Concerning the requirements of effective drug candidates to combat against high rising multidrug resistant pathogens, we isolated three new linear lipopeptides, gageostatins A–C (1–3), consisting of hepta-peptides and new 3-β-hydroxy fatty acids from the fermentation broth of a marine-derived bacterium Bacillus subtilis. Their structures were elucidated by analyzing a combination of extensive 1D, 2D NMR spectroscopic data and high resolution ESIMS data. Fatty acids, namely 3-β-hydroxy-11-methyltridecanoic and 3-β-hydroxy-9,11-dimethyltridecanoic acids were characterized in lipopeptides 1 and 2, respectively, whereas an unsaturated fatty acid (E)-7,9-dimethylundec-2-enoic acid was assigned in 3. The 3R configuration of the stereocenter of 3-β-hydroxy fatty acids in 1 and 2 was established by Mosher’s MTPA method. The absolute stereochemistry of amino acid residues in 1–3 was ascertained by acid hydrolysis followed by Marfey’s derivatization studies. Gageostatins 1–3 exhibited good antifungal activities with MICs values of 4–32 µg/mL when tested against pathogenic fungi (R. solani, B. cinerea and C. acutatum) and moderate antibacterial activity against bacteria (B. subtilis, S. aeureus, S. typhi and P. aeruginosa) with MICs values of 8–64 µg/mL. Futhermore, gageostatins 1–3 displayed cytotoxicity against six human cancer cell lines with GI50 values of 4.6–19.6 µg/mL. It is also noteworthy that mixed compounds 1+2 displayed better antifungal and cytotoxic activities than individuals.
Gageotetrins A-C (1-3), a unique class of linear lipopeptides, consisting of di- and tetrapeptides and a new fatty acid were isolated from a Marine Bacillus subtilis. The structures of 1-3 were assigned by spectroscopic data and their absolute stereochemistries were ascertained by chemical derivatization. Compounds 1-3 displayed good antimicrobial activities with MIC values of 0.01-0.06 μM. However, these compounds failed to register any cytotoxicity (GI50 > 30 μg/ml) against human cancer cell lines.
Wheat blast is a devastating fungal disease caused by a filamentous fungus, Magnaporthe oryzae Triticum (MoT) pathotype, which poses a serious threat to food security of South America and South Asia. In the course of screening novel bioactive secondary metabolites, we found that some secondary metabolites from a marine Bacillus subtilis strain 109GGC020 remarkably inhibited the growth of M. oryzae Triticum in vitro at 20 µg/disk. We tested a number of natural compounds derived from microorganisms and plants and found that five recently discovered linear noncytotoxic lipopeptides, gageopeptides A-D (1-4) and gageotetrin B (5) from the strain 109GGC020 inhibited the growth of MoT mycelia in a dose-dependent manner. Among the five compounds studied, gageotetrin B (5) displayed the highest mycelial growth inhibition of MoT followed by gageopeptide C (3), gageopeptide D (4), gageopeptide A (1), and gageopeptide B (2) with minimum inhibitory concentrations (MICs) of 1.5, 2.5, 2.5, 10.0, and 10.0 µg/disk, respectively. Application of these natural compounds has also completely blocked formation of conidia in the MoT fungal mycelia in the agar medium. Further bioassay revealed that these compounds (1-5) inhibited the germination of MoT conidia and, if germinated, induced deformation of germ tube and/or abnormal appressoria. Interestingly, application of these linear lipopeptides (1-5) significantly suppressed wheat blast disease on detached wheat leaves. This is the first report of the inhibition of mycelial growth, conidiogenesis, conidial germination, and morphological alterations in the germinated conidia and suppression of wheat blast disease by linear lipopeptides from the strain of B. subtilis. A further study is needed to evaluate the mode of action of these natural compounds for considering them as biopesticides for managing this notorious cereal killer.
ObjectiveEndophytes have the potential to synthesize various bioactive secondary metabolites. The aim of the study was to find new cytotoxic and antibacterial metabolites from endophytic fungus, Cladosporium sp. isolated from the leaves of Rauwolfia serpentina (L.) Benth. ex Kurz. (Fam: Apocyanaceae).Materials and methodsThe endophytic fungus was grown on potato dextrose agar medium and extracted using ethyl acetate. Secondary metabolites were isolated by chromatographic separation and re-crystallization, and structures were confirmed by 1H NMR, 13C NMR and mass spectroscopic data. The cytotoxicity was determined by WST-1 assay and brine shrimp lethality bioassay, while antibacterial activity was assessed by disc diffusion method.ResultsTwo naphthoquinones, namely anhydrofusarubin (1) and methyl ether of fusarubin (2), were isolated from Cladosporium sp. The isolated compounds 1 and 2, by WST-1 assay against human leukemia cells (K-562) showed potential cytotoxicity with IC50 values of 3.97 μg/mL and 3.58 μg/mL, respectively. Initial screening of crude ethyl acetate extract and column fractions F-8 and F-10 exhibited noticeable cytotoxicity to brine shimp nauplii with LC50 values of 42.8, 1.2 and 2.1 μg/mL, respectively. Moreover, the isolated compound 2 (40 μg/disc) showed prominent activities against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus megaterium with an average zone of inhibition of 27 mm, 25 mm, 24 mm and 22 mm, respectively and the activities were compared with kanamycin (30 μg/disc).ConclusionOur findings indicate that anhydrofusarubin (1) and methyl ether of fusarubin (2) might be useful lead compounds to develop potential cytotoxic and antimicrobial drugs.
Marine bacteria are a potential source of structurally diversified bioactive secondary metabolites that are not found in terrestrial sources. In our continuous effort to search for new antimicrobial agents from marine-derived bacteria, we isolated bacterial strain 109GGC020 from a marine sediment sample collected from Gageocho, Republic of Korea. The strain was identified as Bacillus subtilis based on a 16s rRNA sequence analysis. After a 7-day fermentation of the B. subtilis strain under optimum growth conditions three new and four known secondary metabolites were discovered using chromatographic procedures, and their biological activities were evaluated against both bacteria and crop-devastating fungi. The discovered metabolites were confirmed by extensive 2D NMR and high-resolution ESI-MS data analyses to have the structures of new macrolactin derivatives gageomacrolactins 1-3 and known macrolactins A (4), B (5), F (6), and W (7). The stereoconfigurations of 1-3 were assigned based on coupling constant values, chemical derivatization studies, and a literature review. The coupling constants were very crucial to determine the relative geometries of olefins in 1-3 because of overlap of the ¹H NMR signals. The NMR data of these compounds were recorded in different solvents to overcome this problem and obtain accurate coupling constant values. The new macrolactin derivatives 1-3 displayed good antibiotic properties against both Gram-positive (S. aureus, B. subtilis, and B. cereus) and Gram-negative (E. coli, S. typhi, and P. aeruginosa) bacteria with minimum inhibitory concentration (MIC) values of 0.02-0.05 μM. Additionally, the antifungal activities of 1-7 were evaluated against pathogenic fungi and found to inhibit mycelial growth of A. niger, B. cinerea, C. acutatum, C. albicans, and R. solani with MIC values of 0.04-0.3 μM, demonstrating that these compounds were good fungicides.
Bioassay-guided isolation of bioactive metabolites from the ethyl acetate extract of a marine Bacillus sp. fermentation broth has led to the discovery of three new 24-membered macrolactones, macrolactins 1-3, which contain an oxetane, an epoxide, and a tetrahydropyran ring, respectively. The configurations of 1-3 were assigned by a combination of coupling constants, ROESY data analysis, and application of the modified Mosher's method. Compounds 1-3 showed in vitro antimicrobial activity.
Antioxidants have been widely studied in the fields of biology, medicine, food, and nutrition sciences. There has been extensive work on developing assays for foods and biological systems. The scientific communities have well-accepted the effectiveness of endogenous antioxidants generated in the body. However, the health efficacy and the possible action of exogenous dietary antioxidants are still questionable. This may be attributed to several factors, including a lack of basic understanding of the interaction of exogenous antioxidants in the body, the lack of agreement of the different antioxidant assays, and the lack of specificity of the assays, which leads to an inability to relate specific dietary antioxidants to health outcomes. Hence, there is significant doubt regarding the relationship between dietary antioxidants to human health. In this review, we documented the variations in the current methodologies, their mechanisms, and the highly varying values for six common food substrates (fruits, vegetables, processed foods, grains, legumes, milk, and dairy-related products). Finally, we discuss the strengths and weaknesses of the antioxidant assays and examine the challenges in correlating the antioxidant activity of foods to human health.
Ieodoglucomides A (1) and B (2), unique glycolipopeptides consisting of an amino acid, a new fatty acid, a succinic acid, and a sugar, were isolated from a Marine-derived bacterium Bacillus licheniformis. The absolute stereochemistry of 1 and 2 was determined by deploying coupling constants, Marfey's and Mosher's methods, and literature reviews. Compounds 1 and 2 displayed moderate in vitro antimicrobial activity. Furthermore, ieodoglucomide B (2) exhibited cytotoxic activity against lung cancer and stomach cancer cell lines with GI 50 values of 25.18 and 17.78 μg/mL, respectively.
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