Pub Date : 2025-07-16DOI: 10.1038/s41429-025-00848-1
Ari Soares de Oliveira Neto, Maria Eliza Samuel Amorim, Rodrigo Luiz Fabri, Rene Oliveira do Couto, Marcelo Gonzaga de Freitas Araújo
The assignment of new therapeutic purposes to drugs, known as drug repositioning, has been an important ally in the search for new antifungal drugs. Statin compounds, which are used systemically as cholesterol-lowering, may also exert direct antifungal effects, since the statins are drugs that act to prevent sterol synthesis in both humans and fungi and for this reason they are drug promising to combat mycoses. We evaluate the in vivo efficacy of an atorvastatin-loaded topic emulgel (0.75%, 1.5%, or 3.0% m/m) in an in vivo experimental model Tinea pedis. The results showed that the cutaneous delivery-atorvastatin showed total score reduction after seven days of treatment. We concluded that atorvastatin may be a promising drug for the treatment of superficial and cutaneous mycosis.
{"title":"In vivo efficacy of atorvastatin in the treatment of Tinea pedis: stepping forward into drug repositioning","authors":"Ari Soares de Oliveira Neto, Maria Eliza Samuel Amorim, Rodrigo Luiz Fabri, Rene Oliveira do Couto, Marcelo Gonzaga de Freitas Araújo","doi":"10.1038/s41429-025-00848-1","DOIUrl":"10.1038/s41429-025-00848-1","url":null,"abstract":"The assignment of new therapeutic purposes to drugs, known as drug repositioning, has been an important ally in the search for new antifungal drugs. Statin compounds, which are used systemically as cholesterol-lowering, may also exert direct antifungal effects, since the statins are drugs that act to prevent sterol synthesis in both humans and fungi and for this reason they are drug promising to combat mycoses. We evaluate the in vivo efficacy of an atorvastatin-loaded topic emulgel (0.75%, 1.5%, or 3.0% m/m) in an in vivo experimental model Tinea pedis. The results showed that the cutaneous delivery-atorvastatin showed total score reduction after seven days of treatment. We concluded that atorvastatin may be a promising drug for the treatment of superficial and cutaneous mycosis.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 10","pages":"600-605"},"PeriodicalIF":2.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-14DOI: 10.1038/s41429-025-00850-7
Dong H. Kwon, Mital Vasoya, Danya Sankaranarayanan
Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and Pseudomonas aeruginosa, associated with systemic and hospital-acquired infections, have spread globally and pose a significant public health concern. Glutathione is a multifunctional thiol-antioxidant compound synthesized in most Gram-negative bacteria and crucial in maintaining intracellular redox homeostasis. Exogenous glutathione exhibits antibiotic properties and has differential effects on conventional antibiotics. Therefore, its effect on specific antibiotics needs to be clarified in bacterial species. In this study, we investigated the antibacterial activity of glutathione and its effect on meropenem susceptibility in KPC-producing bacteria. Two major KPC-encoding genes cloned from two different clinical KPC-producing K. pneumoniae were introduced into E. coli and P. aeruginosa. Then, the KPC-producing K. pneumoniae, E. coli, and P. aeruginosa were used for minimum inhibitory concentration (MIC), population analysis, checkerboard, and time-killing assays. The results showed that glutathione exhibited antibacterial activity at >10 mM in K. pneumoniae, E. coli, and P. aeruginosa. MIC levels of meropenem combined with 10 mM of glutathione were synergistically decreased by 8- to ≥ 256-fold in KPC-producing bacteria. Furthermore, this combination killed 100% of the KPC-producing bacteria at 2 to 4 μg mL−1 of meropenem. These findings suggest that exogenous glutathione may be applicable in fighting infections caused by KPC-producing bacteria.
{"title":"The effect of exogenous glutathione on meropenem susceptibility in Klebsiella pneumoniae-carbapenemases (KPC)-producing bacteria","authors":"Dong H. Kwon, Mital Vasoya, Danya Sankaranarayanan","doi":"10.1038/s41429-025-00850-7","DOIUrl":"10.1038/s41429-025-00850-7","url":null,"abstract":"Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and Pseudomonas aeruginosa, associated with systemic and hospital-acquired infections, have spread globally and pose a significant public health concern. Glutathione is a multifunctional thiol-antioxidant compound synthesized in most Gram-negative bacteria and crucial in maintaining intracellular redox homeostasis. Exogenous glutathione exhibits antibiotic properties and has differential effects on conventional antibiotics. Therefore, its effect on specific antibiotics needs to be clarified in bacterial species. In this study, we investigated the antibacterial activity of glutathione and its effect on meropenem susceptibility in KPC-producing bacteria. Two major KPC-encoding genes cloned from two different clinical KPC-producing K. pneumoniae were introduced into E. coli and P. aeruginosa. Then, the KPC-producing K. pneumoniae, E. coli, and P. aeruginosa were used for minimum inhibitory concentration (MIC), population analysis, checkerboard, and time-killing assays. The results showed that glutathione exhibited antibacterial activity at >10 mM in K. pneumoniae, E. coli, and P. aeruginosa. MIC levels of meropenem combined with 10 mM of glutathione were synergistically decreased by 8- to ≥ 256-fold in KPC-producing bacteria. Furthermore, this combination killed 100% of the KPC-producing bacteria at 2 to 4 μg mL−1 of meropenem. These findings suggest that exogenous glutathione may be applicable in fighting infections caused by KPC-producing bacteria.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 10","pages":"633-637"},"PeriodicalIF":2.7,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-10DOI: 10.1038/s41429-025-00842-7
Md. Mehebub Al Raji, Desy Wulan Triningsih, Agus Trianto, Yasuhiro Igarashi
Halobacin (1), a new glycosylated acyloin derivative, was isolated from the fermentation broth of a coral-associated bacterium Halobacillus sp. DUNA-S15. The structure of 1 was determined based on NMR and MS analyses and the absolute configuration of the sugar moiety was determined by diastereomeric HPLC separation using chiral derivatization. Compound 1 was inactive in antimicrobial and cytotoxicity assays but suppressed the root growth of germinated seeds of lettuce and barnyard millet to ca 30% at 1 µg ml−1 and ca 70% at 10 µg ml−1 compared to the nontreated seeds.
{"title":"Halobacin, a herbicidal acyloin derivative from a marine bacterium of the genus Halobacillus","authors":"Md. Mehebub Al Raji, Desy Wulan Triningsih, Agus Trianto, Yasuhiro Igarashi","doi":"10.1038/s41429-025-00842-7","DOIUrl":"10.1038/s41429-025-00842-7","url":null,"abstract":"Halobacin (1), a new glycosylated acyloin derivative, was isolated from the fermentation broth of a coral-associated bacterium Halobacillus sp. DUNA-S15. The structure of 1 was determined based on NMR and MS analyses and the absolute configuration of the sugar moiety was determined by diastereomeric HPLC separation using chiral derivatization. Compound 1 was inactive in antimicrobial and cytotoxicity assays but suppressed the root growth of germinated seeds of lettuce and barnyard millet to ca 30% at 1 µg ml−1 and ca 70% at 10 µg ml−1 compared to the nontreated seeds.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 9","pages":"569-572"},"PeriodicalIF":2.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stressors like translational inhibitors stall protein synthesis and produce a response specific to temperature extremes. Yet, little is known about the expression of temperature-related proteins, particularly the cold shock proteins (Csps), under antibiotic stress. Here, we demonstrate the expression pattern of all nine Csps of Escherichia coli to a sub-lethal concentration of chloramphenicol, tetracycline, gentamicin, kanamycin, and ampicillin. The five antibiotics represent different classes that target different areas of the translational apparatus and the cell wall. To investigate whether all nine csps are expressed in response to antibiotics, we measured the survival of E. coli across the antibiotics and further analyzed expression by qPCR. We find that the expression pattern of csps varies between the Csp groups, and within a Csp group, certain members are more prominently expressed than the rest. The C-group antibiotics, which include chloramphenicol and tetracycline, upregulated the expression of cold-inducible and uncharacterized Csp groups. The H-group antibiotic, kanamycin, along with the uncharacterized antibiotics gentamicin and ampicillin, induced csps as well as heat shock proteins (hsps). To the best of our knowledge, this study is the first to demonstrate the expression pattern of all nine csps in response to antibiotics. Moreover, our study has implications for understanding the triggers of Csps and, in a broader context, their role in stress tolerance, virulence, and pathogenesis.
{"title":"Altered gene expression of cold shock proteins under antibiotic exposure","authors":"Evieann Cardoza, Darsh Vira, Advait Rao, Harinder Singh","doi":"10.1038/s41429-025-00849-0","DOIUrl":"10.1038/s41429-025-00849-0","url":null,"abstract":"Stressors like translational inhibitors stall protein synthesis and produce a response specific to temperature extremes. Yet, little is known about the expression of temperature-related proteins, particularly the cold shock proteins (Csps), under antibiotic stress. Here, we demonstrate the expression pattern of all nine Csps of Escherichia coli to a sub-lethal concentration of chloramphenicol, tetracycline, gentamicin, kanamycin, and ampicillin. The five antibiotics represent different classes that target different areas of the translational apparatus and the cell wall. To investigate whether all nine csps are expressed in response to antibiotics, we measured the survival of E. coli across the antibiotics and further analyzed expression by qPCR. We find that the expression pattern of csps varies between the Csp groups, and within a Csp group, certain members are more prominently expressed than the rest. The C-group antibiotics, which include chloramphenicol and tetracycline, upregulated the expression of cold-inducible and uncharacterized Csp groups. The H-group antibiotic, kanamycin, along with the uncharacterized antibiotics gentamicin and ampicillin, induced csps as well as heat shock proteins (hsps). To the best of our knowledge, this study is the first to demonstrate the expression pattern of all nine csps in response to antibiotics. Moreover, our study has implications for understanding the triggers of Csps and, in a broader context, their role in stress tolerance, virulence, and pathogenesis.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 10","pages":"621-632"},"PeriodicalIF":2.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bacterial interactions can affect the production of secondary metabolites and, therefore, provide a promising approach to exploring new microbial compounds. In this study, we screened actinomycetes isolated from Hegura Island, Ishikawa Prefecture, Japan, to discover new antibiotics through combined-culture with Tsukamurella pulmonis TP-B0596. Three new phenazine-class antibiotics, griseoluteins T (1), C (2), and D (3), along with two known related metabolites, griseoluteic acid (4) and griseolutein A (5), were detected in both mono- and combined-cultures of Streptomyces seoulensis HEK131 with T. pulmonis at different production levels. Detailed spectroscopic analysis revealed that 1 contained a dihydrophenazine core, and was converted to 5 by accepting oxidation spontaneously. 1, containing a dihydrophenazine group, was relatively unstable under oxidative conditions, and the addition of ascorbate was required during the isolation of the compound. 2 and 3 were found to be cysteine-adducts analogous to 4, and their productivity was increased in the combined-culture. We further assessed the antibacterial activities of 1 against clinically significant Gram-positive pathogenic bacteria, including 30 methicillin-resistant Staphylococcus aureus (MRSA), 27 vancomycin-resistant Enterococci (VRE), and 17 Clostridioides difficile. Notably, 1 was found to possess higher antibacterial activity against these microorganisms than several clinically important antibiotics, while displaying lower cytotoxicity against HeLa-S3 cells.
{"title":"Griseolutein T from Streptomyces seoulensis, newly identified via combined-culture with Tsukamurella pulmonis, as an efficacious therapeutic agent against multidrug-resistant bacteria","authors":"Sung-Jin Kawai, Shumpei Asamizu, Hiroaki Suzuki, Hiroyasu Onaka, Yoshichika Arakawa, Kouji Kimura, Makoto Ojika","doi":"10.1038/s41429-025-00846-3","DOIUrl":"10.1038/s41429-025-00846-3","url":null,"abstract":"Bacterial interactions can affect the production of secondary metabolites and, therefore, provide a promising approach to exploring new microbial compounds. In this study, we screened actinomycetes isolated from Hegura Island, Ishikawa Prefecture, Japan, to discover new antibiotics through combined-culture with Tsukamurella pulmonis TP-B0596. Three new phenazine-class antibiotics, griseoluteins T (1), C (2), and D (3), along with two known related metabolites, griseoluteic acid (4) and griseolutein A (5), were detected in both mono- and combined-cultures of Streptomyces seoulensis HEK131 with T. pulmonis at different production levels. Detailed spectroscopic analysis revealed that 1 contained a dihydrophenazine core, and was converted to 5 by accepting oxidation spontaneously. 1, containing a dihydrophenazine group, was relatively unstable under oxidative conditions, and the addition of ascorbate was required during the isolation of the compound. 2 and 3 were found to be cysteine-adducts analogous to 4, and their productivity was increased in the combined-culture. We further assessed the antibacterial activities of 1 against clinically significant Gram-positive pathogenic bacteria, including 30 methicillin-resistant Staphylococcus aureus (MRSA), 27 vancomycin-resistant Enterococci (VRE), and 17 Clostridioides difficile. Notably, 1 was found to possess higher antibacterial activity against these microorganisms than several clinically important antibiotics, while displaying lower cytotoxicity against HeLa-S3 cells.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 9","pages":"542-551"},"PeriodicalIF":2.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Streptomyces strain TP-A0890T, isolated from a soil sample, is a producer of FR-900452 and A-74863a. The taxonomic status was clarified by a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain was closely related to Streptomyces coriariae, with similarity of 99.7%. Strain TP-A0890T comprised ll-diaminopimelic acid, glutamic acid, glycine and alanine in its peptidoglycan. The predominant menaquinones were MK-9(H8) and MK-9(H6), and major fatty acids were anteiso-C17:0, anteiso-C15:0, iso-C16:0 and iso-C17:0. The chemotaxonomic features matched those described for the genus Streptomyces. The genome size and G + C content were 8.72 Mb and 71.5%, respectively. The results of digital DNA-DNA hybridization along with differences in phenotypic characteristics between the strains suggested strain TP-A0890T to assign to a novel species, for which Streptomyces maremycinicus sp. nov. is proposed; the type strain is TP-A0890T ( = NBRC 110468T). We also show that Streptomyces strain B9173, a producer of FR-900452 and maremycins that was isolated from coastal sediment in Chile, belonged to S. maremycinicus. Twenty-two to 23 secondary metabolite-biosynthetic gene clusters (smBGCs) were present in the genomes of S. maremycinicus strains. Seventeen of them were conserved in the genome of S. coriariae CMB-FBT but the others were not.
{"title":"Streptomyces maremycinicus sp. nov. and its secondary metabolite-biosynthetic gene clusters","authors":"Hisayuki Komaki, Yasuhiro Igarashi, Tomohiko Tamura","doi":"10.1038/s41429-025-00844-5","DOIUrl":"10.1038/s41429-025-00844-5","url":null,"abstract":"Streptomyces strain TP-A0890T, isolated from a soil sample, is a producer of FR-900452 and A-74863a. The taxonomic status was clarified by a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain was closely related to Streptomyces coriariae, with similarity of 99.7%. Strain TP-A0890T comprised ll-diaminopimelic acid, glutamic acid, glycine and alanine in its peptidoglycan. The predominant menaquinones were MK-9(H8) and MK-9(H6), and major fatty acids were anteiso-C17:0, anteiso-C15:0, iso-C16:0 and iso-C17:0. The chemotaxonomic features matched those described for the genus Streptomyces. The genome size and G + C content were 8.72 Mb and 71.5%, respectively. The results of digital DNA-DNA hybridization along with differences in phenotypic characteristics between the strains suggested strain TP-A0890T to assign to a novel species, for which Streptomyces maremycinicus sp. nov. is proposed; the type strain is TP-A0890T ( = NBRC 110468T). We also show that Streptomyces strain B9173, a producer of FR-900452 and maremycins that was isolated from coastal sediment in Chile, belonged to S. maremycinicus. Twenty-two to 23 secondary metabolite-biosynthetic gene clusters (smBGCs) were present in the genomes of S. maremycinicus strains. Seventeen of them were conserved in the genome of S. coriariae CMB-FBT but the others were not.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 9","pages":"560-568"},"PeriodicalIF":2.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1038/s41429-025-00839-2
Alicia M. Gutiérrez-Mauricio, Juan Valentín Trujillo-Paez, Luis Alberto Trejo-Martinez, Bruno Rivas-Santiago, Paola Pérez-García, Saúl Noriega, Juan Ernesto López-Ramos, Jaime Cardoso-Ortiz, Adrián Rodríguez-Carlos
Tuberculosis (TB) is a contagious infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). It is transmitted through small particles in the air (<5 µm) expelled by active tuberculosis patients; when inhaled by a new host, they can potentially cause infection. Nowadays, TB is still the major cause of morbidity and mortality by a single infectious agent, this is further exacerbated by the worldwide emergence of multidrug-resistant strains of Mtb. Thus, effective methods of diagnosis, prophylaxis, and new pharmacological therapies must be carried out in order to control this disease. Fluoroquinolones (FQ) are synthetic antibiotics with a broad spectrum against Gram-negative and Gram-positive bacteria, including M. tuberculosis. The treatment with FQ plays an important role in managing drug-resistant tuberculosis. Modifications on FQ structure have been extensively studied, thereby, four generations of FQ have emerged having a broad spectrum of antibacterial properties. These modifications improve the overall efficiency of FQ by increasing tissue penetration, reducing side effects, and addressing emerging bacterial resistance. In this scenario, current trends on FQ research have focused on new synthetic approaches that allow fluoroquinolones to address the worldwide issue of multidrug-resistant tuberculosis. The aim of this review is to highlight the overall effects of newly synthesized FQ molecules having antitubercular activity.
结核病（TB）是由结核分枝杆菌（Mtb）引起的传染性疾病。它通过空气中的小颗粒传播(
{"title":"Tuberculosis drug development; fluoroquinolone structural tailoring","authors":"Alicia M. Gutiérrez-Mauricio, Juan Valentín Trujillo-Paez, Luis Alberto Trejo-Martinez, Bruno Rivas-Santiago, Paola Pérez-García, Saúl Noriega, Juan Ernesto López-Ramos, Jaime Cardoso-Ortiz, Adrián Rodríguez-Carlos","doi":"10.1038/s41429-025-00839-2","DOIUrl":"10.1038/s41429-025-00839-2","url":null,"abstract":"Tuberculosis (TB) is a contagious infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). It is transmitted through small particles in the air (<5 µm) expelled by active tuberculosis patients; when inhaled by a new host, they can potentially cause infection. Nowadays, TB is still the major cause of morbidity and mortality by a single infectious agent, this is further exacerbated by the worldwide emergence of multidrug-resistant strains of Mtb. Thus, effective methods of diagnosis, prophylaxis, and new pharmacological therapies must be carried out in order to control this disease. Fluoroquinolones (FQ) are synthetic antibiotics with a broad spectrum against Gram-negative and Gram-positive bacteria, including M. tuberculosis. The treatment with FQ plays an important role in managing drug-resistant tuberculosis. Modifications on FQ structure have been extensively studied, thereby, four generations of FQ have emerged having a broad spectrum of antibacterial properties. These modifications improve the overall efficiency of FQ by increasing tissue penetration, reducing side effects, and addressing emerging bacterial resistance. In this scenario, current trends on FQ research have focused on new synthetic approaches that allow fluoroquinolones to address the worldwide issue of multidrug-resistant tuberculosis. The aim of this review is to highlight the overall effects of newly synthesized FQ molecules having antitubercular activity.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 9","pages":"517-534"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41429-025-00839-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Streptospherin A (1), which has pentasubstituted benzene and tetrahydropyran moieties, was recently isolated in our laboratory from Streptomyces sp. KUSC-240 as a novel inhibitor of cancer stem cell (CSC) sphere formation. Given the potential of CSCs as target for cancer therapy because of their high malignancy, identification of CSC inhibitors is urgently needed. The chemical structure and biological activity of 1 prompted us to isolate other derivatives from Streptomyces sp. KUSC-240, leading here to the identification of new streptospherins B–F (2–6). Their planar structures were determined by HR-ESI-MS and NMR analyses. The absolute configuration of 4 was proposed by using a modified Mosher’s method, acetonide formation, and the J-based configuration analysis (JBCA) method. The absolute configurations of 3 and 5 were also determined by using ECD spectra and comparison with that of 4. Analysis of the whole genome sequence of the producing strain suggested a plausible biosynthesis pathway for 3–5. Compounds 2–6 inhibited CSC sphere formation and suppressed CSC growth, indicating that streptospherins are promising seed compounds for CSC inhibitors for cancer chemotherapy.
{"title":"Isolation and structure determination of streptospherins B–F, novel cancer stem cell inhibitors, produced by Streptomyces sp. KUSC-240","authors":"Morihiro Shibasaki, Hiroaki Ikeda, Ami Mimura, Junko Hashimoto, Taiki Suo, Takefumi Kuranaga, Kazuo Shin-ya, Masaya Imoto, Hideaki Kakeya","doi":"10.1038/s41429-025-00843-6","DOIUrl":"10.1038/s41429-025-00843-6","url":null,"abstract":"Streptospherin A (1), which has pentasubstituted benzene and tetrahydropyran moieties, was recently isolated in our laboratory from Streptomyces sp. KUSC-240 as a novel inhibitor of cancer stem cell (CSC) sphere formation. Given the potential of CSCs as target for cancer therapy because of their high malignancy, identification of CSC inhibitors is urgently needed. The chemical structure and biological activity of 1 prompted us to isolate other derivatives from Streptomyces sp. KUSC-240, leading here to the identification of new streptospherins B–F (2–6). Their planar structures were determined by HR-ESI-MS and NMR analyses. The absolute configuration of 4 was proposed by using a modified Mosher’s method, acetonide formation, and the J-based configuration analysis (JBCA) method. The absolute configurations of 3 and 5 were also determined by using ECD spectra and comparison with that of 4. Analysis of the whole genome sequence of the producing strain suggested a plausible biosynthesis pathway for 3–5. Compounds 2–6 inhibited CSC sphere formation and suppressed CSC growth, indicating that streptospherins are promising seed compounds for CSC inhibitors for cancer chemotherapy.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 9","pages":"535-541"},"PeriodicalIF":2.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41429-025-00843-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fluostatins are a class of compounds having four unique ring systems. They were originally isolated as dipeptidyl peptidase III (DPP3) inhibitors, and various derivatives and activities have been reported. In this study, fluostatin A, which is difficult to prepare by fermentative production, was effectively prepared by the transformation of fluostatin B. A new derivative, fluostatin Y, and a new naturally occurring derivative, fluostatin B2, were obtained, and their structures were determined. Furthermore, the bioactivity, DPP3 inhibitory activity, and antibacterial and cytotoxic activities were examined.
{"title":"Study about fluostatins: efficient preparation of fluostatin A and discovery of fluostatin derivatives from Streptomyces sp. TA-3391","authors":"Shigehiro Tohyama, Seiji Nukui, Masaki Hatano, Chigusa Hayashi, Isao Momose, Masayuki Igarashi","doi":"10.1038/s41429-025-00841-8","DOIUrl":"10.1038/s41429-025-00841-8","url":null,"abstract":"Fluostatins are a class of compounds having four unique ring systems. They were originally isolated as dipeptidyl peptidase III (DPP3) inhibitors, and various derivatives and activities have been reported. In this study, fluostatin A, which is difficult to prepare by fermentative production, was effectively prepared by the transformation of fluostatin B. A new derivative, fluostatin Y, and a new naturally occurring derivative, fluostatin B2, were obtained, and their structures were determined. Furthermore, the bioactivity, DPP3 inhibitory activity, and antibacterial and cytotoxic activities were examined.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 9","pages":"552-559"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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