Journal of Antibiotics最新文献

{"title":"Mechanistic study of the retro-aza-Michael reaction in saccharothriolide L: identification of 2-amino-4-methylphenol as an effective protecting tool for the Michael acceptor","authors":"Shan Lu, Lingling Ren, Di Mao, Hideaki Kakeya","doi":"10.1038/s41429-024-00741-3","DOIUrl":"10.1038/s41429-024-00741-3","url":null,"abstract":"Saccharothriolide L (1), a derivative of saccharothriolides (STLs) produced by the rare actinomycete Saccharotrix sp. A1506, was synthesized through the precursor-directed in situ synthesis (PDSS) method. The structure of 1 was determined by 1D and 2D NMR and HR-ESI-MS data analyses. A comparison of the rate of the retro-aza-Michael reaction between saccharothriolide L (1) and saccharothriolide B (2) indicated that the 2-amino-4-methylphenol group in 1 might be an effective masking tool for highly reactive, bioactive α, β-unsaturated carbonyl compounds.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"544-547"},"PeriodicalIF":2.1,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094591","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}

{"title":"Silkworm model of bacterial infection facilitates the identification of lysocin E, a potent, ultra-rapid bactericidal antibiotic","authors":"Hiroshi Hamamoto","doi":"10.1038/s41429-024-00739-x","DOIUrl":"10.1038/s41429-024-00739-x","url":null,"abstract":"The development of novel antimicrobial agents is required to solve the problem of antimicrobial resistance. We established a quantitative method for evaluating the therapeutic efficacy of antimicrobial agents in a silkworm bacterial infection model. Pharmacokinetic factors are present in the silkworm as well as in mice, and evaluating the therapeutic efficacy of antimicrobial agents is possible in a silkworm infection model, comparable to that in a mammalian model. This silkworm model was used to screen for novel antimicrobial agents with therapeutic efficacy as an indicator. As a result, a new antibiotic, lysocin E, was discovered. Lysocin E has a completely different mechanism of action from existing antimicrobial agents, and its potent bactericidal activity leads to remarkable therapeutic efficacy in a mouse model. In this review, I describe the features of the silkworm model that have contributed to the discovery of lysocin E and its mechanisms of action.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"477-485"},"PeriodicalIF":2.1,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00739-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074543","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}

{"title":"The new seriniquinone glycoside by biological transformation using the deep sea-derived bacterium Bacillus licheniformis KDM612","authors":"Ryota Okamura, Katsuki Kikuchi, Akito Taniguchi, Kenichiro Nagai, Reiko Seki, Satoshi Ohte, Taichi Ohshiro, Masashi Ando, Teruyoshi Tanaka, Takashi Fukuda","doi":"10.1038/s41429-024-00729-z","DOIUrl":"10.1038/s41429-024-00729-z","url":null,"abstract":"Seriniquinone was isolated as a melanoma-selective anti-cancer agent from a culture broth of the marine-derived bacterium Serinicoccus marinus CNJ927 in 2014. It targets the unique small protein, dermcidin, which affects the drug resistance of cancer cells. Due to its significant activity against cancer cells, particularly melanoma, and its unique target, seriniquinone has been developed as a new pharmacophore. However, it has the disadvantage of poor solubility in drug discovery research, which needs to be resolved. A new seriniquinone glycoside (1) was synthesized by the biological transformation of seriniquinone using the deep sea-derived bacterium Bacillus licheniformis KDM612. Compound 1 exhibited selective anti-cancer activity against melanoma, similar to seriniquinone, and was 50-fold more soluble in DMSO than seriniquinone.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"515-521"},"PeriodicalIF":2.1,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075136","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}

{"title":"Antidermatophyte activity and PK/PD of ME1111 in a guinea pig model of tinea corporis","authors":"Naomi Takei-Masuda, Yu Nagira, Natsuki Kubota-Ishida, Tsubasa Chikada, Yuji Tabata, Kazunori Maebashi","doi":"10.1038/s41429-024-00738-y","DOIUrl":"10.1038/s41429-024-00738-y","url":null,"abstract":"Onychomycosis, a superficial fungal infection of the nails, is prevalent in many areas of the world. Topical agents for onychomycosis need to reach the subungual layer and nail bed to exert antifungal activity in the presence of keratin, the major component of the nail. It is difficult to evaluate the efficacy and pharmacodynamics of topical agents for onychomycosis in a non-clinical evaluation system. No consistent animal model has yet been established to predict the efficacy of topical agents for onychomycosis. In this study, we evaluated the pharmacokinetics and pharmacodynamics of ME1111 in a guinea pig model of tinea corporis designed to predict the efficacy of topical medication for onychomycosis in the vicinity of the nail bed. Trichophyton mentagrophytes TIMM1189 was infected on the back skin of guinea pigs, and ME1111 solution (5%, 10%, or 15%) was administered topically, once daily for 14 consecutive days. Following the completion of dosing, segments of skin from the site of infection were excised and cultured. The concentration of ME1111 in the back skin of guinea pigs increased with formulation concentration and correlated with mycological efficacy. We revealed the concentration required for ME1111 to be effective at the site of infection. Further analysis is needed to predict the efficacy of topical agents for onychomycosis by analyzing the relationship between PK/PD around the nail bed and factors such as subungual penetration and permeability.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"533-539"},"PeriodicalIF":2.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071244","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}

{"title":"Correction: New chloptosins B and C from an Embleya strain exhibit synergistic activity against methicillin-resistant Staphylococcus aureus when combined with co-producing compound L-156,602","authors":"Hideki Hashizume, Shigeko Harada, Ryuichi Sawa, Kiyoko Iijima, Yumiko Kubota, Yuko Shibuya, Ryoko Nagasaka, Masaki Hatano, Masayuki Igarashi","doi":"10.1038/s41429-024-00722-6","DOIUrl":"10.1038/s41429-024-00722-6","url":null,"abstract":"","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 7","pages":"475-475"},"PeriodicalIF":2.1,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00722-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960918","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}

{"title":"A new polyene macrolide antibiotic, machidamycin, produced by Streptomyces sp. K22-0017","authors":"Yuta Awano, Ryoya Ishii, Yume Takahashi, Hayama Tsutsumi, Yoshihiro Watanabe, Masaaki Sonoda, Rei Hokari, Masato Iwatsuki, Yuki Inahashi","doi":"10.1038/s41429-024-00737-z","DOIUrl":"10.1038/s41429-024-00737-z","url":null,"abstract":"A new polyene macrolide, machidamycin (1), and a known compound YS-822A (2), were obtained by physicochemical screening from a culture broth of Streptomyces sp. K22-0017. The structures were elucidated using MS and 1D/2D NMR analyses. Compound 1 exhibited weak antifungal activity against Candida albicans and Mucor racemosus. Furthermore, 1 showed stronger antileishmanial activity than the existing drug paromomycin.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"540-543"},"PeriodicalIF":2.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946466","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}

{"title":"Paranazzamides A and B, new cyclic dipeptides containing a C7-prenylated tryptophan, produced by pathogenic reptile fungi Paranannizziopsis sp. UH-21","authors":"Keisuke Kobayashi, Rio Tejima, Kenichiro Nagai, Reiko Seki, Tsuyoshi Hosoya, Yumi Une, Satoru Shigeno, Hiroshi Tomoda, Taichi Ohshiro","doi":"10.1038/s41429-024-00725-3","DOIUrl":"10.1038/s41429-024-00725-3","url":null,"abstract":"Two new cyclic dipeptides, paranazzamides A (1) and B (2) containing a C7-prenylated tryptophan, were isolated from a culture broth of snake fungal disease-isolate Paranannizziopsis sp. UH-21. This is the first report on the new secondary metabolites from Paranannizziopsis sp. The planar structures of 1 and 2 were elucidated using various spectroscopic techniques including MS and 1D/2D NMR. The absolute configuration of 1 was assigned by comparison with the synthesized compound. Compounds 1 and 2 exhibited no antifungal activity, no antibacterial activity, and no cytotoxic activity even at a concentration of 128 µg ml−1, whereas 1 and 2 exhibited amphotericin B potentiating activity against Candida auris in combination treatment.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 7","pages":"403-411"},"PeriodicalIF":2.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00725-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946469","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}

{"title":"Synergistic anti-virulence efficacy of citral and carvacrol against mixed vaginitis causing Candida albicans and Gardnerella vaginalis: An in vitro and in vivo study","authors":"Ravi Jothi, Shanmugaraj Gowrishankar","doi":"10.1038/s41429-024-00728-0","DOIUrl":"10.1038/s41429-024-00728-0","url":null,"abstract":"Mixed vaginitis due to bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) is the most prevalent form and presents a significant therapeutic challenge globally. Since, the administration of monotherapy leads to subsequent recurrent infections, synergistic therapy that completely eradicates both pathogens is of dire need to manage mixed vaginities scenario and to prevent its recurrence. The current investigation was focused on exploring the synergistic inhibitory efficacy of phytochemicals against the virulence traits of individual and mixed species of C. albicans and G. vaginalis in vitro and in vivo (Galleria mellonella). Out of five phytochemicals (carvacrol, thymol, cinnamaldehyde, eugenol, and borneol) screened for synergism with citral [(Ct) as the prime molecule owing to its myriad therapeutic potential], carvacrol (Ca) in combination with citral exhibited promising synergistic effect. Time-kill kinetics and one-minute contact-killing assays demonstrated the phenomenal microbicidal effect of Ct-Ca combination against both mono and dual-species within 30 min and one-minute time intervals, respectively. Furthermore, the sub-CMICs (synergistic combinatorial MIC) of Ct-Ca have significantly eradicated the mature biofilms and remarkably reduced the virulence attributes of both C. albicans and G. vaginalis (viz., yeast to hyphae transition, filamentation, protease production, and hydrophobicity index), in single and dual species states. The non-toxic nature of Ct-Ca combination was authenticated using in vitro (human erythrocyte cells) and in vivo (Galleria mellonella) models. In addition, the in vivo efficacy evaluation and subsequent histopathological investigation was done using the invertebrate model system G. mellonella, which further ascertained the effectiveness of Ct-Ca combination in fighting off the infection caused by individual and mixed species of C. albicans and G. vaginalis. Concomitantly, the current work is the first of its kind to delineate the in vitro interaction of C. albicans and G. vaginalis mixed species at their growth and biofilm states, together emphasizes the promising therapeutic potential of acclaimed phytochemicals as combinatorial synergistic therapy against mixed vaginitis","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 7","pages":"436-453"},"PeriodicalIF":2.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946471","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}

{"title":"Quinomycins with an unusual N-methyl-3-methylsulfinyl-alanine residue from a Streptomyces sp","authors":"Anqi Wang, Shasha Li, Yuanjuan Wei, Guiyang Wang, Wenjing Shi, Yue Shang, Liyan Yu, Shuzhen Chen, Yan Li, Maoluo Gan","doi":"10.1038/s41429-024-00736-0","DOIUrl":"10.1038/s41429-024-00736-0","url":null,"abstract":"Four new echinomycin congeners, quinomycins M−P (1−4) were isolated from the cultures of the soil-derived Streptomyces sp. CPCC205575. The planar structures were determined by comprehensive analyses of NMR and HRESIMS/MS data. The absolute configurations were elucidated by the advanced Marfey’s method combined with biosynthetic gene analysis. Compounds 1−4 represent the first examples of quinomycin-type natural products with the sulfur atom at the N,S-dimethylcysteine residue oxidized as a sulfoxide group forming the unusual N-methyl-3-methylsulfinyl-alanine residue. Bioassay results revealed that the oxidation of the sulfur atom at the Cys or Cys′ residues led to dramatic decrease of cytotoxicity and antimicrobial activity.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"506-514"},"PeriodicalIF":2.1,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923816","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}

{"title":"Chalcomoracin promotes apoptosis and endoplasmic reticulum stress in hepatocellular carcinoma cells","authors":"Yongliang Cui, Liqin Lan, Jiahui Lv, Bixing Zhao, Jinfeng Kong, Yongping Lai","doi":"10.1038/s41429-024-00732-4","DOIUrl":"10.1038/s41429-024-00732-4","url":null,"abstract":"Chalcomoracin (CMR), a Diels-Alder adduct obtained from mulberry leaves, demonstrated wide-spectrum anti-cancer activity. Herein, we aimed to explore the function of CMR and how it works in hepatocellular carcinoma (HCC). Human HCC cell lines Hep3B and SNU-387 were cultured and treated with various concentrations of CMR (1.5, 3, and 6 µM). Subsequently, the effects of CMR on cell viability, colony formation, apoptosis, migration, and invasion abilities were studied in vitro. Furthermore, the levels of endoplasmic reticulum (ER) stress-related proteins and mitogen-activated protein kinase (MAPK) pathway-related proteins in cells under CMR exposure were detected using western blot. Experiments in vivo were conducted to examine the effects of CMR on tumor growth in HCC. CMR administration inhibited the viability and clonogenic, migration, and invasion abilities, as well as promoted cell apoptosis and ER stress in Hep3B and SNU-387 cells. In addition, CMR treatment reduced the phosphorylation levels of ERK, P38, and JNK in the MAPK pathway. Moreover, an in vivo study showed that CMR administration could inhibit tumorigenesis and MAPK pathway activity in HCC. Our data indicate that CMR has the potential to inhibit the development of HCC, potentially through the inhibition of the MAPK pathway. These findings suggest that CMR may have promising applications as an anticancer agent in future therapeutics for HCC.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 7","pages":"428-435"},"PeriodicalIF":2.1,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900350","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}