Litoamentenes A-K, eleven undescribed cembranoids with cytotoxicity from the South China Sea soft coral Litophyton amentaceum.

Eleven undescribed cembrane-type diterpenoids, named litoamentenes A-K (1-11), were isolated from the soft coral Litophyton amentaceum collected from the South China Sea. Their structures were elucidated by extensive analysis of spectroscopic data, comparison with the literature data, single crystal X-ray diffraction, quantum chemical calculations and TDDFT-ECD calculations. This is the first systematic investigation of L. amentaceum. In particular, compounds 1-3 are cembrane-type norditerpenoids that lack isopropyl side chains. Compound 6 is a cembrane-type norditerpenoid without a methyl group at C-4, the first natural product identified with this carbon skeleton. Compounds 6, 9 and 10 showed modest cytotoxicity against several human cancer cell lines with IC50 values ranging from 3.99 to 14.56 µM.

Lemneolemnanes A-D, Four Uncommon Sesquiterpenoids from the Soft Coral Lemnalia sp.

Four undescribed sesquiterpenoids, lemneolemnanes A-D (1-4), have been isolated from the marine soft coral Lemnalia sp. The absolute configurations of the stereogenic carbons of 1-4 were determined by single-crystal X-ray crystallographic analysis. Compounds 1 and 2 are epimers at C-3 and have an unusual skeleton with a formyl group on C-6. Compound 3 possesses an uncommonly rearranged carbon skeleton, while 4 has a 6/5/5 tricyclic system. Compound 1 showed significant anti-Alzheimer's disease (AD) activity in a humanized Caenorhabditis elegans AD pathological model.

Sarcoeleganolides H-K, new anti-thrombotic cembranes from soft coral Sarcophyton elegans.

Chemical investigation of soft coral the Sarcophyton elegans collected from the South China Sea led to the identification of four new cembranes, namely sarcoeleganolides H-K (1-4). Their structures and absolute configurations were established by 1D and 2D NMR spectroscopy, quantum chemical calculations of NMR chemical shifts and electronic circular dichroism (ECD) data analysis. Moreover, compound 2 exhibited moderate anti-thrombotic activity in zebrafish.

Seven New Lobane Diterpenoids from the Soft Coral Lobophytum catalai.

Seven new lobane diterpenoids, namely, lobocatalens A-G (1-7), were isolated from the Xisha soft coral Lobophytum catalai. Their structures, including their absolute configurations, were elucidated via spectroscopic analysis, comparison with the literature data, QM-MNR, and TDDFT-ECD calculations. Among them, lobocatalen A (1) is a new lobane diterpenoid with an unusual ether linkage between C-14 and C-18. In addition, compound 7 showed moderate anti-inflammatory activity in the zebrafish models and cytotoxic activity against the K562 human cancer cell line.

Terpenoids from the Sponge Sarcotragus sp. Collected in the South China Sea.

Sarcotragusolides A-D (1-4), four new butenolide sesterterpenes featuring a rare methyl-transferred 6/6/6-tricyclic fused ring system with a butyrolactone moiety, and echinohalimane B (8), an unprecedented monocyclic diterpenoid featuring a 2,7-ring-opened halimane-type skeleton, were isolated from the sponge Sarcotragus sp. A γ-hydroxybutenolide sesterterpene derivative (5), a new scalarane sesterterpene (7), a new subersin-type diterpenoid (10), and two known terpenoids were also isolated and identified. The discovery of sarcotragusolides C and D (3 and 4) with an unprecedented inversion of configuration implied a distinct biosynthetic pathway. The structures of these compounds were elucidated based on their spectroscopic data, single-crystal X-ray diffraction, chemical derivatization, and quantum chemical calculations. Compounds 1a, 1b, and 2 presented modest cytotoxic activities against several human cancer cell lines.

Sarcoelegans A-H, eight undescribed cembranes with anti-inflammatory and anti-thrombotic activities from the South China Sea soft coral Sarcophyton elegans.

Chemical investigation of the South China Sea soft coral Sarcophyton elegans has led to the isolation of eight undescribed cembranes, namely sarcoelegans A-H. Their structures and absolute configurations were unambiguously established by extensive analyses of spectroscopic data, X-ray diffraction, QM-NMR, and TDDFT-ECD calculations. Sarcoelegan A is composed of the rare tricyclo [11.2.1.0] hexadecane carbon framework which is the third compound of this scaffold. Sarcoelegan B and sarcoelegan C possess an unusual seven-membered ether ring, and (±)-sarcoelegan D has a seven-membered ring with the rare peroxo bridge. In addition, sarcoelegan A, (±)-sarcoelegan D, sarcoelegan E, (+)-sarcoelegan F, and (+)-sarcoelegan H exhibited anti-inflammatory activity in zebrafish and sarcoelegan C exhibited anti-thrombotic activity in zebrafish.

Two new spongian diterpene derivatives from the aquaculture sponge Spongia officinalis Linnaeus, 1759.

2ß,3α,19-Triacetoxy-17-hydroxyspongia-13(16),14-diene (1), a novel acetoxy diterpenoid, and 18-nor-2,17-hydroxyspongia-1,4,13(16),14-quaien-3-one (2), belonging to the rare 18-nor-spongian carbon skeleton, together with six related known metabolites (3‒8), were isolated from the aquaculture Spongia officinalis Linnaeus, 1759. Their structures were elucidated by comprehensive spectroscopic analysis, quantum chemical calculation of NMR parameters, and electronic circular dichroism (ECD). Compounds 3, 4, and 5 exhibited moderate inhibition against STAT3/NF-κB, HIF-1, Wnt signalling pathways. Compounds 1, 3, and 5 showed cytotoxicity activities against K562 cell line with IC50 values of 7.3, 3.5, and 6.4 µM, respectively.

Structural Investigation of Aaptourinamine by a Novel Module-Assembly-Based Calculation.

Natural products have various and complicated structures, which is still a challenge for elucidating these compounds, especially for those lacking two-dimensional nuclear magnetic resonance (2D NMR) correlations mainly caused by high C/H ratios or proton-deficient and multiple heteroatoms through the conventional structural analytical methods. We reported a novel module-assembly calculation method named Dooerafa, which included constructing the meta-structures by a grafting method based on the crucial and the limited 2D NMR correlations, ring-contraction strategy based on mechanic force field and quantum chemical theory, and self-assemble calculation in Python programming for shaping up the structural candidates along with DFT-GIAO calculation. This new method, verified by a known alkaloid spiroreticulatine with the structure determined by X-ray diffraction, was performed for the structural elucidation of aaptourinamine isolated from marine sponge Aaptos suberitoides, showing us a brand new scaffold of imidazo [4,5,1-ij]pyrrolo [3,2-f]quinolin-7(8H)-one, which has a biosynthetic relationship with the bioactive and structurally unique aaptamine alkaloid.

Subergorgines A-E, five new suberosanone-purine hybrids from the South China Sea gorgonian Subergorgia suberosa.

Five new suberosanone-purine hybrids, namely subergorgines A-E (1-5), were isolated from the South China Sea gorgonian Subergorgia suberosa. Their structures were elucidated on the basis of extensive spectroscopic data and the absolute configurations were clarified by the theoretical ECD calculation. Compounds 1-5 were rare purine alkaloids merged with the same suberosanone moiety via different C (6)-N bridges. Cytotoxic activities of the isolates were tested. Compound 4 was found to be the most active against the HL-60 cancer cell line with an IC50 value of 14.3 µM. A plausible biosynthetic pathway for suberosanone-purine hybrids was also discussed.

Sarcoeleganolides C-G, Five New Cembranes from the South China Sea Soft Coral Sarcophyton elegans.

Five new cembranes, named sarcoeleganolides C-G (1-5), along with three known analogs (6-8) were isolated from soft coral Sarcophyton elegans collected from the Yagong Island, South China Sea. Their structures and absolute configurations were determined by extensive spectroscopic analysis, QM-NMR, and TDDFT-ECD calculations. In addition, compound 3 exhibited better anti-inflammation activity compared to the indomethacin as a positive control in zebrafish at 20 µM.

Neopetrosins A-D and Haliclorensin D, Indole-C-Mannopyranosides and a Diamine Alkaloid Isolated from the South China Sea Marine Sponge Neopetrosia chaliniformis.

Four new indole-C-mannopyranoside alkaloids, neopetrosins A-D (1-4), together with one new diamine alkaloid, haliclorensin D (6), were isolated from the marine sponge Neopetrosia chaliniformis collected off Xisha Island in the South China Sea. Their structures and absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction, calculated electronic circular dichroism (ECD), and DP4+ probability analyses. Compounds 1, 2, and 4 exhibited in vivo hepatoprotective activity in a zebrafish model at a concentration of 20 µM.

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea.

Four new polyhydroxylated steroids lobophysterols E-H (1-4), together with three known compounds (5-7), were isolated from the soft coral Lobophytum pauciflorum collected at Xisha Island, China. The structures of the new compounds were elucidated by extensive spectroscopic analysis and comparison with NMR data of structurally related compounds reported in the literature. The absolute configuration of 1-3 was determined by X-ray diffraction. All the compounds have assessed the cytotoxicity against HL-60, K562, and Hela cells. Compound 1 showed weak cytotoxicity against K562 cells with an IC50 value of 19.03 µM. In addition, compound 1 also showed a moderate anti-inflammatory effect in zebrafish.

Identification of a Novel Inhibitor of TfR1 from Designed and Synthesized Muriceidine A Derivatives.

The transferrin receptor 1 (TfR1) plays a key role in cellular iron uptake through its interaction with iron-bound Tf. TfR1 is often reported to be overexpressed in malignant cells, and this increase may be associated with poor prognosis in different types of cancer, which makes it an attractive target for antitumor therapy. The marine natural product Muriceidine A is a potent anticancer agent reported in our previous work. In this study, we designed and synthesized a series of Muriceidine A derivatives and described the systematic investigation into their cytotoxic activities against four tumor cells. Most of the derivatives showed stronger antitumor activity and we found that the introduction of electron-donating groups at position C-2 of unsaturated piperidine was beneficial to anticancer activity and unsaturated piperidine was responsible for the antiproliferative activity. Among these compounds, 12b (methyl at position C-2 of unsaturated piperidine) exhibited the strongest cytotoxicity against MDA-MB-231 cells. Further pharmacological research showed that 12b bound to Transferrin receptor 1 (TfR1) directly caused iron deprivation and ROS imbalance along with the degradations of several oncoproteins, especially FGFR1, through the proteasome pathway; thus, inducing cell cycle arrest and apoptosis in MDA-MB-231 breast cancer cells. Our findings indicate that 12b is a promising lead compound targeting TfR1 for triple negative breast cancer.

Application of Principal Component Analysis (PCA) to the Evaluation and Screening of Multiactivity Fungi.

Continued innovation in screening methodologies remains important for the discovery of high-quality multiactive fungi, which have been of great significance to the development of new drugs. Mangrove-derived fungi, which are well recognized as prolific sources of natural products, are worth sustained attention and further study. In this study, 118 fungi, which mainly included Aspergillus spp. (34.62%) and Penicillium spp. (15.38%), were isolated from the mangrove ecosystem of the Maowei Sea, and 83.1% of the cultured fungi showed at least one bioactivity in four antibacterial and three antioxidant assays. To accurately evaluate the fungal bioactivities, the fungi with multiple bioactivities were successfully evaluated and screened by principal component analysis (PCA), and this analysis provided a dataset for comparing and selecting multibioactive fungi. Among the 118 mangrove-derived fungi tested in this study, Aspergillus spp. showed the best comprehensive activity. Fungi such as A. clavatonanicus, A. flavipes and A. citrinoterreus, which exhibited high comprehensive bioactivity as determined by the PCA, have great potential in the exploitation of natural products and the development of new drugs. This study demonstrated the first use of PCA as a time-saving, scientific method with a strong ability to evaluate and screen multiactive fungi, which indicated that this method can affect the discovery and development of new drugs.

Secondary metabolites from marine sponges of the genus Agelas: a comprehensive update insight on structural diversity and bioactivity.

As one of the most common marine sponges in tropical and subtropical oceans, the sponges of the genus Agelas, have emerged as unique and yet under-investigated pools for discovery of natural products with fabulous molecular diversity and myriad interesting biological activities. The present review highlights the chemical structure and biological activity of 355 compounds that have been isolated and characterized from the members of Agelas sponges, over the period of about five decades (from 1971 to November 2021). For a better understanding, these numerous compounds are firstly classified and presented according to their carbon skeleton as well as their biosynthetic origins. Relevant summaries focusing on the source organism and the associated bioactivity of these compounds belonging to different chemical classes are also provided. This review highlights sponges of the genus Agelas as exciting source for discovery of intriguing natural compounds.

Guaiane sesquiterpenes from the gorgonian Echinogorgia flora collected in the South China Sea.

Echinoflorine (1), a new dimethylamino-substituted guaipyridine alkaloid with a novel γ-lactone-cyclohepta[c]pyridine fused skeleton, and three new guaiane sesquiterpene lactones, echinofloranolides A-C (2-4), together with eight known guaiane sesquiterpenes were isolated from the gorgonian Echinogorgia flora collected in the South China Sea. Their structures were elucidated by 1D and 2D NMR, HRESIMS, calculated ECD and DP4+ probability analyses.

Dolabellane Diterpenes and Elemane Alkaloids from the Soft Coral Clavularia inflata Collected in the South China Sea.

Five new dolabellane diterpenes, clavularinlides A-E (1-5), and four new racemic elemane alkaloids, clavulacylides A-D (7-10), together with one known compound (6), were isolated from the soft coral Clavularia inflata collected in the South China Sea. Their structures were elucidated by 1D and 2D NMR, HRESIMS, calculated ECD, and DP4+ probability analyses. Compounds 1-7 showed anti-inflammatory activity in the zebrafish assay.

Lemnalemnanes A-C, Three Rare Rearranged Sesquiterpenoids from the Soft Corals Paralemnalia thyrsoides and Lemnalia sp.

Three novel sesquiterpenoids, lemnalemnanes A-C (1-3), were obtained from marine soft corals Paralemnalia thyrsoides and Lemnalia sp. Their structures were determined by 1D/2D NMR spectroscopy, HRESIMS, single-crystal X-ray diffraction analysis (Cu Kα), Mosher's method, and ECD quantum chemistry calculations. Lemnalemnane A (1) possessed an intriguing basket-like structure with a spiro[bicyclo[3.3.1]nonane-furan core, while lemnalemnanes B (2) and C (3) exhibited unusual 6/6/5 and 6/5/5 carbon skeletons, respectively. In the proposed biosynthesis pathway, 1-3 were suspected to originate from the same precursor, 4-O-deacetylparalemnolin D (4), a compound coisolated from both aforementioned species. Furthermore, lemnalemnane C (3) exhibited strong in vivo promoting-angiogenesis activity.

Jellynolide A, pokepola esters, and sponalisolides from the aquaculture sponge Spongia officinalis L.

Jellynolide A, an unreported bicyclic diterpenoid with an unprecedented penta-substituted carbon skeleton which implied an irregular biogenic pathway, together with four pairs of rare phosphate triesters, (±)-pokepola ester B-E, one undescribed related racemic furanoterpenoid, (±)-sponalisolide C, one undescribed furanoterpenoid, (-)-sponalisolide D, and two known (±)-sponalisolide B and dendrolasin carboxylic acid were isolated from the aquaculture Spongia officinalis L. Their structures were elucidated by comprehensive spectroscopic analysis, quantum chemical calculation of NMR parameters, and electronic circular dichroism (ECD). The plausible biosynthetic pathway of jellynolide A was proposed. (±)-Pokepola ester C exhibited significant inhibition against Wnt, HIF1 signaling pathways. (+)-Pokepola ester B and (-)-pokepola ester D showed moderate cytotoxicity activities.

Penitol A and Penicitols E-I: Citrinin Derivatives from Penicillium citrinum and the Structure Revision of Previously Proposed Analogues.

Penitol A (1), a new citrinin derivative with a rare tricyclic spiro skeleton, was isolated from a coral-derived strain of the fungus Penicillium citrinum. In addition, penicitols E-I (2-6), five new citrinin analogues, were coisolated. Their structures were determined by an analysis of 1D/2D NMR and HRESIMS data, statistical DP4+ analyses based on DFT-GIAO NMR calculations, quantum chemistry ECD calculations, and a single-crystal X-ray diffraction study. The structures of penicitol A (7) and two related synthetic intermediates were revised. Biological evaluation results revealed that penitol A (1) exhibited cytotoxic activity against K562 tumor cells, with an IC50 value of 8.8 µM. A proposed route of formation of compounds 1-7 was reported.