Violapyrones H and I,New Cytotoxic Compounds Isolated from Streptomyces sp. Associated with the Marine Starfish Acanthaster planci

Two new α-pyrone derivatives, violapyrones H (1) and I (2), along with known violapyrones B (3) and C (4) were isolated from the fermentation broth of a marine actinomycete Streptomyces sp. The strain was derived from a crown-of-thorns starfish, Acanthaster planci, collected from Chuuk, Federated States of Micronesia. The structures of violapyrones were elucidated by the analysis of 1D and 2D NMR and HR-ESIMS data. Violapyrones (1–4) exhibited cytotoxicity against 10 human cancer cell lines with GI₅₀ values of 1.10–26.12 μg/mL when tested using sulforhodamine B (SRB) assay. This is the first report on the cytotoxicity of violapyrones against cancer cell lines and the absolute configuration of violapyrone C.     

Rare Carbon-Bridged Citrinin Dimers from the Starfish-Derived Symbiotic Fungus Penicillium sp. GGF16-1-2

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G–J (1–4), and five known analogs (5–9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1–9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD₅₀ values from 0.61 μg/mL to 16.14 μg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3).     

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.     

Polyhydroxylated Steroids from the South China Sea Soft Coral Sarcophyton sp. and Their Cytotoxic and Antiviral Activities

Chemical investigation on the soft coral Sarcophyton sp. collected from the South China Sea yielded three new polyhydroxylated steroids, compounds (1–3), together with seven known ones (4–10). Their structures were established by extensive spectroscopic methods and comparison of their data with those of the related known compounds. All the isolates possessed the 3β,5α,6β-trihydroxylated steroidal nucleus. The cytotoxicities against selected HL-60, HeLa and K562 tumor cell lines and anti-H1N1 (Influenza A virus (IAV)) activities for the isolates were evaluated. Compounds 2, 3 and 5–8 exhibited potent activities against K562 cell lines with IC₅₀ values ranging from 6.4 to 10.3 μM. Compounds 1, 6–8 potently inhibited the growth of HL-60 tumor cell lines, and 6 also showed cytotoxicity towards HeLa cell lines. In addition, preliminary structure-activity relationships for the isolates are discussed. The OAc group at C-11 is proposed to be an important pharmacophore for their cytotoxicities in the 3β,5α,6β-triol steroids. Compounds 4 and 9 exhibited significant anti-H1N1 IAV activity with IC₅₀ values of 19.6 and 36.7 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).     

New Trichothecenes Isolated from the Marine Algicolous Fungus Trichoderma brevicompactum

Eight trichothecenes, including four new compounds 1–4 and four known entities 5–8, together with one known cyclonerane (9) were isolated from the solid-state fermentation of Trichoderma brevicompactum NTU439 isolated from the marine alga Mastophora rosea. The structures of 1–9 were determined by 1D/2D NMR (nuclear magnetic resonance), MS (mass spectrometry), and IR (infrared spectroscopy) spectroscopic data. All of the compounds were evaluated for cytotoxic activity against HCT-116, PC-3, and SK-Hep-1 cancer cells by the SRB assay, and compound 8 showed promising cytotoxic activity against all three cancer cell lines with the IC₅₀ values of 3.3 ± 0.3, 5.3 ± 0.3, and 1.8 ± 0.8 μM, respectively. Compounds 1–2, 4–6, and 7–8 potently inhibited LPS-induced NO production, and compounds 5 and 8 showed markedly inhibited gelatinolysis of MMP-9 in S1 protein-stimulated THP-1 monocytes.     

Parathyrsoidins A–D,Four New Sesquiterpenoids from the Soft Coral Paralemnalia thyrsoides

Four new nardosinane-type sesquiterpenoids, parathyrsoidins A–D (1–4) were isolated from the soft coral Paralemnalia thyrsoides. The structures of parathyrsoidins A–D (1–4) were determined by extensive spectral analysis and their cytotoxicity against selected cancer cell lines as well as antiviral activity against human cytomegalovirus (HCMV) were evaluated in vitro.     

Three New Resveratrol Derivatives from the Mangrove Endophytic Fungus Alternaria sp.

Three new resveratrol derivatives, namely, resveratrodehydes A–C (1–3), were isolated from the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS, 1D and 2D NMR spectroscopic data. All compounds showed broad-spectrum inhibitory activities against three human cancer cell lines including human breast MDA-MB-435, human liver HepG2, and human colon HCT-116 by MTT assay (IC₅₀ < 50 μM). Among them, compounds 1 and 2 both exhibited marked cytotoxic activities against MDA-MB-435 and HCT-116 cell lines (IC₅₀ < 10 μM). Additionally, compounds 1 and 3 showed moderate antioxidant activity by DPPH radical scavenging assay.     

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.     

Two New Phenylhydrazone Derivatives from the Pearl River Estuary Sediment-Derived Streptomyces sp. SCSIO 40020

Two new phenylhydrazone derivatives and one new alkaloid, penzonemycins A–B (1–2) and demethylmycemycin A (3), together with three known compounds including an alkaloid (4) and two sesquiterpenoids (5–6), were isolated from the Streptomyces sp. SCSIO 40020 obtained from the Pearl River Estuary sediment. Their structures and absolute configurations were assigned by 1D/2D NMR, mass spectroscopy and X-ray crystallography. Compound 1 was evaluated in four human cancer cell lines by the SRB method and displayed weak cytotoxicity in three cancer cell lines, with IC₅₀ values that ranged from 30.44 to 61.92 µM, which were comparable to those of the positive control cisplatin. Bioinformatic analysis of the putative biosynthetic gene cluster indicated a Japp–Klingemann coupling reaction involved in the hydrazone formation of 1 and 2.     

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.     

New Andrastin-Type Meroterpenoids from the Marine-Derived Fungus Penicillium sp.

Three new andrastin-type meroterpenoids penimeroterpenoids A–C (1–3) together with two known analogs (4 and 5) were isolated from the cultures of the marine-derived Penicillium species (sp.). The structures of the new compounds were elucidated on the basis of 1- and 2-dimensional (1D/2D) Nuclear Magnetic Resonance (NMR) spectroscopic and mass spectrometric analysis. The absolute configurations of 1–3 were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compound 1 showed moderate cytotoxicity against A549, HCT116, and SW480 cell lines.     

Chevalones H–M: Six New α-Pyrone Meroterpenoids from the Gorgonian Coral-Derived Fungus Aspergillus hiratsukae SCSIO 7S2001

Six new α-pyrone meroterpenoid chevalones H–M (1–6), together with six known compounds (7–12), were isolated from the gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001 collected from Mischief Reef in the South China Sea. Their structures, including absolute configurations, were elucidated on the basis of spectroscopic analysis and X-ray diffraction data. Compounds 1–5 and 7 showed different degrees of antibacterial activity with MIC values of 6.25–100 μg/mL. Compound 8 exhibited potent cytotoxicity against SF-268, MCF-7, and A549 cell lines with IC₅₀ values of 12.75, 9.29, and 20.11 μM, respectively.     

Dichotocejpins A–C: New Diketopiperazines from a Deep-Sea-Derived Fungus Dichotomomyces cejpii FS110

Three new diketopiperazines, dichotocejpins A–C (1–3), together with eight known analogues (4–11), were isolated from the culture of the deep-sea sediment derived fungus Dichotomomyces cejpii FS110. Their structures, including absolute configurations, were elucidated by a combination of HRESIMS, NMR, X-ray crystallography, and ECD calculations. Compounds 4–6, 10–11 showed significant cytotoxic activities against MCF-7, NCI-H460, HepG-2, and SF-268 tumor cell lines. Compound 1 exhibited excellent inhibitory activity against α-glucosidase with an IC₅₀ of 138 μM.     

New Cytotoxic Cytochalasans from a Plant-Associated Fungus Chaetomium globosum kz-19

Four new cytochalasans, phychaetoglobins A–D (1–4), together with twelve known cytochalasans (5–16), were isolated from a mangrove-associated fungus Chaetomium globosum kz-19. The new structures were elucidated on the basis of extensive 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculations. The absolute configuration of 2 was established by application of Mosher’s method. Compounds 4–8 exhibited moderate cytotoxicities against A549 and HeLa cell lines with the IC₅₀ values less than 20 μM.     

Briarane Diterpenes from the South China Sea Gorgonian Coral,Junceella gemmacea

Four new briarane diterpenoids, junceellolides M–P (1–4), were isolated together with seven known analogs (5–11) from the South China Sea gorgonian, Junceella gemmacea. The structures of these compounds were elucidated by detailed spectroscopic analysis and comparison with the reported data. The absolute configuration of compounds 1–3 were determined based on an ECD experiment, while the absolute configuration of compound 4 was genetically determined. All the compounds were isolated for the first time from J. gemmacea. These compounds showed no growth inhibitory activity against A549, MG63 and SMMC-7721 cell lines in an in vitro bioassay.     

New Tripeptide Derivatives Asperripeptides A–C from Vietnamese Mangrove-Derived Fungus Aspergillus terreus LM.5.2

Three new tripeptide derivatives asterripeptides A–C (1–3) were isolated from Vietnamese mangrove-derived fungus Aspergillus terreus LM.5.2. Structures of isolated compounds were determined by a combination of NMR and ESIMS techniques. The absolute configurations of all stereocenters were determined using the Murfey’s method. The isolated compounds 1–3 contain a rare fungi cinnamic acid residue. The cytotoxicity of isolated compounds against several cancer cell lines and inhibition ability of sortase A from Staphylococcus aureus of asterripeptides A–C were investigated.     

Spirobisnaphthalenes from the Mangrove-Derived Fungus Rhytidhysteron sp. AS21B

Three new spirobisnaphthalenes (1–3) were isolated from the mangrove-derived fungus Rhytidhysteron sp., together with five known derivatives (4–8). The structures of the compounds were established on the basis of extensive spectroscopic data, and the relative configurations of their stereogenic carbons were determined by a single-crystal X-ray crystallographic analysis. Compounds 3–5 displayed cytotoxicity against both cancer cell lines, MCF-7 and CaSki, while 2 was active only on CaSKi cells.     

In Vitro Anticancer and Cancer-Preventive Activity of New Triterpene Glycosides from the Far Eastern Starfish Solaster pacificus

Sea stars or starfish (class Asteroidea) and holothurians or sea cucumbers (class Holothuroidea), belonging to the phylum Echinodermata (echinoderms), are characterized by different sets of glycosidic metabolites: the steroid type in starfish and the triterpene type in holothurians. However, herein we report the isolation of eight new triterpene glycosides, pacificusosides D–K (1–3, 5–9) along with the known cucumarioside D (4), from the alcoholic extract of the Far Eastern starfish Solaster pacificus. The isolated new compounds are closely related to the metabolites of sea cucumbers, and their structures of 1–3 and 5–9 were determined by extensive NMR and ESIMS techniques. Compounds 2, 5, and 8 have a new type of tetrasaccharide chain with a terminal non-methylated monosaccharide unit. Compounds 3, 6, and 9 contain another new type of tetrasaccharide chain, having 6-O-SO₃-Glc as one of the sugar units. The cytotoxic activity of 1–9 against non-cancerous mouse epidermal cells JB6 Cl41 and human melanoma cell lines SK-MEL-2, SK-MEL-28, and RPMI-7951 was determined by MTS assay. Compounds 1, 3, 4, 6, and 9 showed potent cytotoxicity against these cell lines, but the cancer selectivity (SI > 9) was observed only against the SK-MEL-2 cell line. Compounds 1, 3, 4, 6, and 9 at the non-toxic concentration of 0.1 μM significantly inhibited neoplastic cell transformation of JB6 Cl41 cells induced by chemical carcinogens (EGF, TPA) or ionizing radiation (X-rays and UVB). Moreover, compounds 1 and 4 at the non-toxic concentration of 0.1 µM possessed the highest inhibiting activity on colony formation among the investigated compounds and decreased the colonies number of SK-MEL-2 cells by 64% and 70%, respectively. Thus, triterpene glycosides 1 and 4 can be considered as prospective cancer-preventive and anticancer-compound leaders.     

Cytotoxic Polyketides from the Deep-Sea-Derived Fungus Engyodontium album DFFSCS021

Eight new chromones, engyodontiumones A–H (1–8), and three new phenol derivatives (9–11) together with eight known polyketides (12–19) were isolated from the deep-sea-derived fungus Engyodontium album DFFSCS021. Their structures were identified by extensive spectroscopic analysis. Compounds 8 and 16 showed significant selective cytotoxicity against human histiocytic lymphoma U937 cell line with IC₅₀ values of 4.9 and 8.8 μM, respectively. In addition, this is the first time to report that 8, 15 and 16 had mild antibacterial activity against Escherichia coli and Bacillus subtilis, and 15 showed potent antilarval activity against barnacle Balanus amphitrite larval settlement.