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Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking

In an attempt to develop effective and potentially active antibacterial and/or antifungal agents, we designed, synthesized, and characterized thiolated CoQ analogs (CoQ1–8) with an extensive antimicrobial study. The antimicrobial profile of these analogs was determined using four Gram-negative bacte...

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Autores principales: Yıldırım, Hatice, Yıldız, Mahmut, Bayrak, Nilüfer, Mataracı-Kara, Emel, Özbek-Çelik, Berna, Otsuka, Masami, Fujita, Mikako, Radwan, Mohamed O., TuYuN, Amaç Fatih
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284347/
https://www.ncbi.nlm.nih.gov/pubmed/35919160
http://dx.doi.org/10.1039/d2ra02136f
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author Yıldırım, Hatice
Yıldız, Mahmut
Bayrak, Nilüfer
Mataracı-Kara, Emel
Özbek-Çelik, Berna
Otsuka, Masami
Fujita, Mikako
Radwan, Mohamed O.
TuYuN, Amaç Fatih
author_facet Yıldırım, Hatice
Yıldız, Mahmut
Bayrak, Nilüfer
Mataracı-Kara, Emel
Özbek-Çelik, Berna
Otsuka, Masami
Fujita, Mikako
Radwan, Mohamed O.
TuYuN, Amaç Fatih
author_sort Yıldırım, Hatice
collection PubMed
description In an attempt to develop effective and potentially active antibacterial and/or antifungal agents, we designed, synthesized, and characterized thiolated CoQ analogs (CoQ1–8) with an extensive antimicrobial study. The antimicrobial profile of these analogs was determined using four Gram-negative bacteria, three Gram-positive bacteria, and three fungi. Because of the fact that the thiolated CoQ analogs were quite effective on all tested Gram-positive bacterial strains, including Staphylococcus aureus (ATCC® 29213) and Enterococcus faecalis (ATCC® 29212), the first two thiolated CoQ analogs emerged as potentially the most desirable ones in this series. Importantly, after the evaluation of the antibacterial and antifungal activity, we presented an initial structure–activity relationship for these CoQ analogs. In addition, the most promising thiolated CoQ analogs (CoQ1 and CoQ2) having the lowest MIC values on all tested Gram-positive bacterial strains, were further evaluated for their inhibition capacities of biofilm formation after evaluating their in vitro potential antimicrobial activity against each of 20 clinically obtained resistant strains of Gram-positive bacteria. CoQ1 and CoQ2 exhibited potential molecular interactions with S. aureus DNA gyrase in addition to excellent pharmacokinetics and lead-likeness profiles. Our findings offer important implications for a potential antimicrobial drug candidate, in particular for the treatment of infections caused by clinically resistant MRSA isolates.
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spelling pubmed-92843472022-08-01 Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking Yıldırım, Hatice Yıldız, Mahmut Bayrak, Nilüfer Mataracı-Kara, Emel Özbek-Çelik, Berna Otsuka, Masami Fujita, Mikako Radwan, Mohamed O. TuYuN, Amaç Fatih RSC Adv Chemistry In an attempt to develop effective and potentially active antibacterial and/or antifungal agents, we designed, synthesized, and characterized thiolated CoQ analogs (CoQ1–8) with an extensive antimicrobial study. The antimicrobial profile of these analogs was determined using four Gram-negative bacteria, three Gram-positive bacteria, and three fungi. Because of the fact that the thiolated CoQ analogs were quite effective on all tested Gram-positive bacterial strains, including Staphylococcus aureus (ATCC® 29213) and Enterococcus faecalis (ATCC® 29212), the first two thiolated CoQ analogs emerged as potentially the most desirable ones in this series. Importantly, after the evaluation of the antibacterial and antifungal activity, we presented an initial structure–activity relationship for these CoQ analogs. In addition, the most promising thiolated CoQ analogs (CoQ1 and CoQ2) having the lowest MIC values on all tested Gram-positive bacterial strains, were further evaluated for their inhibition capacities of biofilm formation after evaluating their in vitro potential antimicrobial activity against each of 20 clinically obtained resistant strains of Gram-positive bacteria. CoQ1 and CoQ2 exhibited potential molecular interactions with S. aureus DNA gyrase in addition to excellent pharmacokinetics and lead-likeness profiles. Our findings offer important implications for a potential antimicrobial drug candidate, in particular for the treatment of infections caused by clinically resistant MRSA isolates. The Royal Society of Chemistry 2022-07-15 /pmc/articles/PMC9284347/ /pubmed/35919160 http://dx.doi.org/10.1039/d2ra02136f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Yıldırım, Hatice
Yıldız, Mahmut
Bayrak, Nilüfer
Mataracı-Kara, Emel
Özbek-Çelik, Berna
Otsuka, Masami
Fujita, Mikako
Radwan, Mohamed O.
TuYuN, Amaç Fatih
Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking
title Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking
title_full Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking
title_fullStr Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking
title_full_unstemmed Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking
title_short Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking
title_sort natural-product-inspired design and synthesis of thiolated coenzyme q analogs as promising agents against gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284347/
https://www.ncbi.nlm.nih.gov/pubmed/35919160
http://dx.doi.org/10.1039/d2ra02136f
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