Gageostatins A–C,Antimicrobial Linear Lipopeptides from a Marine Bacillus subtilis

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.     

Antimicrobial Activity of the Marine Alkaloids,Clathrodin and Oroidin,and Their Synthetic Analogues

Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds for the design and synthesis of novel bioactive compounds. The marine alkaloids, clathrodin and oroidin, which were originally isolated from sponges of the genus, Agelas, were prepared and evaluated for their antimicrobial activity against three bacterial strains (Enterococcus faecalis, Staphylococcus aureus and Escherichia coli) and one fungal strain (Candida albicans), and oroidin was found to possess promising Gram-positive antibacterial activity. Using oroidin as a scaffold, 34 new analogues were designed, prepared and screened for their antimicrobial properties. Of these compounds, 12 exhibited >80% inhibition of the growth of at least one microorganism at a concentration of 50 µM. The most active derivative was found to be 4-phenyl-2-aminoimidazole 6h, which exhibited MIC₉₀ (minimum inhibitory concentration) values of 12.5 µM against the Gram-positive bacteria and 50 µM against E. coli. The selectivity index between S. aureus and mammalian cells, which is important to consider in the evaluation of a compound’s potential as an antimicrobial lead, was found to be 2.9 for compound 6h.     

Antimicrobial Diterpene Alkaloids from an Agelas citrina Sponge Collected in the Yucatán Peninsula

Three new diterpene alkaloids, (+)-8-epiagelasine T (1), (+)-10-epiagelasine B (2), and (+)-12-hydroxyagelasidine C (3), along with three known compounds, (+)-ent-agelasine F (4), (+)-agelasine B (5), and (+)-agelasidine C (6), were isolated from the sponge Agelas citrina, collected on the coasts of the Yucatán Peninsula (Mexico). Their chemical structures were elucidated by 1D and 2D NMR spectroscopy, HRESIMS techniques, and a comparison with literature data. Although the synthesis of (+)-ent-agelasine F (4) has been previously reported, this is the first time that it was isolated as a natural product. The evaluation of the antimicrobial activity against the Gram-positive pathogens Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis showed that all of them were active, with (+)-10-epiagelasine B (2) being the most active compound with an MIC in the range of 1–8 µg/mL. On the other hand, the Gram-negative pathogenes Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were also evaluated, and only (+)-agelasine B (5) showed a moderate antibacterial activity with a MIC value of 16 μg/mL.     

Talaromarins A–F: Six New Isocoumarins from Mangrove-Derived Fungus Talaromyces flavus TGGP35

Six new isocoumarin derivative talaromarins A-F (1–6), along with 17 known analogues (7–23), were isolated from the mangrove-derived fungus Talaromyces flavus (Eurotiales: Trichocomaceae) TGGP35. Their structures were identified by detailed IR, UV, 1D/2D NMR and HR-ESI-MS spectra. The absolute configurations of new compounds were determined by the modified Mosher’s method and a comparison of their CD spectra with dihydroisocoumarins described in the literature. The antioxidant, antibacterial, anti-phytopathogenic and inhibitory activity against α-glucosidase of all the isolated compounds were tested. Compounds 6–11, 17–19 and 21–22 showed similar or better antioxidant activity than the IC₅₀ values ranging from 0.009 to 0.27 mM, compared with the positive control trolox (IC₅₀ = 0.29 mM). Compounds 10, 18, 21 and 23 exhibited strong inhibitory activities against α-glucosidase with IC₅₀ values ranging from 0.10 to 0.62 mM, while the positive control acarbose had an IC₅₀ value of 0.5 mM. All compounds showed no antibacterial or anti-phytopathogenic activity at the concentrations of 50 μg/mL and 1 mg/mL, respectively. These results indicated that isocoumarins will be useful to developing antioxidants and as diabetes control agents.     

New Furan and Cyclopentenone Derivatives from the Sponge-Associated Fungus Hypocrea Koningii PF04

Two new furan derivatives, hypofurans A and B (1 and 2), and three new cyclopentenone derivatives, hypocrenones A–C (3–5), along with seven known compounds (6–12), were isolated from a marine fungus Hypocrea koningii PF04 associated with the sponge Phakellia fusca. Among them, compounds 10 and 11 were obtained for the first time as natural products. The planar structures of compounds 1–5 were elucidated by analysis of their spectroscopic data. Meanwhile, the absolute configuration of 1 was determined as 2R,3R by the comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. All the isolates were evaluated for their antibacterial and antioxidant activity. Compounds 1, 10, and 12 all showed modest antibacterial activity against Staphylococcus aureus ATCC25923 (MIC, 32 μg/mL). In addition, compounds 1, 10 and 11 exhibited moderate DPPH radical scavenging capacity with IC₅₀ values of 27.4, 16.8, and 61.7 µg/mL, respectively.     

Anthraquinones,Diphenyl Ethers,and Their Derivatives from the Culture of the Marine Sponge-Associated Fungus Neosartorya spinosa KUFA 1047

Previously unreported anthraquinone, acetylpenipurdin A (4), biphenyl ether, neospinosic acid (6), dibenzodioxepinone, and spinolactone (7) were isolated, together with (R)-6-hydroxymellein (1), penipurdin A (2), acetylquestinol (3), tenellic acid C (5), and vermixocin A (8) from the culture of a marine sponge-associated fungus Neosartorya spinosa KUFA1047. The structures of the previously unreported compounds were established based on an extensive analysis of 1D and 2D NMR spectra as well as HRMS data. The absolute configurations of the stereogenic centers of 5 and 7 were established unambiguously by comparing their calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 2 and 5–8 were tested for their in vitro acetylcholinesterase and tyrosinase inhibitory activities as well as their antibacterial activity against Gram-positive and Gram-negative reference, and multidrug-resistant strains isolated from the environment. The tested compounds were also evaluated for their capacity to inhibit biofilm formation in the reference strains.     

Diverse Secondary Metabolites from the Coral-Derived Fungus Aspergillus hiratsukae SCSIO 5Bn1003

Three new metabolites, including a cyclic tetrapeptide asperhiratide (1), an ecdysteroid derivative asperhiratine (2), and a sesquiterpene lactone asperhiratone (3), were isolated and identified from the soft coral-derived fungus Aspergillus hiratsukae SCSIO 5Bn₁003, together with 10 known compounds. Their structures were elucidated via spectroscopic analysis, X-ray diffraction analysis, and electronic circular dichroism calculations. In addition, the absolute configuration of 1 was determined by Marfey’s technique and an analysis of the acid hydrolysates using a chiral phase HPLC column. Among all the compounds, 6 and 8 showed medium cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), with IC₅₀ values ranging from 31.03 ± 3.04 to 50.25 ± 0.54 µM. Meanwhile, they strongly inhibited α-glucosidase activities, with IC₅₀ values of 35.73 ± 3.94 and 22.00 ± 2.45 µM, which were close to and even stronger than the positive control acarbose (IC₅₀ = 32.92 ± 1.03 µM). Compounds 6–8 showed significant antibacterial activities against Bacillus subtilis, with MIC values of 10.26 ± 0.76 µM, 17.00 ± 1.25 µM, and 5.30 ± 0.29 µM, respectively. Compounds 9 and 12 exhibited potent radical scavenging activities against DPPH, with IC₅₀ values of 12.23 ± 0.78 µM and 7.38 ± 1.16 µM. In addition, asperhiratide (1) was evaluated for anti-angiogenic activities in the in vivo zebrafish model, which showed a weak inhibitory effect on intersegmental vessel (ISV) formation.     

Cytoskyrins and cytosporones produced by Cytospora sp. CR200: taxonomy, fermentation and biological activities

In screening endophytic fungi from Costa Rica for bioactivity, fungal culture CR200, isolated from a buttonwood tree, was found to contain compounds that initiate DNA damage in a test strain of E. coli (Biochemical Induction Assay, BIA) and inhibit growth of Gram-positive bacteria, including antibiotic-resistant strains. Two new bisanthraquinones (cytoskyrins A and B) and five new related octaketides (cytosporones A-E) were isolated from fermentation broths of this fungus. Cytoskyrin A exhibited potent in-vitro antibacterial (MICs against Gram-positive bacteria, 0.03 – 0.25 μg/mL) and DNA-damaging activities (10 ng/spot), whereas cytoskyrin B was inactive in these assays. Among the cytosporones, only D and E exhibited Gram-positive activity, but they were inactive in the BIA. Mechanistically, cytoskyrin A specifically inhibited DNA synthesis in E. coli imp at its MIC; however, it also moderately inhibited protein synthesis at 2x its MIC. Cytoskyrin A exhibited poor cytotoxicity against tumor cell lines (IC₅₀ > 5 μg/mL) compared to known antitumor agents. The nuclear ribosomal internal transcribed spacer region of CR200 was found to share highest similarity (94–96%) with Cytospora spp. Micro- and macroscopic morphological observations of the conidia and conidiomata, respectively, also suggested this fungus to be a Cytospora sp.     

Xishaeleganins A–D,Sesquiterpenoid Hydroquinones from Xisha Marine Sponge Dactylospongia elegans

Four new sesquiterpene hydroquinones, xishaeleganins A–D (6–9), along with eleven known related ones (12 and 14–23) were isolated from the Xisha marine sponge Dactylospongia elegans (family Thorectida). Their structures were determined by extensive spectroscopic analysis, ECD calculations, and by comparison with the spectral data reported in the literature. Compounds 7, 15, 20, and 21 showed significant antibacterial activity against Staphylococcus aureus, with minimum inhibitory concentration values of 1.5, 2.9, 5.6, and 5.6 µg/mL, which are comparable with those obtained for the positive control vancomycin (MIC: 1.0 µg/mL).     

Antibacterial and Antibiofilm Activities of Tryptoquivalines and Meroditerpenes Isolated from the Marine-Derived Fungi Neosartorya paulistensis,N. laciniosa,N. tsunodae,and the Soil Fungi N. fischeri and N. siamensis

A new meroditerpene, sartorypyrone C (5), was isolated, together with the known tryptoquivalines l (1a), H (1b), F (1c), 3′-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5′]-2,2′-dione (2) and 4(3H)-quinazolinone (3), from the culture of the marine sponge-associated fungus Neosartorya paulistensis (KUFC 7897), while reexamination of the fractions remaining from a previous study of the culture of the diseased coral-derived fungus N. laciniosa (KUFC 7896) led to isolation of a new tryptoquivaline derivative tryptoquivaline T (1d). Compounds 1a–d, 2, 3, and 5, together with aszonapyrones A (4a) and B (4b), chevalones B (6) and C (7a), sartorypyrones B (7b) and A (8), were tested for their antibacterial activity against four reference strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa), as well as the environmental multidrug-resistant isolates. Only aszonapyrone A (4a) and sartorypyrone A (8) exhibited significant antibacterial activity as well as synergism with antibiotics against the Gram-positive multidrug-resistant strains. Antibiofilm assays of aszonapyrone A (4a) and sartorypyrone A (8) showed that practically no biofilm was formed in the presence of their 2× MIC and MIC. However, the presence of a sub-inhibitory concentration of ½ MIC of 4a and 8 was found to increase the biofilm production in both reference strain and the multidrug-resistant isolates of S. aureus.     

Butremycin,the 3-Hydroxyl Derivative of Ikarugamycin and a Protonated Aromatic Tautomer of 5′-Methylthioinosine from a Ghanaian Micromonospora sp. K310

A new actinomycete strain Micromonospora sp. K310 was isolated from Ghanaian mangrove river sediment. Spectroscopy-guided fractionation led to the isolation of two new compounds from the fermentation culture. One of the compounds is butremycin (2) which is the (3-hydroxyl) derivative of the known Streptomyces metabolite ikarugamycin (1) and the other compound is a protonated aromatic tautomer of 5′-methylthioinosine (MTI) (3). Both new compounds were characterized by 1D, 2D NMR and MS data. Butremycin (2) displayed weak antibacterial activity against Gram-positive S. aureus ATCC 25923, the Gram-negative E. coli ATCC 25922 and a panel of clinical isolates of methicillin-resistant S. aureus (MRSA) strains while 3 did not show any antibacterial activity against these microbes.     

Butenolides from the Coral-Derived Fungus Aspergillius terreus SCSIO41404

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (−)-asperteretal G (1b), (+)-asperteretal H (2a), (−)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4–13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC₅₀ = 25 μg/mL) and Klebsiella pneumoniae (IC₅₀ = 50 μg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2–73.0% at a concentration of 50 μg/mL.     

Metabolic Profiling and In Vitro Assessment of the Biological Activities of the Ethyl Acetate Extract of Penicillium chrysogenum “Endozoic of Cliona sp. Marine Sponge” from the Red Sea (Egypt)

Marine sponge-derived endozoic fungi have been gaining increasing importance as promising sources of numerous and unique bioactive compounds. This study investigates the phytochemical profile and biological activities of the ethyl acetate extract of Penicillium chrysogenum derived from Cliona sp. sponge. Thirty-six compounds were tentatively identified from P. chrysogenum ethyl acetate extract along with the kojic acid (KA) isolation. The UPLC-ESI-MS/MS positive ionization mode was used to analyze and identify the extract constituents while 1D and 2D NMR spectroscopy were used for kojic acid (KA) structure confirmation. The antimicrobial, antioxidant, and cytotoxic activities were assessed in vitro. Both the extract and kojic acid showed potent antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa with MIC 250 ± 0.82 µg/mL. Interestingly, the extract showed strong antifungal activity against Candida albicans and Cryptococcus neoformans with MIC 93.75 ± 0.55 and 19.53 ± 0.48 µg/mL, respectively. Furthermore, KA showed the same potency against Fusarium oxysporum and Cryptococcus neoformans with MIC 39.06 ± 0.85 and 39.06 ± 0.98 µg/mL, respectively. Ultimately, KA showed strong antioxidant activity with IC₅₀ 33.7 ± 0.8 µg/mL. Moreover, the extract and KA showed strong cytotoxic activity against colon carcinoma (with IC₅₀ 22.6 ± 0.8 and 23.4 ± 1.4 µg/mL, respectively) and human larynx carcinoma (with equal IC₅₀ 30.8 ± 1.3 and ± 2.1 µg/mL, respectively), respectively. The current study represents the first insights into the phytochemical profile and biological properties of P. chrysoenum ethyl acetate extract, which could be a promising source of valuable secondary metabolites with potent biological potentials.     

Targeted Isolation of Antibiotic Brominated Alkaloids from the Marine Sponge Pseudoceratina durissima Using Virtual Screening and Molecular Networking

Many targeted natural product isolation approaches rely on the use of pre-existing bioactivity information to inform the strategy used for the isolation of new bioactive compounds. Bioactivity information can be available either in the form of prior assay data or via Structure Activity Relationship (SAR) information which can indicate a potential chemotype that exhibits a desired bioactivity. The work described herein utilizes a unique method of targeted isolation using structure-based virtual screening to identify potential antibacterial compounds active against MRSA within the marine sponge order Verongiida. This is coupled with molecular networking-guided, targeted isolation to provide a novel drug discovery procedure. A total of 12 previously reported bromotyrosine-derived alkaloids were isolated from the marine sponge species Pseudoceratina durissima, and the compound, (+)-aeroplysinin-1 (1) displayed activity against the MRSA pathogen (MIC: <32 µg/mL). The compounds (1–3, 6 and 9) were assessed for their central nervous system (CNS) interaction and behavioral toxicity to zebrafish (Danio rerio) larvae, whereby several of the compounds were shown to induce significant hyperactivity. Anthelmintic activity against the parasitic nematode Haemonchus contorutus was also evaluated (2–4, 6–8).     

Polyketides and Meroterpenes from the Marine-Derived Fungi Aspergillus unguis 158SC-067 and A. flocculosus 01NT-1.1.5 and Their Cytotoxic and Antioxidant Activities

Ten secondary metabolites, including a new grifolin analog, grifolin B (1); a new homovalencic acid derivative, 12-hydroxyhomovalencic acid (7); and a compound isolated from a natural source for the first time (9), along with seven known compounds, grifolin (2), averantin (3), 7-chloroaverantin (4), 1′-O-methylaverantin (5), 7-hydroxy-2-(2-hydroxypropyl)-5-pentylchromone (6), homovalencic acid (8), and bekeleylactone E (10), were isolated from two fungal strains. The structures of 1–10 were identified by detailed analysis and comparison of their spectroscopic data with literature values. Compounds 9 and 10 showed moderate cytotoxic activity against a panel of cancer cell lines (PC-3, HCT-15, MDA-MB-231, ACHN, NCI-H23, NUGC-3), with the GI₅₀ values ranging from 1.1 µM to 3.6 µM, whereas 1 displayed a weak 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity without cytotoxicity against all tested cell lines.     

Antimicrobial Terpenoids from South China Sea Soft Coral Lemnalia sp.

Chemical investigation of the South China Sea soft coral Lemnalia sp. afforded 13 structurally diverse terpenoids, including three new neolemnane sesquiterpene lineolemnenes E–G (1–3); a new aristolane-type sesquiterpenoid, 2-acetoxy-aristolane (4); four new decalin-type bicyclic diterpenes, named biofloranates A−D (5−8); a new serrulatane, named euplexaurene D (9); and a new aromadendrane-type diterpenoid cneorubin K (10), together with three known related compounds (11−13). The structures of the new compounds were elucidated by NMR spectroscopy, the Mosher’s method, and ECD analysis. Compounds 1–13 were tested in a wide panel of biological assays. Lineolemnene J (3) showed weak cytotoxicity against the CCRF-CEM cancer cell line. The isolated new diterpenes, except euplexaurene D (9), demonstrated moderate antimicrobial activity against Bacillus subtilis and Staphylococcus aureus with a MIC of 4−64 μg/mL. Compound 2 exhibited a mild inhibitory effect against influenza A H1N1 virus (IC₅₀ = 5.9 µM).     

New Sorbicillinoids with Tea Pathogenic Fungus Inhibitory Effect from Marine-Derived Fungus Hypocrea jecorina H8

Four new dimeric sorbicillinoids (1–3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6–11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from mangrove sediment, and showed potent inhibitory activity against the tea pathogenic fungus Pestalotiopsis theae (P. theae). The planar structures of 1–5 were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus P. theae. Compounds 5, 6, 8, 9, and 10 exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED₅₀ of 24.25 ± 1.57 µg/mL. The ED₅₀ values of compounds 5, 6, 8, 9, and 10 were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds 5 and 8, which imparted toxic effects on zebrafish even at 0.625 μM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (6, 9, and 10) from H. jecorina H8 displayed low toxicity and high anti-tea pathogenic fungus potential.     

Anti-Mycobacterial Nucleoside Antibiotics from a Marine-Derived Streptomyces sp. TPU1236A

Five new nucleoside antibiotics, named streptcytosines A–E (1–5), and six known compounds, de-amosaminyl-cytosamine (6), plicacetin (7), bamicetin (8), amicetin (9), collismycin B (10), and SF2738 C (11), were isolated from a culture broth of Streptomyces sp. TPU1236A collected in Okinawa, Japan. The structures of new compounds were elucidated on the basis of their spectroscopic data (HRFABMS, IR, UV, and 2D NMR experiments including ¹H-¹H COSY, HMQC, HMBC, and NOESY spectra). Streptcytosine A (1) belonged to the amicetin group antibiotics, and streptcytosines B–E (2–5) were derivatives of de-amosaminyl-cytosamine (6), 2,3,6-trideoxyglucopyranosyl cytosine. Compound 1 inhibited the growth of Mycobacterium smegmatis (MIC = 32 µg/mL), while compounds 2–5 were not active at 50 µg/disc. Bamicetin (8) and amicetin (9) showed the MICs of 16 and 8 µg/mL, respectively.     

Six New Diterpene Glycosides from the Soft Coral Lemnalia bournei

A chemical study on the extracts of soft coral Lemnalia bournei resulted in the isolation and identification of six new bicyclic diterpene glycosides including three new lemnaboursides E–G (1–3), and three new lemnadiolboursides A–C (4–6), along with three known lemnaboursides (7–9). Their structures were elucidated by detailed spectroscopic analysis, ECD analysis, chemical methods, and comparison with the literature data. Lemnadiolboursides A–C (4–6) contained a lemnal-1(10)-ene-7,12-diol moiety compared with the lemnaboursides. All these compounds were evaluated for antibacterial activity; cell growth inhibition of A549, Hela, HepG2, and CCRF-CEM cancer cell lines; and inhibition of LPS-induced NO production in RAW264.7 macrophages. The results indicated that compounds 1, 2, and 4–6 exhibited antibacterial activity against Staphylococcus aureus and Bacillus subtilis (MIC 4–16 μg/mL); compounds 1–9 displayed low cytotoxicity on the CCRF-CEM cell lines (IC₅₀ 10.44–27.40 µM); and compounds 1, 2, and 5 showed weak inhibition against LPS-induced NO production (IC₅₀ 21.56–28.06 μM).     

Antibacterial and Cytotoxic New Napyradiomycins from the Marine-Derived Streptomyces sp. SCSIO 10428

Three new napyradiomycins (1–3) were isolated from the culture broth of a marine-derived actinomycete strain SCSIO 10428, together with six known related analogues napyradiomycin A1 (4), 18-oxonapyradiomycin A1 (5), napyradiomycin B1 (6), napyradiomycin B3 (7), naphthomevalin (8), and napyradiomycin SR (9). The strain SCSIO 10428 was identified as a Streptomyces species by the sequence analysis of its 16S rRNA gene. The structures of new compounds 1–3, designated 4-dehydro-4a-dechloronapyradiomycin A1 (1), 3-dechloro-3-bromonapyradiomycin A1 (2), and 3-chloro-6,8-dihydroxy-8-α-lapachone (3), respectively, were elucidated by comparing their 1D and 2D NMR spectroscopic data with known congeners. None of the napyradiomycins 1–9 showed antioxidative activities. Napyradiomycins 1–8 displayed antibacterial activities against three Gram-positive bacteria Staphylococcus and Bacillus strains with MIC values ranging from 0.25 to 32 μg mL⁻¹, with the exception that compound 3 had a MIC value of above 128 μg mL⁻¹ against Staphylococcus aureus ATCC 29213. Napyradiomycins 2, 4, 6, and 7 exhibited moderate cytotoxicities against four human cancer cell lines SF-268, MCF-7, NCI-H460, and HepG-2 with IC₅₀ values below 20 μM, while the IC₅₀ values for other five napyradiomycins 1, 3, 5, 8 and 9 were above 20 μM.