Rhodococcus spongiicola sp. nov. and Rhodococcus xishaensis sp. nov., from marine sponges.

Two novel Rhodococcus strains, LHW50502T and LHW51113T, were isolated from marine sponges obtained on Xisha Island, Hainan Province, PR China. Rods and cocci, typical characteristics of the genus Rhodococcus, were observed. The strains contained meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall hydrolysates and galactose, arabinose, ribose and glucose as the whole-cell sugars. The major fatty acid identified was C16 : 0. MK-8(H4) was the predominat menaquinone of both strains. Stains LHW50502T and LHW51113T had almost identical (99.6 %) 16S rRNA gene sequences but shared relatively low similarities with previously characterized Rhodococcus species (well below 98.7 %). The results of phylogenetic analysis supported their closest relationship; however, the average nucleotide identity and digital DNA-DNA hybridization values between these two strains indicated that they belonged to distinct species. Taken together, the results of this study indicate that strains LHW50502T and LHW51113T represent two novel species of the genus Rhodococcus, for which the names Rhodococcus spongiicola sp. nov. (type strain LHW50502T=DSM 106291T=CCTCC AA 2018033T) and Rhodococcus xishaensis sp. nov. (type strain LHW51113T=DSM 106204T=CCTCC AA 2018034T) are proposed.

Aromatic Ring Substituted Aaptamine Analogues as Potential Cytotoxic Agents against Extranodal Natural Killer/T-Cell Lymphoma.

A chemical modification study was conducted on the marine natural product aaptamine (1), isolated from the marine sponge Aaptos aaptos. Thirty new derivatives substituted by various aromatic rings at the 3- and 7-positions of aaptamine were prepared by bromination, followed by the Suzuki coupling reaction. Sixteen compounds displayed cytotoxicities to four cancer cell lines (IC50 < 10 µM). In particular, compound 5i demonstrated a significant antiproliferative effect on the extranodal natural killer/T-cell lymphoma (ENKT) cell line SNK-6 with an IC50 value of 0.6 µM. Additionally, compound 5i showed cytotoxicities to multiple lymphoma cell lines, including Ramos, Raji, WSU-DLCL2, and SU-DHL-4 cells.

Pancreatic Lipase Inhibitory Cyclohexapeptides from the Marine Sponge-Derived Fungus Aspergillus sp. 151304.

Three new cyclohexapeptides, petrosamides A-C (1-3), were isolated from the sponge-derived fungus Aspergillus sp. 151304. Their structures were elucidated by detailed 1D and 2D spectroscopic analyses, and the absolute configurations of the amino acid residues were determined by the advanced Marfey's method. These peptides displayed significant and dose-dependent pancreatic lipase (PL) inhibitory activities, with IC50 values of 7.6 ± 1.5, 1.8 ± 0.3, and 0.5 ± 0.1 µM, respectively. Further inhibition kinetics analyses showed that compound 3 inhibited PL in a noncompetitive manner, while molecular dynamics simulation revealed that it could bind to PL at the entrance of the catalytic pocket.

Aaptolines A and B, Two New Quinoline Alkaloids from the Marine Sponge Aaptos aaptos.

Two new quinoline alkaloids, aaptolines A and B, were isolated from the marine sponge Aaptos aaptos. Their structures were determined by HR-ESI-MS data, NMR analysis, and X-ray crystallography. Structurally, aaptoline A is characterized as having a quinoline skeleton fused with a 1,4-dioxane motif at the C(7)-C(8) position, whereas aaptoline B possessed an intriguing 1H-pyrrolo[2,3-g]quinoline moiety. The cytotoxic assay of these compounds showed no cytotoxicity towards HepG2, A549, and PC9 cancer cell lines and had IC50 values greater than 20 µm.

Geodermatophilus marinus sp. nov., isolated from the marine sponge Leucetta chagosensis.

A novel actinobacterium, designated LHW52908T, was isolated from a marine sponge, Leucettachagosensis, collected in the South China Sea. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain LHW52908T was member of the family Geodermatophilaceae, with highest similarities to Geodermatophilus obscurus DSM 43160T (97.7 %), Geodermatophilus siccatus CF6T (97.6 %) and Geodermatophiluschilensis B12T (97.5 %). Multilocus sequence analysis confirmed that the strain should be a member of genus Geodermatophilus. Chemotaxonomic characteristics confirmed the genus-level affiliation of strain LHW52908T. Based on phylogenetic data, average nucleotide identity and digital DNA-DNA hybridization results, strain LHW52908T could be distinguished from its closest neighbours, representing a novel species of the genus Geodermatophilus, for which the name Geodermatophilusmarinus sp. nov. is proposed, with the type strain LHW52908T (=DSM 106570T=CCTCC AA 2018014T).

(-)-Calcaridine B, a new chiral aminoimidazole-containing alkaloid from the marine sponge Leucetta chagosensis.

LC-DAD/MS-based dereplication of organic extract of a calcareous sponge Leucetta chagosensis afforded one new chiral aminoimidazole-containing alkaloid, (-)-calcaridine B (1), along with one achiral imidazole analog leucettamine E (2) as well as one known imidazole derivative (2E, 9E)-pyronaamidine-9-(N-methylimine) (3). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparing with the literature. The cytotoxic activities of all isolates were evaluated against three human cancer cell lines, and compounds 1 and 3 exhibited mild cytotoxicities toward the MCF-7 cell line with IC50 values of 25.3-24.2 µM, respectively.

Imidazole Alkaloids and Their Zinc Complexes from the Calcareous Marine Sponge Leucetta chagosensis.

Five new imidazole derivatives (1-5), together with eight related known alkaloids, were isolated from a calcareous marine sponge, Leucetta chagosensis, collected from the South China Sea. Their structures were fully characterized by spectroscopic methods. Structurally, 1 possesses an unusual skeleton featuring imidazole and oxazolone rings linked via a nitrogen atom, whereas 2 bears an intriguing guanylurea-substituted imidazole ring. Compounds 4 and 5 were identified as zinc complexes; they represent the metal complex analogues of naamidine J (6) and pyronaamidine (7), respectively. Among the isolated compounds, 2 and 5 showed significant inhibitory activities toward the LPS-induced production of IL-6 in the human acute monocytic leukemia cell line THP-1, and 7 displayed cytotoxicity against MCF-7, PC9, A549, and breast cancer stem cells (MCF-7-Oct4-GFP) with IC50 values of 5.2, 5.6, 7.8, and 10 µM, respectively.

Leucanone A and naamine J, glycerol ether lipid and imidazole alkaloid from the marine sponge Leucandra sp.

Chemical investigation on CH2Cl2 extract of the marine sponge Leucandra sp. afforded two new compounds named leucanone A (1) and naamine J (2), together with eight known compounds (3-10). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparing with the literature. The cytotoxic activities of the compounds were evaluated against four cancer cell lines, and compound 2 showed mild cytotoxic activities against MCF-7, A549, HeLa, and PC9 cancer cell lines with IC50 values in the range of 20.1-45.3 µM.

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.

New Metabolites from the South China Sea Sponge Diacarnus megaspinorhabdosa.

Chemical investigation on CH2Cl2 extract of the marine sponge Diacarnus megaspinorhabdosa resulted in the isolation of two new farnesylacetone derivatives 1-2, a new γ-lactone 3, a known dinorditerpenone 4 and four known norsesterterpene peroxides 5-8. Their structures were elucidated by using one and two dimensional (1D and 2D)-NMR, high resolution-electrospray ionization (HR-ESI)-MS, and comparison with the literature. Compounds 1 and 2 were cis/trans-olefinic isomers and determined through nuclear Overhauser effect spectroscopy (NOESY) experiment. The absolute configuration of 3 was established by comparison of circular dichroism (CD) data with known lactones. The cytotoxic activities of the compounds were evaluated against five cancer cell lines, and compound 3 showed moderate cytotoxicity activities against cancer cell lines HeLa, H446, NCI-H460, SGC-7901 and MCF-7, with IC50 values in the range of 18.5 to 47.1 µM.

Two new 5,6-epoxysterols from calcareous marine sponge Leucetta chagosensis.

Chemical investigation on CH2Cl2 extract of the marine sponge Leucetta chagosensis, collected from the South China Sea, afforded two new 5,6-epoxysterols, 5α,6α-epoxycholesta-8(14),22(E)-diene-3ß,7α-diol (1) and (24R)-24-ethyl-5α,6α-epoxycholesta-8(14),22(E)-diene-3ß,7α-diol (2) along with ten known related steroid analogs (3-12). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparison with the literature. All isolates were tested for cytotoxicity against three tumor cell lines only known compounds 11 and 12 exhibited notable cytotoxic activity against A549 (IC50: 3.0 and 5.6 µM), PC9 (2.0 and 15.6 µM), and MCF-7 (9.4 and 11.8 µM) cell lines, respectively.

Gypensapogenin H, a novel dammarane-type triterpene induces cell cycle arrest and apoptosis on prostate cancer cells.

Gypensapogenin H (GH) is a novel dammarane-type triterpenes obtained from hydrolyzate of total saponins from Gynostemma pentaphyllum and its anti-tumor activity has been studied in previous work. In this study, we report the effects of this compound on human prostate cancer cells (DU145 and 22RV-1). It significantly inhibited proliferation, decreased survival, led to G1 cell cycle arrest and induced apoptosis in both cell lines, while having lesser effect on the growth of normal human gastric mucosa cells (GES-1), embryonic kidney cells (HEK293) and lung fibroblast cells (MRC5). Consistent with these phenotypes, we observed decreased expression of the cell cycle-related proteins cyclinD1, and CDK4, and increased expression of p21 in GH-treated cells. Besides, the anti-apoptotic Bcl-2 protein decreased in a dose-dependent manner, while Bax, cleaved caspase-3 and -9 increased upon GH treatment. Taken together, these results indicated GH exerted promising anticancer activity, and may represent a potential agent for the treatment of prostate cancer.