Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking
In the present study, we designed and synthesized thiolated <b>VK3</b> analogs (<b>VK3a–g</b>) along with an extensive antimicrobial study. After the evaluation of the antibacterial and antifungal activity against various bacterial and fungal strains, we presented an initial...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/5/586 |
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| author | Hatice Yıldırım Mahmut Yıldız Nilüfer Bayrak Emel Mataracı-Kara Mohamed Osman Radwan Ayse Tarbin Jannuzzi Masami Otsuka Mikako Fujita Amaç Fatih TuYuN |
| author_facet | Hatice Yıldırım Mahmut Yıldız Nilüfer Bayrak Emel Mataracı-Kara Mohamed Osman Radwan Ayse Tarbin Jannuzzi Masami Otsuka Mikako Fujita Amaç Fatih TuYuN |
| author_sort | Hatice Yıldırım |
| collection | DOAJ |
| description | In the present study, we designed and synthesized thiolated <b>VK3</b> analogs (<b>VK3a–g</b>) along with an extensive antimicrobial study. After the evaluation of the antibacterial and antifungal activity against various bacterial and fungal strains, we presented an initial structure–activity relationship study on these <b>VK3</b> analogs. In particular, four thiolated <b>VK3</b> analogs exhibited superior biological potency against some Gram-positive bacterial strains, including <i>Staphylococcus aureus</i> (ATCC<sup>®</sup> 29213) and <i>Enterococcus faecalis</i> (ATCC<sup>®</sup> 29212). Next, all thiolated <b>VK3</b> analogs were evaluated for their potential of cell growth inhibition on the NCI-60 cancer cell lines panel. This screening underlined that the thiolated <b>VK3</b> analogs have no visible cytotoxicity on different cancer cell lines. The selected two thiolated <b>VK3</b> analogs (<b>VK3a</b> and <b>VK3b</b>), having minimal hemolytic activity, which also have the lowest MIC values on <i>S. aureus</i> and <i>E. faecalis</i>, were further evaluated for their inhibition capacities on biofilm formation after evaluating their potential in vitro antimicrobial activity against each of the 20 clinically obtained resistant strains of <i>Staphylococcus aureus</i>. <b>VK3b</b> showed excellent antimicrobial activity against clinically resistant <i>S. aureus</i> isolates. Furthermore, the tested molecules showed nearly two log<sub>10</sub> reduction in the viable cell count at six hours according to the time kill curve studies. Although these molecules decreased biofilm attachment about 50%, when sub-MIC concentrations were used these molecules increased the percentage of biofilm formation. The molecular docking of <b>VK3a</b> and <b>VK3b</b> in <i>S. aureus</i> thymidylate kinase was conducted in order to predict their molecular interactions. <b>VK3a</b> and <b>VK3b</b> exhibited excellent lead-likeness properties and pharmacokinetic profiles that qualify them for further optimization and development. In conclusion, since investigating efficient novel antimicrobial molecules is quite difficult, these studies are of high importance, especially in the present era of antimicrobial resistance. |
| first_indexed | 2024-03-10T03:10:01Z |
| format | Article |
| id | doaj.art-f0ee5dd5c886417e906972626573682d |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T03:10:01Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-f0ee5dd5c886417e906972626573682d2023-11-23T12:34:57ZengMDPI AGPharmaceuticals1424-82472022-05-0115558610.3390/ph15050586Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular DockingHatice Yıldırım0Mahmut Yıldız1Nilüfer Bayrak2Emel Mataracı-Kara3Mohamed Osman Radwan4Ayse Tarbin Jannuzzi5Masami Otsuka6Mikako Fujita7Amaç Fatih TuYuN8Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul 34320, TurkeyDepartment of Chemistry, Gebze Technical University, Gebze, Kocaeli 41400, TurkeyDepartment of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul 34320, TurkeyDepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Beyazit, Istanbul 34116, TurkeyMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Beyazit, Istanbul 34116, TurkeyMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Chemistry, Faculty of Science, Istanbul University, Fatih, Istanbul 34126, TurkeyIn the present study, we designed and synthesized thiolated <b>VK3</b> analogs (<b>VK3a–g</b>) along with an extensive antimicrobial study. After the evaluation of the antibacterial and antifungal activity against various bacterial and fungal strains, we presented an initial structure–activity relationship study on these <b>VK3</b> analogs. In particular, four thiolated <b>VK3</b> analogs exhibited superior biological potency against some Gram-positive bacterial strains, including <i>Staphylococcus aureus</i> (ATCC<sup>®</sup> 29213) and <i>Enterococcus faecalis</i> (ATCC<sup>®</sup> 29212). Next, all thiolated <b>VK3</b> analogs were evaluated for their potential of cell growth inhibition on the NCI-60 cancer cell lines panel. This screening underlined that the thiolated <b>VK3</b> analogs have no visible cytotoxicity on different cancer cell lines. The selected two thiolated <b>VK3</b> analogs (<b>VK3a</b> and <b>VK3b</b>), having minimal hemolytic activity, which also have the lowest MIC values on <i>S. aureus</i> and <i>E. faecalis</i>, were further evaluated for their inhibition capacities on biofilm formation after evaluating their potential in vitro antimicrobial activity against each of the 20 clinically obtained resistant strains of <i>Staphylococcus aureus</i>. <b>VK3b</b> showed excellent antimicrobial activity against clinically resistant <i>S. aureus</i> isolates. Furthermore, the tested molecules showed nearly two log<sub>10</sub> reduction in the viable cell count at six hours according to the time kill curve studies. Although these molecules decreased biofilm attachment about 50%, when sub-MIC concentrations were used these molecules increased the percentage of biofilm formation. The molecular docking of <b>VK3a</b> and <b>VK3b</b> in <i>S. aureus</i> thymidylate kinase was conducted in order to predict their molecular interactions. <b>VK3a</b> and <b>VK3b</b> exhibited excellent lead-likeness properties and pharmacokinetic profiles that qualify them for further optimization and development. In conclusion, since investigating efficient novel antimicrobial molecules is quite difficult, these studies are of high importance, especially in the present era of antimicrobial resistance.https://www.mdpi.com/1424-8247/15/5/586antibacterial activityantibiofilm activityVitamin K<i>Staphylococcus aureus</i>thymidylate kinase |
| spellingShingle | Hatice Yıldırım Mahmut Yıldız Nilüfer Bayrak Emel Mataracı-Kara Mohamed Osman Radwan Ayse Tarbin Jannuzzi Masami Otsuka Mikako Fujita Amaç Fatih TuYuN Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking Pharmaceuticals antibacterial activity antibiofilm activity Vitamin K <i>Staphylococcus aureus</i> thymidylate kinase |
| title | Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking |
| title_full | Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking |
| title_fullStr | Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking |
| title_full_unstemmed | Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking |
| title_short | Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking |
| title_sort | promising antibacterial and antifungal agents based on thiolated vitamin k3 analogs synthesis bioevaluation molecular docking |
| topic | antibacterial activity antibiofilm activity Vitamin K <i>Staphylococcus aureus</i> thymidylate kinase |
| url | https://www.mdpi.com/1424-8247/15/5/586 |
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