read more.
The wide spread of pathogens resistance requires the development of new antimicrobial agents capable of overcoming drug resistance. The main objective of the study is to elucidate the effect of substitutions in tris(1H-indol-3-yl)methylium derivatives on their antibacterial activity and toxicity to human cells. A series of new compounds were synthesized and tested. Their antibacterial activity in vitro was performed on 12 bacterial strains, including drug resistant strains, that were clinical isolates or collection strains. The cytotoxic effect of the compounds was determined using an test with HPF-hTERT (human postnatal fibroblasts, immortalized with hTERT) cells. The activity of the obtained compounds depended on the carbon chain length. Derivatives with C5–C6 chains were more active. The minimum inhibitory concentration (MIC) of the most active compound on Gram-positive bacteria, including MRSA, was 0.5 μg/mL. Compounds with C5–C6 chains also revealed high activity against Staphylococcus epidermidis (1.0 and 0.5 μg/mL, respectively) and moderate activity against Gram-negative bacteria Escherichia coli (8 μg/mL) and Klebsiella pneumonia (2 and 8 μg/mL, respectively). However, they have no activity against Salmonella cholerasuis and Pseudomonas aeruginosa. The most active compounds revealed higher antibacterial activity on MRSA than the reference drug levofloxacin, and their ratio between antibacterial and cytotoxic activity exceeded 10 times. The data obtained provide a basis for further study of this promising group of substances. Full article
(This article belongs to the Special Issue Novel Antibacterial Agents)
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14 pages, 1163 KB  
Article
Isolation and Antibacterial Activity of Indole Alkaloids from Pseudomonas aeruginosa UWI-1
by Antonio Ramkissoon, Mohindra Seepersaud, Anderson Maxwell, Jayaraj Jayaraman and Adesh Ramsubhag
Molecules 2020, 25(16), 3744; https://doi.org/10.3390/molecules25163744 - 17 Aug 2020
Cited by 31 | Viewed by 5511
Abstract
In this study, we report the first isolation of three antibiotic indole alkaloid compounds from a Pseudomonad bacterium, Pseudomonas aeruginosa UWI-1. The bacterium was batch fermented in a modified Luria Broth medium and compounds were solvent extracted and isolated by bioassay-guided fractionation. The [...] Read more.
In this study, we report the first isolation of three antibiotic indole alkaloid compounds from a Pseudomonad bacterium, Pseudomonas aeruginosa UWI-1. The bacterium was batch fermented in a modified Luria Broth medium and compounds were solvent extracted and isolated by bioassay-guided fractionation. The three compounds were identified as (1) tris(1H-indol-3-yl) methylium, (2) bis(indol-3-yl) phenylmethane, and (3) indolo (2, 1b) quinazoline-6, 12 dione. A combination of 1D and 2D NMR, high-resolution mass spectrometry data and comparison from related data from the literature was used to determine the chemical structures of the compounds. Compounds 1–3 were evaluated in vitro for their antimicrobial activities against a wide range of microorganisms using the broth microdilution technique. Compounds 1 and 2 displayed antibacterial activity against only Gram-positive pathogens, although 1 had significantly lower minimum inhibitory concentration (MIC) values than 2. Compound 3 displayed potent broad-spectrum antimicrobial activity against a range of Gram positive and negative bacteria. Several genes identified from the genome of P. aeruginosa UWI-1 were postulated to contribute to the biosynthesis of these compounds and we attempted to outline a possible route for bacterial synthesis. This study demonstrated the extended metabolic capability of Pseudomonas aeruginosa in synthesizing new chemotypes of bioactive compounds. Full article
(This article belongs to the Special Issue Microbial Natural Products)
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