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Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents

We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were...

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Autores principales: Antoci, Vasilichia, Oniciuc, Liliana, Amariucai-Mantu, Dorina, Moldoveanu, Costel, Mangalagiu, Violeta, Amarandei, Andreea Madalina, Lungu, Claudiu N., Dunca, Simona, Mangalagiu, Ionel I., Zbancioc, Gheorghita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067460/
https://www.ncbi.nlm.nih.gov/pubmed/33917439
http://dx.doi.org/10.3390/ph14040335
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author Antoci, Vasilichia
Oniciuc, Liliana
Amariucai-Mantu, Dorina
Moldoveanu, Costel
Mangalagiu, Violeta
Amarandei, Andreea Madalina
Lungu, Claudiu N.
Dunca, Simona
Mangalagiu, Ionel I.
Zbancioc, Gheorghita
author_facet Antoci, Vasilichia
Oniciuc, Liliana
Amariucai-Mantu, Dorina
Moldoveanu, Costel
Mangalagiu, Violeta
Amarandei, Andreea Madalina
Lungu, Claudiu N.
Dunca, Simona
Mangalagiu, Ionel I.
Zbancioc, Gheorghita
author_sort Antoci, Vasilichia
collection PubMed
description We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, (1)H-NMR, (13)C-NMR). The antimicrobial assay reveals that the BQS salts have an excellent quasi-nonselective antifungal activity against the fungus Candida albicans (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium Staphylococcus aureus. The PBQC compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzo[f]quinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the BQS salts. Studies of the interaction of each BQS salt 3a–o with ATP synthase in the formed complex, reveal that salts 3j, 3i, and 3n have the best fit in a complex with ATP synthase. Study of the interaction of each BQS salt 3a-o with TOPO II in the formed complex reveals that salts 3j and 3n have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the BQS salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds 3e and 3f (from the aliphatic series), respectively, and 3i, 3j and 3n (from the aromatic series), are promising leading drug candidates.
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spelling pubmed-80674602021-04-25 Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents Antoci, Vasilichia Oniciuc, Liliana Amariucai-Mantu, Dorina Moldoveanu, Costel Mangalagiu, Violeta Amarandei, Andreea Madalina Lungu, Claudiu N. Dunca, Simona Mangalagiu, Ionel I. Zbancioc, Gheorghita Pharmaceuticals (Basel) Article We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, (1)H-NMR, (13)C-NMR). The antimicrobial assay reveals that the BQS salts have an excellent quasi-nonselective antifungal activity against the fungus Candida albicans (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium Staphylococcus aureus. The PBQC compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzo[f]quinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the BQS salts. Studies of the interaction of each BQS salt 3a–o with ATP synthase in the formed complex, reveal that salts 3j, 3i, and 3n have the best fit in a complex with ATP synthase. Study of the interaction of each BQS salt 3a-o with TOPO II in the formed complex reveals that salts 3j and 3n have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the BQS salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds 3e and 3f (from the aliphatic series), respectively, and 3i, 3j and 3n (from the aromatic series), are promising leading drug candidates. MDPI 2021-04-06 /pmc/articles/PMC8067460/ /pubmed/33917439 http://dx.doi.org/10.3390/ph14040335 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Antoci, Vasilichia
Oniciuc, Liliana
Amariucai-Mantu, Dorina
Moldoveanu, Costel
Mangalagiu, Violeta
Amarandei, Andreea Madalina
Lungu, Claudiu N.
Dunca, Simona
Mangalagiu, Ionel I.
Zbancioc, Gheorghita
Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents
title Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents
title_full Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents
title_fullStr Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents
title_full_unstemmed Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents
title_short Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents
title_sort benzoquinoline derivatives: a straightforward and efficient route to antibacterial and antifungal agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067460/
https://www.ncbi.nlm.nih.gov/pubmed/33917439
http://dx.doi.org/10.3390/ph14040335
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