New Isomalabaricane-Derived Metabolites from a <i>Stelletta</i> sp. Marine Sponge

In continuation of our studies on a Vietnamese collection of a Stelletta sp., sponge we have isolated two new isomalabaricane triterpenoids, stellettins Q and R (1 and 2), and four new isomalabaricane-derived nor-terpenoids, stellettins S-V 3–6, along with previously known globostelletin N. Among them, compound 3 contains an acetylenic fragment, unprecedented in the isomalabaricane family and extremely rare in other marine sponge terpenoids. The structures and absolute configurations of all new compounds were established by extensive NMR, MS, and ECD analyses together with quantum-chemical modeling. Additionally, according to obtained new data we report the correction in stereochemistry of two asymmetric centers in the structures of two known isomalabaricanes, 15R,23S for globostelletin M and 15S,23R for globostelletin N

New Isomalabaricane-Derived Metabolites from a Stelletta sp. Marine Sponge

In continuation of our studies on a Vietnamese collection of a Stelletta sp., sponge we have isolated two new isomalabaricane triterpenoids, stellettins Q and R (1 and 2), and four new isomalabaricane-derived nor-terpenoids, stellettins S-V 3&ndash;6, along with previously known globostelletin N. Among them, compound 3 contains an acetylenic fragment, unprecedented in the isomalabaricane family and extremely rare in other marine sponge terpenoids. The structures and absolute configurations of all new compounds were established by extensive NMR, MS, and ECD analyses together with quantum-chemical modeling. Additionally, according to obtained new data we report the correction in stereochemistry of two asymmetric centers in the structures of two known isomalabaricanes, 15R,23S for globostelletin M and 15S,23R for globostelletin N

Polyphenolic Compounds from <i>Lespedeza bicolor</i> Protect Neuronal Cells from Oxidative Stress

Pterocarpans and related polyphenolics are known as promising neuroprotective agents. We used models of rotenone-, paraquat-, and 6-hydroxydopamine-induced neurotoxicity to study the neuroprotective activity of polyphenolic compounds from Lespedeza bicolor and their effects on mitochondrial membrane potential. We isolated 11 polyphenolic compounds: a novel coumestan lespebicoumestan A (10) and a novel stilbenoid 5’-isoprenylbicoloketon (11) as well as three previously known pterocarpans, two pterocarpens, one coumestan, one stilbenoid, and a dimeric flavonoid. Pterocarpans 3 and 6, stilbenoid 5, and dimeric flavonoid 8 significantly increased the percentage of living cells after treatment with paraquat (PQ), but only pterocarpan 6 slightly decreased the ROS level in PQ-treated cells. Pterocarpan 3 and stilbenoid 5 were shown to effectively increase mitochondrial membrane potential in PQ-treated cells. We showed that pterocarpans 2 and 3, containing a 3’-methyl-3’-isohexenylpyran ring; pterocarpens 4 and 9, with a double bond between C-6a and C-11a; and coumestan 10 significantly increased the percentage of living cells by decreasing ROS levels in 6-OHDA-treated cells, which is in accordance with their rather high activity in DPPH• and FRAP tests. Compounds 9 and 10 effectively increased the percentage of living cells after treatment with rotenone but did not significantly decrease ROS levels

Phanogracilins A–C, New Bibenzochromenones of Crinoid <i>Phanogenia gracilis</i> (Hartlaub, 1890)

Three new bibenzochromenones named phanogracilins A–C (1–3) were isolated from the crinoid Phanogenia gracilis. The structure of 1 was established using X-ray crystallography as 5,5′,6,6′,8,8′-hexahydroxy-2,2′-dipropyl-4H,4′H-[7,9′-bibenzo[g]chromene]-4,4′-dione. This allowed us to assign reliably 2D NMR signals for compound 1 and subsequently for its isomer 2 that differed in the connecting position of two benzochromenone moieties (7,10′ instead of 7,9′), and compound for 3 that differed in the length of the aliphatic chain of one of the fragments. Compound 4 was derived from 1 in alkaline conditions, and its structure was elucidated as 5,5′,6′,8,8′-pentahydroxy-2,2′-dipropyl-4H,4′H-[7,9′-bibenzo[g]chromene]-4,4′,6,9-tetraone. Even though compounds 1–4 did not contain stereo centers, they possessed notable optical activity due to sterical hindrances, which limited the internal rotation of two benzochromenone fragments around C(7)–C(9′/10′) bonds. Isolated bibenzochromenones 1–4 were tested for their antiradical, neuroprotective and antimicrobial activities. Compounds 1, 3 and 4 demonstrated significant antiradical properties towards ABTS radicals higher than the positive control trolox. Compounds 1 and 4 exhibited moderate neuroprotective activity, increasing the viability of rotenone-treated Neuro-2a cells at a concentration of 1 µM by 9.8% and 11.8%, respectively. Compounds 1 and 3 at concentrations from 25 to 100 μM dose-dependently inhibited the growth of Gram-positive bacteria S. aureus and yeast-like fungi C. albicans, and they also prevented the formation of their biofilms. Compounds 2 and 4 exhibited low antimicrobial activity

Piltunines A–F from the Marine-Derived Fungus Penicillium piltunense KMM 4668

Six new carotane sesquiterpenoids piltunines A&ndash;F (1&ndash;6) together with known compounds (7&ndash;9) were isolated from the marine-derived fungus Penicillium piltunense KMM 4668. Their structures were established using spectroscopic methods. The absolute configurations of 1&ndash;7 were determined based on circular dichroism (CD) and nuclear Overhauser spectroscopy (NOESY) data as well as biogenetic considerations. The cytotoxic activity of some of the isolated compounds and their effects on regulation of reactive oxygen species (ROS) and nitric oxide (NO) production in lipopolysaccharide-stimulated macrophages were examined

Zosteropenillines: Polyketides from the MarineDerived Fungus Penicillium thomii

Twelve new polyketides, zosteropenillines A–L (1–12), together with known polyketide pallidopenilline A (13), were isolated from the ethylacetate extract of the fungus Penicillium thomii associated with the seagrass Zostera marina. Their structures were established based on spectroscopic methods. The absolute configuration of zosteropenilline A (1) as 4R, 5S, 8S, 9R, 10R, and 13S was determined by a combination of the modified Mosher’s method, X‐ray analysis, and NOESY data. Absolute configurations of zosteropenillines B–D (2–4) were determined by timedependent density functional theory (TD‐DFT) calculations of ECD spectra. The effect of compounds 1–3, 7, 8, 10, and 11 on the viability of human drug‐resistant prostate cancer cells PC3 as well as on autophagy in these cancer cells and inhibitory effects of compounds 1, 2, and 8–10 on NO production in LPS‐induced RAW 264.7 murine macrophages were examined

New Guanidine Alkaloids Batzelladines O and P from the Marine Sponge <i>Monanchora pulchra</i> Induce Apoptosis and Autophagy in Prostate Cancer Cells

Two new guanidine alkaloids, batzelladines O (1) and P (2), were isolated from the deep-water marine sponge Monanchora pulchra. The structures of these metabolites were determined by NMR spectroscopy, mass spectrometry, and ECD. The isolated compounds exhibited cytotoxic activity in human prostate cancer cells PC3, PC3-DR, and 22Rv1 at low micromolar concentrations and inhibited colony formation and survival of the cancer cells. Batzelladines O (1) and P (2) induced apoptosis, which was detected by Western blotting as caspase-3 and PARP cleavage. Additionally, induction of pro-survival autophagy indicated as upregulation of LC3B-II and suppression of mTOR was observed in the treated cells. In line with this, the combination with autophagy inhibitor 3-methyladenine synergistically increased the cytotoxic activity of batzelladines O (1) and P (2). Both compounds were equally active in docetaxel-sensitive and docetaxel-resistant prostate cancer cells, despite exhibiting a slight p-glycoprotein substrate-like activity. In combination with docetaxel, an additive effect was observed. In conclusion, the isolated new guanidine alkaloids are promising drug candidates for the treatment of taxane-resistant prostate cancer

Anthraquinone Derivatives and Other Aromatic Compounds from Marine Fungus <i>Asteromyces cruciatus</i> KMM 4696 and Their Effects against <i>Staphylococcus aureus</i>

New anthraquinone derivatives acruciquinones A–C (1–3), together with ten known metabolites, were isolated from the obligate marine fungus Asteromyces cruciatus KMM 4696. Acruciquinone C is the first member of anthraquinone derivatives with a 6/6/5 backbone. The structures of isolated compounds were established based on NMR and MS data. The absolute stereoconfigurations of new acruciquinones A–C were determined using ECD and quantum chemical calculations (TDDFT approach). A plausible biosynthetic pathway of the novel acruciquinone C was proposed. Compounds 1–4 and 6–13 showed a significant antimicrobial effects against Staphylococcus aureus growth, and acruciquinone A (1), dendryol B (4), coniothyrinone B (7), and ω-hydroxypachybasin (9) reduced the activity of a key staphylococcal enzyme, sortase A. Moreover, the compounds, excluding 4, inhibited urease activity. We studied the effects of anthraquinones 1, 4, 7, and 9 and coniothyrinone D (6) in an in vitro model of skin infection when HaCaT keratinocytes were cocultivated with S. aureus. Anthraquinones significantly reduce the negative impact of S. aureus on the viability, migration, and proliferation of infected HaCaT keratinocytes, and acruciquinone A (1) revealed the most pronounced effect

Lissodendoric Acids A and B, Manzamine-Related Alkaloids from the Far Eastern Sponge Lissodendoryx florida

The first representatives of a new group of manzamine-related alkaloids with a previously unknown skeletal systems, namely, lissodendoric acids A (<b>1</b>) and B (<b>2</b>), were isolated from the sponge Lissodendoryx florida collected from the Sea of Okhotsk. The structures and absolute configurations have been elucidated by extensive spectroscopic analysis together with chemical transformations and quantum-chemical modeling. The lissodendoric acids show a potent capability to decrease the production of reactive oxygen species in neuroblastoma Neuro 2a and somewhat increase the survival of these cells upon treatment with 6-hydroxydopamine (an <i>in vitro</i> antiparkinson biotest)

Meroantarctines A–C, Meroterpenoids with Rearranged Skeletons from the Alga-Derived Fungus <i>Penicillium antarcticum</i> KMM 4685 with Potent p‑Glycoprotein Inhibitory Activity

New meroterpenoids, meroantarctines A–C (1–3), with unique 6/5/6/6, 6/5/6/5/6, and 6/5/6/5 polycyclic systems were isolated from the alga-derived fungus Penicillium antarcticum KMM 4685. Their structures were elucidated by spectroscopic methods, X-ray diffraction, and quantum chemical calculations. A biogenetic pathway for 1–3 was proposed. Meroantarctines A–C (1–3) inhibited p-glycoprotein activity and could resensitize drug-resistant cancer cells to docetaxel