Polyketides from the mangrove-derived fungus Penicillium robsamsonii HNNU0006.

Seven polyketides, including an undescribed depsidone (1) and six previously reported 3,6,8-trihydroxy-1-methylxanthone (2), 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (3), methyl3-chloro-6-hydroxy-2-(4-hy-droxy-2-methoxy-6-methylphenoxy)-4- methoxybenzoate (4), xylarianin A (5), 4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydro-xymethyl-2-cyclohexen-1-one (6) and alternariol (7), have been isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. The structure of compound 1 was elucidated by extensive spectroscopic analysis and X-ray crystallography. Furthermore, all the compounds were evaluated their cytotoxic activities, and compounds 1 and 7 showed weak cytotoxicity against two cell lines Vero and A549 with IC50 values ranging from 95.6 and 296.5 µM, relative to the positive control Etoposide phosphate with IC50 values of 24.5 and 18.7 µM, respectively.

Anti-neuroinflammatory andrastin-type meroterpenoids from the marine-derived fungus Penicillium chrysogenum HNNU w0032.

A new andrastin-type meroterpenoid penimerodione A (1), and three known analogues (2-4), were isolated from the culture of a marine-derived fungus Penicillium chrysogenum HNNU w0032 by the guidance of MS/MS-based molecular networking. The planar structure of 1 was established by extensive NMR spectroscopic and HRESIMS analyses, and the absolute configuration was elucidated by a single-crystal X-ray diffraction. Compound 1 showed significant inhibitory effect on NO production in LPS-stimulated BV-2 macrophages with an IC50 value of 5.9 ± 0.3 µM. The Western blot result revealed that compound 1 exerted an anti-neuroinflammatory effect via the MAPK signalling pathway.

Structurally diverse isoquinoline alkaloids from the barks of Alangium salviifolium (L. f.) Wangerin and their cytotoxicity.

Eleven undescribed isoquinoline alkaloids (1-8, 14, 15, and 24), along with 19 analogues (9-13, 16-23, and 25-30) were isolated from the barks of Alangium salviifolium. The structures of the undescribed compounds were elucidated through the analysis of their HR-ESI-MS, 1D and 2D NMR, IR, UV, and X-ray diffraction. The absolute configuration of 8 was established via the ECD calculation. Notably, compounds 1/2 and 3/4 were two pairs of C-14 epimers. The isolated alkaloids were evaluated for their cytotoxicity against various cancer cell lines, including SGC-7901, HeLa, K562, A549, BEL-7402, HepG2, and B16, ß-carboline-benzoquinolizidine (14-22) and cepheline-type (24-28) alkaloids exhibited remarkable cytotoxicity, with IC50 values ranging from 0.01 to 48.12 µM. Remarkably, compounds 17 and 21 demonstrated greater cytotoxicity than the positive control doxorubicin hydrochloride. Furthermore, a significant proportion of these bioactive alkaloids possess a C-1' epimer configuration. The exploration of their structure-activity relationship holds promise for directing future investigations into alkaloids derived from Alangium, potentially leading to novel insights and therapeutic advancements.

Trilobolide-6-O-isobutyrate exerts anti-tumor effects on cholangiocarcinoma cells through inhibiting JAK/STAT3 signaling pathway.

Trilobolide-6-O-isobutyrate exhibits significant antitumor effects on cholangiocarcinoma (CCA) cells by effectively inhibiting the JAK/STAT3 signaling pathway. This study aims to investigate the mechanisms underlying the antitumor properties of trilobolide-6-O-isobutyrate, and to explore its potential as a therapeutic agent for CCA. This study illustrates that trilobolide-6-O-isobutyrate efficiently suppresses CCA cell proliferation in a dose- and time-dependent manner. Furthermore, trilobolide-6-O-isobutyrate stimulates the production of reactive oxygen species, leading to oxidative stress and initiation of apoptosis via the activation of the mitochondrial pathway. Data from xenograft tumor assays in nude mice confirms that TBB inhibits tumor growth, and that there are no obvious toxic effects or side effects in vivo. Mechanistically, trilobolide-6-O-isobutyrate exerts antitumor effects by inhibiting STAT3 transcriptional activation, reducing PCNA and Bcl-2 expression, and increasing P21 expression. These findings emphasizes the potential of trilobolide-6-O-isobutyrate as a promising therapeutic candidate for the treatment of CCA.

Alkaloid-metabolites from the mangrove-derived fungus Penicillium robsamsonii HNNU0006.

Nine metabolites, including three undescribed alkaloids pyripyropenes VW (1-2), penicioxa A (4), two previously reported pyripyropene A (3), oxaline (5), three grisephenone-type xanthone derivatives (6-8), and a diphenyl ether derivative 4-chloro-7,4'-dihydroxy-5,2'-dimethoxy-2-methylformate-6'-methybenzophone (9), were isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. Their structures were determined by spectroscopic analysis, ECD calculations, together with DP4+ probability analysis. Furthermore, all the isolated compounds were tested for cytotoxicity and anti-phytopathogenic fungal activities. Compounds 6-8 showed moderate cytotoxicity against tumor cell lines A549, with IC50 values ranging from 5.68 ± 0.21 to 9.71 ± 0.34 µg/mL, respectively.

Drimane-type sesquiterpenoids and their anti-inflammatory evaluation from Pyrrhoderma noxium HNNU0524.

Chemical investigation of a culture broth from the marine-derived fungus Pyrrhoderma noxium HNNU0524 yielded two new compounds including a drimane-type sesquiterpenoid named pyrrnoxin A (1) and a benzoic acid derivative, pyrrnoxin B (5), together with three related known analogues (2-4). The chemical structures of 1 and 5 were determined by detailed analysis of spectroscopic data, single-crystal X-ray crystallography, quantum mechanics-based DP4+ and ECD calculations. Compounds 2 and 3 moderately inhibited NO production of lipopolysaccharide-induced microglia cells BV2 with IC50 values of 26.6 and 60.5 µM, respectively.

Zeylleucapenoids A-D, Highly Oxygenated Diterpenoids with Anti-Inflammatory Activity from Leucas zeylanica (L.) R. Br.

Four previously undescribed highly oxygenated diterpenoids (1-4), zeylleucapenoids A-D, characterized by halimane and labdane skeletons, were isolated from the aerial parts of Leucas zeylanica. Their structures were elucidated primarily via NMR experiments. The absolute configuration of 1 was established using theoretical ECD calculations and X-ray crystallographic analysis, whereas those for 2-4 were assigned using theoretical ORD calculations. Zeylleucapenoids A-D were tested for anti-inflammatory activity against nitric oxide (NO) production in RAW264.7 macrophages, of which only 4 showed significant efficacy with an IC50 value of 38.45 µM. Further, active compound 4 was also evaluated for the inhibition of the release of pro-inflammatory cytokines TNF-α and IL-6 and was found to have a dose-dependent inhibitory effect, while it showed nontoxic activity for zebrafish embryos. A subsequent Western blotting experiment revealed that 4 inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, molecular docking analysis indicated that the possible mechanism of action for 4 may be bind to targets via hydrogen and hydrophobic bond interactions.

Four New Polyhydroxy Cyclohexanes from the Stems of Fissistigma tientangense.

Four undescribed polyhydroxy cyclohexanes, fissoxhydrylenes A-D (1-4), together with two known biogenetically related polyhydroxy cyclohexanes (5 and 6) were isolated from the stems of Fissistigma tientangense Tsiang et P. T. Li. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR, UV and Optical rotations data. The absolute configuration of 1 was confirmed by X-ray crystallographic. The absolute configurations of 2-4 were confirmed by chemical reaction and optical rotations. Compound 4 represent the first example of a no substituent polyhydroxy cyclohexanes from natural products. All isolated compounds were evaluated for their anti-inflammatory activities against the lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells in vitro. Compounds 3 and 4 showed inhibitory activities with the IC50 values of 16.63±0.06 µM and 14.38±0.08 µM, respectively.

Guaiane-Type Sesquiterpenes from the Stems of Fissistigma oldhamii.

Two new guaiane-type sesquiterpenes dysodensiols J and L, one new natural product dysodensiol K together with four known biogenetically related guaiane-type sesquiterpenes were isolated from the stems of Fissistigma oldhamii. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR and Optical rotations data. Compound 1 contains an uncommon five-membered ether ring. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed inhibitory activity with an IC50 value of 6.8 µM. Compounds 5-7 exhibited moderate inhibitory activity with IC50 values of 23.8, 26.6, and 27.1 µM, respectively.

Flavonoidal alkaloids from the flowers of Chromolaena odorata (L.) R.M.King & H.Rob.

A pair of epimers of flavonoid alkaloids, with a pyrrolidone moiety, 2S,5''R-eupodoratin A (1), 2S,5''S-eupodoratin A (2), together with two known analogues, drahebephin A (3), drahebephin B (4), were isolated from the flowers of Chromolaena odorata (L.) R.M.King & H.Rob. Their structures were elucidated on the basis of HR-ESI-MS, 1D/2D NMR spectral analyses. The absolute configuration of compounds (1) and (2) was determined by its experimental and calculated electronic circular dichroism (ECD) spectra. All compounds were isolated from the Asteraceae family for the first time. The ABTS·+ scavenging activity of compound (4) reached 93.56% at a concentration of 0.5 mM, while the scavenging capacity of positive control Trolox was 55.94%. In addition, all compounds show moderate antimicrobial activity against Escherichia coli (ATCC, 337304), Staphylococcus aureus (ATCC, 337371) and Candida albicans (ATCC, 186382) with a MIC value of more than 50 µg/mL.

Analogues of natural products yaequinolones as potential inflammatory inhibitors: Design, synthesis and biological evaluation.

Inflammation is connected with a variety of diseases and there is still a need to develop more effective and safer anti-inflammatory drugs. Herein, we synthesized, resolved, and characterized eight enantiopure isomers of yaequinolone J1 (1), yaequinolone J2 (2), 4'-desmethoxyyaequinolone J1 (3), and 4'-desmethoxyyaequinolone J2 (4). The key synthetic steps were extended and 34 racemic analogues modified at the 4-aryl, the N-position, and the pyran ring were designed and synthesized. All the synthesized compounds were evaluated for their anti-inflammatory activities in RAW 264.7 cells of which 13 compounds showed significant inhibition of nitric oxide (NO) production at a concentration of 0.1 µM, which was more potent than that of indomethacin. Furthermore, compounds (-)-3, (-)-4, 5h, and 6g reduced the production of IL-6 in LPS-stimulated RAW 264.7 cells at a concentration of 50 nM. A preliminary SAR indicated that 3'-Br (5h), 4'-NO2 (6g) on 4-phenyl and 3-bromobenzyl (7f) on the N-position were the most effective substituents. This is the first report of the anti-inflammatory yaequinolone alkaloids and the present study provided evidence for exploiting this series of highly efficacious derivatives for new anti-inflammatory agents.

Anthraquinones with potential antiproliferative activities from the fruits of Morinda citrifolia.

The phytochemical investigation on the fruits of Morinda citrifolia led to the isolation and characterization of a new anthraquinone, moricitrifone (1), along with seven known anthraquinones (2-8). The chemical structure of 1 was elucidated by extensive spectral analyses. The known compounds (2-8) were identified by comparing their spectral data with those reported in the literature. The antiproliferative activities of all isolated anthraquinones (1-8) against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 were evaluated in vitro. Compounds 1-8 exhibited remarkable antiproliferative activities with IC50 values ranging from 0.26 ± 0.05 to 16.58 ± 0.18 µM, which were comparable to those of doxorubicin.

Hainanxylogranolides A-F: New Limonoids isolated from the seeds of Hainan mangrove plant Xylocarpus granatum.

Six new limonoids, named hainanxylogranolides A-F (1-6), together with nineteen known ones (7-25) were isolated from the seeds of a Hainan mangrove Xylocarpus granatum. The structures of the new compounds were established by extensive NMR spectroscopic data combined with the DFT and TDDFT calculated electronic circular dichroism spectra. Hainanxylogranolide A (1) is the aromatic B-ring limonoid containing a central pyridine ring and a C-17 substituted γ(21)-hydroxybutenolide moiety. Hainanxylogranolide B (2) belongs to the small group of mexicanolides containing a C3-O-C8 bridge, whereas hainanxylogranolides C and D (3 and 4) are mexicanolides comprising a C1-O-C8 bridge. Compounds 9 and 25 posed obvious inhibition effect on the tube formation of HUVECs. There are only about 25% tube-like structures were observed at the concentration of 40.0 µM of compound 25. The antiviral activities of the isolates against herpes simplex virus-1 (HSV-1) and severe fever with thrombocytopenia syndrome virus (SFTSV) were tested in vitro. Compound 23 exhibited moderate anti-SFTSV activity with the IC50 value of 29.58 ± 0.73 µM. This is the first report of anti-angiogenic effect and anti-SFTSV activity of limonoids from the genus Xylocarpus.

Three new long-chain polyenes from the mangrove-derived fungus Penicillium herquei JX4.

One new epimer pair of long-chain polyenes penicilqueis E (1) and F (2), and one new long-chain polyene pinophol G (3), along with one known compound (4), were obtained from EtOAc extract of the mangrove-derived fungus Penicillium herquei JX4. Their structures were elucidated by detailed analysis of comprehensive spectroscopic data. The inhibitory activities of all compounds against the nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro were evaluated.

Bisabolane-type sesquiterpenoids with potential anti-inflammatory and anti-HIV activities from the stems and leaves of Morinda citrifolia.

The phytochemical study on the stems and leaves of Morinda citrifolia L. resulted in the isolation of a new naturally occurring bisabolane-type sesquiterpenoid, morincitrinoid A (1), together with five known analogues (2-6). The chemical structure of 1 was elucidated by comprehensive spectral analyses. The known compounds 2-6 were identified by comparing their spectral data with those reported in the literature, which were isolated from M. citrifolia for the first time. In addition, the anti-inflammatory and anti-HIV activities of compounds 1-6 were evaluated in vitro. Compounds 1-6 displayed significant inhibitory activities on NO (nitric oxide) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells with IC50 values ranging from 0.98 ± 0.07 to 6.32 ± 0.11 µM, which was comparable to hydrocortisone. Meanwhile, compounds 1-6 showed remarkable anti-HIV-1 reverse transcriptase (RT) effects with the EC50 values ranging from 0.16 to 6.29 µM.

Chemical constituents from the stem of Ficus pumila.

A new biphenyl compound: 5-aldehyde-4'-hydroxy-2,2'-dimethoxybiphenyl (1), along with 11 known phenolic compounds (2-12) were isolated from the stem of Ficus pumila Linn. Their structures were established by spectroscopic methods, including MS, UV, IR, 1 D and 2 D NMR. Compounds 4 and 10 showed weakly cytotoxicity against MCF-7, with IC50 values of 32.5 and 37.3 µM, respectively.

[Chemical constituents with α-glucosidase inhibitory activities from seeds of Morinda citrifolia (Noni)].

The present study investigated the chemical constituents and inhibitory activities against α-glucosidase from the seeds of Morinda citrifolia(Noni) by the chromatographic technique and semi-preparative HPLC.Fifteen compounds were isolated from the ethyl acetate extract of the seeds, and their structures were identified on the basis of physiochemical characteristics and spectroscopic data as(9S,2E,4Z,7Z)-9-hydroxydeca-2,4,7-trienoic acid(1), azelaic acid(2), scopoletin(3), ursolic acid(4), quercetin(5), cyclo-(L-Leu-L-Ile)(6), cyclo-(L-Phe-L-Ile)(7), cyclo-(L-Phe-L-Val)(8), cyclo-(L-Leu-L-Val)(9), cyclo-(L-Phe-L-Leu)(10), caffeic acid(11), 3,4-dihydroxycinnamaldehyde(12), p-hydroxybenzoic acid(13), p-hydroxy-cinnamic acid(14), and p-hydroxyphenethyl alcohol(15).Among them, compound 1 was a new fatty acid and compounds 7-10 and 12 were isolated from Morinda plant in the Rubiaceae family for the first time.Compounds 1, 2 and 4-15 were isolated from the seeds of M.citrifolia(Noni) for the first time.All isolated compounds were evaluated for the inhibitory activities against α-glucosidase and compounds 3-5 showed potential inhibitory activity with IC_(50) values of 160, 133, and 120 µmol·L~(-1), respectively.

Callnudoids A-H: Highly modified labdane diterpenoids with anti-inflammation from the leaves of Callicarpa nudiflora.

Eight undescribed 3,4-seco-norlabdane diterpenoids, callnudoids A-H, as well as two known analogues were isolated from the leaves of Callicarpa nudiflora. The structures were elucidated using spectroscopic methods and were compared with published NMR spectroscopic data. The absolute configurations of callnudoids D and E were defined based on ECD data or single-crystal X-ray diffraction. Callnudoids A-C are the highly modified labdane diterpenoids featuring rearranged 3,4-seco-ring and the formation of an undescribed cyclohexene moiety via C2-C18 cyclization. They only contain 15 carbon atoms on the carbon skeleton. Callnudoid D represents the unusual 3,4-seco-15,16-norlabdane diterpenoid with C13-C17 cyclization, and a putative biosynthesis pathway for callnudoids A, B, D, and E was proposed. All compounds were evaluated for their anti-inflammatory activities by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) released in RAW264.7 cells; callnudoids A-E and H, and methylcallicarpate obviously inhibited pro-inflammatory cytokines TNF-α and IL-1ß in a dose-dependent manner.

Talaromarins A-F: Six New Isocoumarins from Mangrove-Derived Fungus Talaromyces flavus TGGP35.

Six new isocoumarin derivative talaromarins A-F (1-6), along with 17 known analogues (7-23), were isolated from the mangrove-derived fungus Talaromyces flavus (Eurotiales: Trichocomaceae) TGGP35. Their structures were identified by detailed IR, UV, 1D/2D NMR and HR-ESI-MS spectra. The absolute configurations of new compounds were determined by the modified Mosher's method and a comparison of their CD spectra with dihydroisocoumarins described in the literature. The antioxidant, antibacterial, anti-phytopathogenic and inhibitory activity against α-glucosidase of all the isolated compounds were tested. Compounds 6-11, 17-19 and 21-22 showed similar or better antioxidant activity than the IC50 values ranging from 0.009 to 0.27 mM, compared with the positive control trolox (IC50 = 0.29 mM). Compounds 10, 18, 21 and 23 exhibited strong inhibitory activities against α-glucosidase with IC50 values ranging from 0.10 to 0.62 mM, while the positive control acarbose had an IC50 value of 0.5 mM. All compounds showed no antibacterial or anti-phytopathogenic activity at the concentrations of 50 µg/mL and 1 mg/mL, respectively. These results indicated that isocoumarins will be useful to developing antioxidants and as diabetes control agents.

Design, Semisynthesis, Insecticidal and Antibacterial Activities of a Series of Marine-Derived Geodin Derivatives and Their Preliminary Structure-Activity Relationships.

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2-37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC50 value of 89 µM, comparable to the positive control azadirachtin (IC50 = 70 µM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15-4.93 µM. The preliminary structure-activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.