Dayaolingzhiols A−E,AchE inhibitory meroterpenoids from Ganoderma lucidum

Ganoderma mushrooms are widely used as effective medicines for treating and preventing chronic diseases. In this study, five new meroterpenoids, dayaolingzhiols A (1) and B (2) featuring a 6/6/6 ring system, dayaolingzhiols C?E (3–5) harboring a γ-lactone motif, along with eight known ones (6–13), were purified from G. lucidum. To clarify their chemical structures, spectroscopic and ECD and OR computational methods were used. In addition, the inhibition of all the new meroterpenoids against AChE was evaluated, disclosing that (+)-4 and (±)-5 possess potent AChE inhibitory activities with respective IC₅₀ values of 8.52?±?1.90?μM and 7.37?±?0.52?μM.     

Marinocyanins,cytotoxic bromo-phenazinone meroterpenoids from a marine bacterium from the streptomycete clade MAR4

Six cytotoxic and antimicrobial metabolites of a new bromo-phenazinone class, the marinocyanins A-F (1–6), were isolated together with the known bacterial metabolites 2-bromo-1-hydroxyphenazine (7), lavanducyanin (8, WS-9659A) and its chlorinated analog WS-9659B (9). These metabolites were purified by bioassay-guided fractionation of the extracts of our MAR4 marine actinomycete strains CNS-284 and CNY-960. The structures of the new compounds were determined by detailed spectroscopic methods and marinocyanin A (1) was confirmed by crystallographic methods. The marinocyanins represent the first bromo-phenazinones with an N-isoprenoid substituent in the skeleton. Marinocyanins A-F show strong to weak cytotoxicity against HCT-116 human colon carcinoma and possess modest antimicrobial activities against Staphylococcus aureus and amphotericin-resistant Candida albicans.     

Hyperterpenoids A and B: Two pairs of unprecedented 6/6/4/6/6 polycyclic cyclobutane meroterpenoids with potent neuroprotective and anti-inflammatory activities from Hypericum beanii

Hyperterpenoid A (1) and B (2), two pairs of enantiomers, with an unprecedented 6/6/4/6/6 polycyclic skeleton, along with one known compoud hypermonone A (3) were isolated from Hypericum beanii. The racemate (±)-1 and (±)-2 were successfully separated into the two optically pure enantiomers (ee ≥ 99%) using a preparative HPLC system. Their absolute configurations were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction method. The related plausible biogenetic pathways were presented. Compound 1-3 showed significant neuroprotective activity and potential anti-inflammatory activity. The result that (+)-2 and (-)-2 presented different anti-inflammatory properties, may lead us to new discovery of structure activity relationship between racemates, enantiomers, and diastereomers, as well as further research regarding the binding of drugs to target proteins.     

Yojironins A−D, meroterpenoids and prenylated acylphloroglucinols from Hypericum yojiroanum

Two new meroterpenoids, yojironins A (1) and B (2), were isolated from the whole plants of Hypericum yojiroanum, together with two new prenylated acylphloroglucinols, yojironins C (3) and D (4). Their structures were elucidated by spectroscopic data. Yojironins A (1) and B (2) are biogenetically unique meroterpenoids, which seem to be composed of two acetate units with a 2-methylbutanoyl group and three isoprene units. Yojironin A (1) exhibited antimicrobial activity.     

COX-2 and JAK3 inhibitory meroterpenoids from the mushroom Ganoderma theaecolum

Ganoderma mushrooms possess antioxidant, anticancer, and immunomodulatory properties. In this study, eleven new meroterpenoids, ganotheaecolumols A-K (1–6, 10,11, 13, 14, and 17), together with nine known ones (7–9, 12, 15, 16, and 18–20) were isolated from the fruiting bodies of G. theaecolum. Their structures were elucidated by spectroscopic and computational methods. All the new compounds and iso-ganotheaecolumol I (12) were tested for their inhibitory activities against COX-2 and JAK3 kinases, and cytotoxic effects. It was found that most meroterpenoids could inhibit COX-2 and JAK3 with compounds 3, 4, 12, 13, and 17 having IC₅₀ values of 1.05?±?0.10, 1.38?±?0.11, 2.61?±?0.79, 3.47?±?0.58, and 4.84?±?0.60?μM towards COX-2. Whereas, none of the test compounds exhibited cytotoxic effects against human cancer cells (K562, A549, and Huh-7).     

Hyperinoids A and B,two polycyclic meroterpenoids from Hypericum patulum

Hyperinoids A (1) and B (2), two prenylated acylphloroglucinol related meroterpenoids, were isolated from Hypericum patulum. Compound 1 incorporates an unprecedented 11,12-dioxatetracyclo[5.4.3.0^1,7.0^4,14]tetradecane system, while 2 possesses a unique 10,11-dioxatetracyclo[5.3.3.0^1,7.0^4,13]tridecane system. Their structures were established by spectroscopic analysis and X-ray crystallographic data. Compounds 1 and 2 were identified as potent NF-κB inhibitors and suppressed the LPS-induced inflammatory responses in RAW 246.7 macrophages and primary mouse BMDM cells     

Psiguamers A–C,three cytotoxic meroterpenoids bearing a methylated benzoylphloroglucinol framework from Psidium guajava and total synthesis of 1 and 2

Three sesquiterpene-based meroterpenoids psiguamers A–C (1–3) with new skeletons were isolated from Psidium guajava leaves. Compounds (±)-1 and (±)-2 were two pairs of humulene-derived meroterpenoids bearing a rare methylated benzoylphloroglucinol unit, while 3 was an unprecedented adduct of bicyclogermacrene and methylated benzoylphloroglucinol. Their structures were determined based on comprehensive analyses of spectroscopic data, calculated electronic circular dichroism (ECD) spectra, total synthesis, and X-ray crystallographic data. The biomimetic synthesis of (±)-1 and (±)-2 was achieved. Compound (+)-1 exhibited cytotoxic activities against five human tumor cell lines (HCT-116, HepG2, BGC-823, A549, and U251), with IC₅₀ values of 2.94, 9.01, 6.45, 5.42, and 5.33 μmol/L, respectively.     

Bioactive meroterpenoids and alkaloids from the fungus Eurotium chevalieri

Five new meroterpenoids, chevalones A-D (1-4), aszonapyrone B (8), and a new sequiterpene alkaloid, eurochevalierine (5), together with four known compounds, sequiterpene (6), terpenoid pyrrolobenzoxazine named CJ-12662 (7), meroterpenoid, aszonapyrone A (9), and ergosterol were isolated from the fungus Eurotium chevalieri. The structures were established on the basis of spectroscopic evidence. The configurations of 1 and 5 were determined by X-ray analysis. The biosynthetic pathway of 1-3, 8, and 9 were proposed. Chemical transformation of aszonapyrone A (9) was also studied. Compounds 4, 5, and 7 exhibited antimalarial activity against Plasmodium falciparum, while 3, 5, and 7 showed antimycobacterial activity against Mycobacterium tuberculosis. In addition, compounds 2-7 showed cytotoxicity against cancer cell lines.     

Coibanoles, a new class of meroterpenoids produced by Pycnoporus sanguineus

Three new terpenoids of mixed biosynthetic origin were isolated from the culture filtrate of the endophytic fungus Pycnoporus sanguineus. Their structures were determined by extensive spectroscopic analyses. We have named these tricyclic and tetracyclic metabolites ‘coibanoles A-C’ in reference to Coiba Island and Coiba National Park, Panamá, from which the plant and endophyte were collected. The extract was inactive to the human parasites Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum at a test concentration of 10 μg/mL.     

Periconones B-E,new meroterpenoids from endophytic fungus Periconia sp.

Periconones B-E(1-4),four new polyketide-terpenoid hybrid molecules were isolated from the endophytic fungus Periconia sp.F-31.Their structures and absolute configurations were established by extensive spectroscopic data analysis and electronic circular dichroism(ECD).Compound 4 exhibited in vitro cytotoxic activity against the human MCF-7 tumor cell line with an IC_(50) value of 4.2 μmol/L,and compound 1 displayed anti-HIV activity with an IC_(50) value of 18.0 μmol/L.