Labdane-Type Diterpenoids from Streptomyces griseorubens and Their Antimicrobial and Cytotoxic Activities.

Chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces griseorubens, resulted in the discovery of five new labdane-type diterpenoids: chlorolabdans A-C (1-3), epoxylabdans A and B (4 and 5), along with one known analog (6). The structures of the new compounds were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and by comparing their experimental data with those in the literature. The new compounds were evaluated for their antimicrobial activity, and 2 displayed significant activity against Gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging from 4 to 8 µg/mL. Additionally, 1, 2, and 4 were tested for their cytotoxicity against seven blood cancer cell lines by CellTiter-Glo (CTG) assay and six solid cancer cell lines by sulforhodamine B (SRB) assay; 1, 2, and 4 exhibited cytotoxic activities against some blood cancer cell lines, with concentration causing 50% cell growth inhibition (IC50) values ranging from 1.2 to 22.5 µM.

Meirols A-C: Bioactive Catecholic Compounds from the Marine-Derived Fungus Meira sp. 1210CH-42.

Three new catecholic compounds, named meirols A-C (2-4), and one known analog, argovin (1), were isolated from the marine-derived fungus Meira sp. 1210CH-42. Their structures were determined by extensive analysis of 1D, 2D NMR, and HR-ESIMS spectroscopic data. Their absolute configurations were elucidated based on ECD calculations. All the compounds exhibited strong antioxidant capabilities with EC50 values ranging from 6.01 to 7.47 µM (ascorbic acid, EC50 = 7.81 µM), as demonstrated by DPPH radical scavenging activity assays. In the α-glucosidase inhibition assay, 1 and 2 showed potent in vitro inhibitory activity with IC50 values of 184.50 and 199.70 µM, respectively (acarbose, IC50 = 301.93 µM). Although none of the isolated compounds exhibited cytotoxicity against one normal and six solid cancer cell lines, 1 exhibited moderate cytotoxicity against the NALM6 and RPMI-8402 blood cancer cell lines with GI50 values of 9.48 and 21.00 µM, respectively. Compound 2 also demonstrated weak cytotoxicity against the NALM6 blood cancer cell line with a GI50 value of 29.40 µM.

Streptinone, a New Indanone Derivative from a Marine-Derived Streptomyces massiliensis, Inhibits Particulate Matter-Induced Inflammation.

Inflammatory diseases caused by air pollution, especially from particulate matter (PM) exposure, have increased daily. Accordingly, attention to treatment or prevention for these inflammatory diseases has grown. Natural products have been recognized as promising sources of cures and prevention for not only inflammatory but also diverse illnesses. As part of our ongoing study to discover bioactive compounds from marine microorganisms, we isolated streptinone, a new indanone derivative (1), along with three known diketopiperazines (2-4) and piericidin A (5), from a marine sediment-derived Streptomyces massiliensis by chromatographic methods. The structure of 1 was elucidated based on the spectroscopic data analysis. The relative and absolute configurations of 1 were determined by 1H-1H coupling constants, 1D NOESY, and ECD calculation. The anti-inflammatory activities of 1 were evaluated through enzyme-linked immunosorbent assay (ELISA), Western blot, and qPCR. Compound 1 suppressed the production of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, by inhibiting the Toll-like receptor (TLR)-mediated nuclear factor kappa B (NF-κB) signaling pathway. Therefore, compound 1 could potentially be used as an agent in the prevention and treatment of diverse inflammatory disorders caused by particulate matter.

Rifamycin-Related Polyketides from a Marine-Derived Bacterium Salinispora arenicola and Their Cytotoxic Activity.

Eight rifamycin-related polyketides were isolated from the culture broth of a marine-derived bacterium Salinispora arenicola, including five known (2-5 and 8) and three new derivatives (1, 6, and 7). The structures of the new compounds were determined by means of spectroscopic methods (HRESIMS and 1D, 2D NMR) and a comparison of their experimental data with those previously reported in the literature. The isolated compounds were evaluated for their cytotoxicity against one normal, six solid, and seven blood cancer cell lines and 1 showed moderate activity against all the tested cell lines with GI50 values ranging from 2.36 to 9.96 µM.

Sesquiterpenes from Streptomyces qinglanensis and Their Cytotoxic Activity.

Nine sesquiterpenes, including eight pentalenenes (1-8) and one bolinane derivative (9), were isolated from the culture broth of a marine-derived actinobacterium Streptomyces qinglanensis 213DD-006. Among them, 1, 4, 7, and 9 were new compounds. Their planar structures were determined by spectroscopic methods (HRMS, 1D, and 2D NMR), and the absolute configuration was established by biosynthesis consideration and electronic-circular-dichroism (ECD) calculations. All the isolated compounds were screened for their cytotoxicity against six solid and seven blood cancer cell lines. Compounds 4-6 and 8 showed a moderate activity against all of the tested solid cell lines, with GI50 values ranging from 1.97 to 3.46 µM.

Thiolactones and Δ8,9-Pregnene Steroids from the Marine-Derived Fungus Meira sp. 1210CH-42 and Their α-Glucosidase Inhibitory Activity.

The fungal genus Meira was first reported in 2003 and has mostly been found on land. This is the first report of second metabolites from the marine-derived yeast-like fungus Meira sp. One new thiolactone (1), along with one revised thiolactone (2), two new Δ8,9-steroids (4, 5), and one known Δ8,9-steroid (3), were isolated from the Meira sp. 1210CH-42. Their structures were elucidated based on the comprehensive spectroscopic data analysis of 1D, 2D NMR, HR-ESIMS, ECD calculations, and the pyridine-induced deshielding effect. The structure of 5 was confirmed by oxidation of 4 to semisynthetic 5. In the α-glucosidase inhibition assay, compounds 2-4 showed potent in vitro inhibitory activity with IC50 values of 148.4, 279.7, and 86.0 µM, respectively. Compounds 2-4 exhibited superior activity as compared to acarbose (IC50 = 418.9 µM).

Pyrrole-Containing Alkaloids from a Marine-Derived Actinobacterium Streptomyces zhaozhouensis and Their Antimicrobial and Cytotoxic Activities.

Two new alkaloids, streptopyrroles B and C (1 and 2), were discovered through a chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces zhaozhouensis, along with four known analogs (3-6). The structures of the new compounds were elucidated by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and a comparison of their experimental data with literature values. The new compounds were evaluated for their antimicrobial activity by standard broth dilution assay, and the tested compounds showed significant activity against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 0.7 to 2.9 µM, and kanamycin was used as a positive control with MIC values ranging from <0.5 to 4.1 µM. Additionally, 1, 3, and 5 were evaluated for their cytotoxicity against six tumor cell lines by sulforhodamine B (SRB) assay, and these compounds displayed cytotoxic activities against all the tested cell lines, with concentration causing 50% cell growth inhibition (GI50) values ranging from 4.9 to 10.8 µM, while a positive control, adriamycin, showed GI50 values of 0.13-0.17 µM.

New Angucycline Glycosides from a Marine-Derived Bacterium Streptomyces ardesiacus.

Chemical investigation of the ethyl acetate extract from the culture broth of the marine-derived actinobacterium Streptomyces ardesiacus 156VN-095 led to the isolation of three hitherto undescribed angucycline glycosides, including urdamycins W and X (1 and 2) and grincamycin U (9), as well as their seven known congeners. The structures of the new compounds were elucidated by means of spectroscopic methods (HRESIMS, 1D and 2 D NMR) and comparison of their experimental data with literature values. Compounds 1-3 and 9 were evaluated for their anti-Gram-positive bacterial effect and cytotoxicity against six cancer cell lines. Compound 1 displayed significant cytotoxicity against all the tested cell lines with GI50 values of 0.019-0.104 µM. Collectively, these findings highlight the potential of angucycline glycosides as leading structures for the development of new anti-cancer drugs.

Aspersterols A-D, Ergostane-Type Sterols with an Unusual Unsaturated Side Chain from the Deep-Sea-Derived Fungus Aspergillus unguis.

Four previously undescribed ergostane-type sterols, aspersterols A-D (1-4), were isolated from a deep-sea-derived fungus, Aspergillus unguis IV17-109. The structures of the new compounds were determined by extensive analyses of their spectroscopic data, pyridine-induced deshielding effect, Mosher's method, and electronic circular dichroism calculations. The key feature of these sterols is the presence of a rare unsaturated side chain with conjugated double bonds at Δ17 and Δ22. The absolute configuration of C-24 in the side chain was determined by hydrogenation and comparing 13C NMR chemical shifts of the hydrogenated products with literature values. In addition, aspersterol A (1) is the second representative of anthrasteroids with a hydroxy group at the C-2 position. Compound 1 showed cytotoxicity against six cancer cell lines, with GI50 values of 3.4 ± 0.3 to 4.5 ± 0.7 µM, while 2-4 showed anti-inflammatory activity, with IC50 values ranging from 11.6 ± 1.6 to 19.5 ± 1.2 µM.

New Glycosylated Secondary Metabolites from Marine-Derived Bacteria.

Three new glycosylated secondary metabolites, including a new indole alkaloid, pityriacitrin D (1), and two new trehalose lipids (2 and 3), together with three known compounds (4-6) were isolated from two marine-derived bacterial strains, Bacillus siamensis 168CLC-66.1 and Tsukamurella pseudospumae IV19-045. The structures of 1-3 were determined by extensive analysis and comparison of their spectroscopic data with literature values. The absolute configurations of sugar moieties were determined by chemical derivatization followed by LC-MS analysis. Cytotoxicity of 1-3 against six cancer cell lines was evaluated by SRB assay, and 1 showed moderate activity against all the tested cell lines with GI50 values ranging from 8.0 to 10.9 µM.

Nitrogen-Containing Secondary Metabolites from a Deep-Sea Fungus Aspergillus unguis and Their Anti-Inflammatory Activity.

Aspergillus is well-known as the second-largest contributor of fungal natural products. Based on NMR guided isolation, three nitrogen-containing secondary metabolites, including two new compounds, variotin B (1) and coniosulfide E (2), together with a known compound, unguisin A (3), were isolated from the ethyl acetate (EtOAc) extract of the deep-sea fungus Aspergillus unguis IV17-109. The planar structures of 1 and 2 were elucidated by an extensive analysis of their spectroscopic data (HRESIMS, 1D and 2D NMR). The absolute configuration of 2 was determined by comparison of its optical rotation value with those of the synthesized analogs. Compound 2 is a rare, naturally occurring substance with an unusual cysteinol moiety. Furthermore, 1 showed moderate anti-inflammatory activity with an IC50 value of 20.0 µM. These results revealed that Aspergillus unguis could produce structurally diverse nitrogenous secondary metabolites, which can be used for further studies to find anti-inflammatory leads.

Antibacterial and Cytotoxic Phenolic Polyketides from Two Marine-Derived Fungal Strains of Aspergillus unguis.

A chemical investigation on the EtOAc extracts from two marine-derived fungal strains of Aspergillus unguis resulted in the isolation of three previously undescribed phenolic polyketides including unguidepside C (1), aspersidone B (3), and agonodepside C (12), and their 14 known congeners. The structures of the new compounds were determined based on detailed analysis and comparison of their spectroscopic data with literature values, as well as Snatzke's method. The new compounds (1, 3, and 12) displayed a significant anti-Gram-positive bacterial activity, with MIC values ranging from 5.3 to 22.1 µM. Additionally, the isolated compounds (1-11 and 13-16) were evaluated for their cytotoxicity against a panel of tumor cell lines. Most of them (except for 9) displayed cytotoxicity against all the tested cell lines, with IC50 values ranging from 2.5 to 46.9 µM.

Streptoglycerides E-H, Unsaturated Polyketides from the Marine-Derived Bacterium Streptomyces specialis and Their Anti-Inflammatory Activity.

Four new streptoglycerides E-H (1-4), with a rare 6/5/5/-membered ring system, were isolated from a marine-derived actinomycete Streptomyces specialis. The structures of 1-4 were elucidated by detailed analysis of HRESIMS, 1D and 2D NMR data and ECD spectra as well as comparison of their spectroscopic data with those reported in literature. Compounds 1-4 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production in Raw 264.7 cells with IC50 values ranging from 3.5 to 10.9 µM. Especially, 2 suppressed mRNA expression levels of iNOS and IL-6 without cytotoxicity.

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.

Reisolation and Structure Revision of Asperspiropene A.

Asperspiropene A was originally reported to have a unique 1,8-dioxaspiro[4.5]decane skeleton. During the course of our ongoing research for novel marine natural products, we isolated compound 1, which has identical 1D and 2D NMR data to asperspiropene A. Detailed and careful analysis of spectroscopic data led us to revise the structure of asperspiropene A and to determine its absolute configuration.