Ester derivatives of Dictyostelium differentiation-inducing factors exhibit antibacterial activity, possibly via a prodrug-like function
Abstract Objective Dictyostelium differentiation-inducing factors 1 and 3 [DIF-1 (1) and DIF-3 (2), respectively], along with their derivatives, such as Ph-DIF-1 (3) and Bu-DIF-3 (4), demonstrate antibacterial activity in vitro against Gram-positive bacteria, including methicillin-sensitive Staphylo...
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BMC
2025-01-01
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| Series: | BMC Research Notes |
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| Online Access: | https://doi.org/10.1186/s13104-025-07122-5 |
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| author | Katsunori Takahashi Haruhisa Kikuchi Takehiro Nishimura Hirotaka Ishigaki Yusuke Miura Ayuko Takahashi Yuzuru Kubohara |
| author_facet | Katsunori Takahashi Haruhisa Kikuchi Takehiro Nishimura Hirotaka Ishigaki Yusuke Miura Ayuko Takahashi Yuzuru Kubohara |
| author_sort | Katsunori Takahashi |
| collection | DOAJ |
| description | Abstract Objective Dictyostelium differentiation-inducing factors 1 and 3 [DIF-1 (1) and DIF-3 (2), respectively], along with their derivatives, such as Ph-DIF-1 (3) and Bu-DIF-3 (4), demonstrate antibacterial activity in vitro against Gram-positive bacteria, including methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-sensitive Enterococcus faecalis (VSE), and vancomycin-resistant Enterococcus faecium [VRE (VanA)]. This study investigates the therapeutic potential of DIF compounds against these Gram-positive bacteria. Results In vitro tests revealed that the antibacterial activity of 3 and 4 was lost in the presence of human serum albumin (HSA), suggesting that HSA might inhibit their effectiveness. Further evaluation of less hydrophobic derivatives, DIF-1-NH2 (5) and NH2-Bu-DIF-3 (6), showed no antibacterial activity, even in the absence of HSA. However, ester derivatives Ph-DIF-1(AHA) (7) and Bu-DIF-3(2Ac) (8) exhibited antibacterial activity against the target bacteria in vitro, although this activity was also lost in the presence of HSA. We hypothesize that these ester derivatives may function as prodrugs, with their antibacterial activity possibly restored by hydrolysis through bacterial esterases. The results suggest that suitable ester modifications could enhance the in vivo antibacterial potential of DIF compounds, particularly if they can bypass HSA binding and be activated by bacterial enzymes. |
| format | Article |
| id | doaj-art-76d318e555664fb18888793a7613c0b0 |
| institution | Kabale University |
| issn | 1756-0500 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Research Notes |
| spelling | doaj-art-76d318e555664fb18888793a7613c0b02025-02-02T12:07:00ZengBMCBMC Research Notes1756-05002025-01-011811910.1186/s13104-025-07122-5Ester derivatives of Dictyostelium differentiation-inducing factors exhibit antibacterial activity, possibly via a prodrug-like functionKatsunori Takahashi0Haruhisa Kikuchi1Takehiro Nishimura2Hirotaka Ishigaki3Yusuke Miura4Ayuko Takahashi5Yuzuru Kubohara6Department of Medical Technology, Faculty of Health Science, Gunma Paz UniversityDivision of Natural Medicines, Faculty of Pharmacy, Keio UniversityDivision of Natural Medicines, Faculty of Pharmacy, Keio UniversityDepartment of Medical Technology, Faculty of Health Science, Gunma Paz UniversityDepartment of Medical Technology, Faculty of Health Science, Gunma Paz UniversityDepartment of Medical Technology, Faculty of Health Science, Gunma Paz UniversityLaboratory of Health and Life Science, Graduate School of Health and Sports Science, Juntendo UniversityAbstract Objective Dictyostelium differentiation-inducing factors 1 and 3 [DIF-1 (1) and DIF-3 (2), respectively], along with their derivatives, such as Ph-DIF-1 (3) and Bu-DIF-3 (4), demonstrate antibacterial activity in vitro against Gram-positive bacteria, including methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-sensitive Enterococcus faecalis (VSE), and vancomycin-resistant Enterococcus faecium [VRE (VanA)]. This study investigates the therapeutic potential of DIF compounds against these Gram-positive bacteria. Results In vitro tests revealed that the antibacterial activity of 3 and 4 was lost in the presence of human serum albumin (HSA), suggesting that HSA might inhibit their effectiveness. Further evaluation of less hydrophobic derivatives, DIF-1-NH2 (5) and NH2-Bu-DIF-3 (6), showed no antibacterial activity, even in the absence of HSA. However, ester derivatives Ph-DIF-1(AHA) (7) and Bu-DIF-3(2Ac) (8) exhibited antibacterial activity against the target bacteria in vitro, although this activity was also lost in the presence of HSA. We hypothesize that these ester derivatives may function as prodrugs, with their antibacterial activity possibly restored by hydrolysis through bacterial esterases. The results suggest that suitable ester modifications could enhance the in vivo antibacterial potential of DIF compounds, particularly if they can bypass HSA binding and be activated by bacterial enzymes.https://doi.org/10.1186/s13104-025-07122-5Dictyostelium discoideumAntibacterial agentMethicillin-resistant Staphylococcus aureusVancomycin-resistant Enterococcus faecium |
| spellingShingle | Katsunori Takahashi Haruhisa Kikuchi Takehiro Nishimura Hirotaka Ishigaki Yusuke Miura Ayuko Takahashi Yuzuru Kubohara Ester derivatives of Dictyostelium differentiation-inducing factors exhibit antibacterial activity, possibly via a prodrug-like function BMC Research Notes Dictyostelium discoideum Antibacterial agent Methicillin-resistant Staphylococcus aureus Vancomycin-resistant Enterococcus faecium |
| title | Ester derivatives of Dictyostelium differentiation-inducing factors exhibit antibacterial activity, possibly via a prodrug-like function |
| title_full | Ester derivatives of Dictyostelium differentiation-inducing factors exhibit antibacterial activity, possibly via a prodrug-like function |
| title_fullStr | Ester derivatives of Dictyostelium differentiation-inducing factors exhibit antibacterial activity, possibly via a prodrug-like function |
| title_full_unstemmed | Ester derivatives of Dictyostelium differentiation-inducing factors exhibit antibacterial activity, possibly via a prodrug-like function |
| title_short | Ester derivatives of Dictyostelium differentiation-inducing factors exhibit antibacterial activity, possibly via a prodrug-like function |
| title_sort | ester derivatives of dictyostelium differentiation inducing factors exhibit antibacterial activity possibly via a prodrug like function |
| topic | Dictyostelium discoideum Antibacterial agent Methicillin-resistant Staphylococcus aureus Vancomycin-resistant Enterococcus faecium |
| url | https://doi.org/10.1186/s13104-025-07122-5 |
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