<i>N</i>-(Hydroxyalkyl) Derivatives of <i>tris</i>(1<i>H</i>-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 <i>tris</i>(1<i>H</i>-indol-3-yl)methylium derivatives on their a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/12/469 |
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| author | Sergey N. Lavrenov Elena B. Isakova Alexey A. Panov Alexander Y. Simonov Viktor V. Tatarskiy Alexey S. Trenin |
| author_facet | Sergey N. Lavrenov Elena B. Isakova Alexey A. Panov Alexander Y. Simonov Viktor V. Tatarskiy Alexey S. Trenin |
| author_sort | Sergey N. Lavrenov |
| collection | DOAJ |
| 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 <i>tris</i>(1<i>H</i>-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 <i>Staphylococcus epidermidis</i> (1.0 and 0.5 μg/mL, respectively) and moderate activity against Gram-negative bacteria <i>Escherichia coli</i> (8 μg/mL) and <i>Klebsiella pneumonia</i> (2 and 8 μg/mL, respectively). However, they have no activity against <i>Salmonella cholerasuis</i> and <i>Pseudomonas aeruginosa</i>. 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. |
| first_indexed | 2024-03-10T14:02:19Z |
| format | Article |
| id | doaj.art-badb3b80ee774653b183ae99de2d512d |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T14:02:19Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-badb3b80ee774653b183ae99de2d512d2023-11-21T01:02:22ZengMDPI AGPharmaceuticals1424-82472020-12-01131246910.3390/ph13120469<i>N</i>-(Hydroxyalkyl) Derivatives of <i>tris</i>(1<i>H</i>-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological EvaluationSergey N. Lavrenov0Elena B. Isakova1Alexey A. Panov2Alexander Y. Simonov3Viktor V. Tatarskiy4Alexey S. Trenin5Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, RussiaGause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, RussiaGause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, RussiaGause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, RussiaN. N. Blokhin Russian Cancer Research Center, 24 Kashirskoe Shosse, 115478 Moscow, RussiaGause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, RussiaThe 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 <i>tris</i>(1<i>H</i>-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 <i>Staphylococcus epidermidis</i> (1.0 and 0.5 μg/mL, respectively) and moderate activity against Gram-negative bacteria <i>Escherichia coli</i> (8 μg/mL) and <i>Klebsiella pneumonia</i> (2 and 8 μg/mL, respectively). However, they have no activity against <i>Salmonella cholerasuis</i> and <i>Pseudomonas aeruginosa</i>. 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.https://www.mdpi.com/1424-8247/13/12/469<i>tris</i>(1<i>H</i>-indol-3-yl)methyliumturbomycinindole derivativesantibacterial actionovercoming of drug resistance |
| spellingShingle | Sergey N. Lavrenov Elena B. Isakova Alexey A. Panov Alexander Y. Simonov Viktor V. Tatarskiy Alexey S. Trenin <i>N</i>-(Hydroxyalkyl) Derivatives of <i>tris</i>(1<i>H</i>-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation Pharmaceuticals <i>tris</i>(1<i>H</i>-indol-3-yl)methylium turbomycin indole derivatives antibacterial action overcoming of drug resistance |
| title | <i>N</i>-(Hydroxyalkyl) Derivatives of <i>tris</i>(1<i>H</i>-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation |
| title_full | <i>N</i>-(Hydroxyalkyl) Derivatives of <i>tris</i>(1<i>H</i>-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation |
| title_fullStr | <i>N</i>-(Hydroxyalkyl) Derivatives of <i>tris</i>(1<i>H</i>-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation |
| title_full_unstemmed | <i>N</i>-(Hydroxyalkyl) Derivatives of <i>tris</i>(1<i>H</i>-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation |
| title_short | <i>N</i>-(Hydroxyalkyl) Derivatives of <i>tris</i>(1<i>H</i>-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation |
| title_sort | i n i hydroxyalkyl derivatives of i tris i 1 i h i indol 3 yl methylium salts as promising antibacterial agents synthesis and biological evaluation |
| topic | <i>tris</i>(1<i>H</i>-indol-3-yl)methylium turbomycin indole derivatives antibacterial action overcoming of drug resistance |
| url | https://www.mdpi.com/1424-8247/13/12/469 |
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