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N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation

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...

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Autores principales: Lavrenov, Sergey N., Isakova, Elena B., Panov, Alexey A., Simonov, Alexander Y., Tatarskiy, Viktor V., Trenin, Alexey S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765952/
https://www.ncbi.nlm.nih.gov/pubmed/33339219
http://dx.doi.org/10.3390/ph13120469
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author Lavrenov, Sergey N.
Isakova, Elena B.
Panov, Alexey A.
Simonov, Alexander Y.
Tatarskiy, Viktor V.
Trenin, Alexey S.
author_facet Lavrenov, Sergey N.
Isakova, Elena B.
Panov, Alexey A.
Simonov, Alexander Y.
Tatarskiy, Viktor V.
Trenin, Alexey S.
author_sort Lavrenov, Sergey N.
collection PubMed
description 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.
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spelling pubmed-77659522020-12-28 N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation Lavrenov, Sergey N. Isakova, Elena B. Panov, Alexey A. Simonov, Alexander Y. Tatarskiy, Viktor V. Trenin, Alexey S. Pharmaceuticals (Basel) Article 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. MDPI 2020-12-16 /pmc/articles/PMC7765952/ /pubmed/33339219 http://dx.doi.org/10.3390/ph13120469 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lavrenov, Sergey N.
Isakova, Elena B.
Panov, Alexey A.
Simonov, Alexander Y.
Tatarskiy, Viktor V.
Trenin, Alexey S.
N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation
title N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation
title_full N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation
title_fullStr N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation
title_full_unstemmed N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation
title_short N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation
title_sort n-(hydroxyalkyl) derivatives of tris(1h-indol-3-yl)methylium salts as promising antibacterial agents: synthesis and biological evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765952/
https://www.ncbi.nlm.nih.gov/pubmed/33339219
http://dx.doi.org/10.3390/ph13120469
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