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.     

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     

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.     

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).     

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.     

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.     

New meroterpenoids from the marine sponge Aka coralliphaga

Three new sulfated meroterpenoids containing sesquiterpene and hydroquinone moieties, namely siphonodictyal A sulfate (1), akadisulfate A (2) and akadisulfate B (3), along with the known siphonodictyal B3 and bis(sulfato)-cyclosiphonodictyol A were isolated from the sponge Aka coralliphaga. Their structures were elucidated on the basis of spectroscopic data. Akadisulfate B and siphonodictyal B3 showed a radical-scavenging activity comparable with that of the known lipophylic antioxidant BHT.     

Gymnangiamide, a cytotoxic pentapeptide from the marine hydroid Gymnangium regae

A cytotoxic aqueous extract from the marine hydroid Gymnangium regae provided a novel linear pentapeptide, designated gymnangiamide (1). The planar structure of 1 was elucidated by interpretation of spectral data as well as chemical degradation and derivatization studies. In addition to the amino acids isoleucine and phenylserine, this peptide contained N-desmethyldolaisoleuine, O-desmethyldolaproine, and alpha-guanidino serine, three residues that have not previously been reported in a natural product. The absolute configurations of the constituent amino/guanidino acids were determined by chemical degradation and derivatization, followed by HPLC and LC-MS comparison with authentic standards. Gymnangiamide (1) was moderately cytotoxic against a number of human tumor cell lines in vitro.     

Duryne,a new cytotoxic agent from the marine sponge Cribrochalinadura

Duryne, 1, a cytotoxic metabolite which inhibits the growth of both mouse and human tumor cell lines invitro has been isolated from the marine sponge Cribrochalinadura. Its structure has been assigned by spectral methods.     

Chemical-epigenetic method to enhance the chemodiversity of the marine algicolous fungus, Aspergillus terreus OUCMDZ-2739

Four new meroterpenoids identified as (R)-4-((2,2-dimethylchroman-6-yl)methyl)-3-(4-hydroxyphenyl)-5-methoxyfuran-2(5H)-one (1), 1-(2,2-dimethylchroman-6-yl)-3-(4-hydroxyphenyl)propan-2-one (2), (R,E)-3-(2,2-dimethylchroman-6-yl)-4-hydroxy-5-((2-(2-hydroxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl)methylene)furan-2(5H)-one (3), methyl (R)-2-(2-(2-hydroxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl) acetate (4), along with nine known compounds (5–13) were isolated from a chemical-epigenetic culture of Aspergillus terreus OUCMDZ-2739 with 10 μM trichostatin A (TSA). Under the same condition without TSA, A. terreus OUCMDZ-2739 produced different compounds (14–20), supporting that the chemical-epigenetic modification of fungi could enrich the chemodiversity of the fungal products. The cytotoxicity was observed for compound 8 against K562 cell, 9 against MCF-7 and K562 cells and 12 against MCF-7 cell with IC₅₀ values of 9.5, 10.1, 13.0 and 8.5 μM, respectively. Compounds 3, 8 and 17 exhibited stronger α-glucosidase inhibition than 1-deoxynojirimycin and acarbose (positive controls) with IC₅₀ values of 24.8, 1.2, 61.6, 191.7 and 555.1 μM, respectively. The enzyme kinetics study further indicated that compound 8 was an anticompetitive inhibitor with K_i value of 1.42 μM.     

Prorocentin-4, a novel linear polyketide from a marine dinoflagellate Prorocentrum sp.

Prorocentin-4, isolated from a cultured marine dinoflagellate Prorocentrum sp. was possessed of two tetrahydrofuran rings, conjugated dienes, four branched methyl groups, and a ketone moiety. The gross structure was elucidated by spectroscopic studies and the relative stereostructure was determined on the basis of spectral data.     

Cephalimysin A, a potent cytotoxic metabolite from an Aspergillus species separated from a marine fish

Cephalimysin A (1) was isolated from a strain of Aspergillus fumigatus originally separated from the marine fish Mugil cephalus, and its absolute stereostructure was elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformations including the modified Mosher’s method. This compound exhibited significant cytotoxicity against cultured P388 cells and HL-60 cells.     

Stolonidiol,a new marine diterpenoid with a strong cytotoxic activity from the Japanese soft coral

Structures of stolonidiol (1) and stolonidiol monoacetate (2), new marine diterpenoids with a strong cytotoxic activity from the Japanese soft coralClavularia sp., were established by means of spectroscopic analyses, chemical reactions, and X-ray crystallographic analysis.     

Iriomoteolide-3a, a cytotoxic 15-membered macrolide from a marine dinoflagellate amphidinium species

A 15-membered macrolide, iriomoteolide-3a (1), with an allyl epoxide has been isolated from a marine benthic dinoflagellate Amphidinium sp. (strain HYA024), and the structure was assigned by detailed analyses of 2D NMR data. Relative and absolute configurations were elucidated on the basis of conformational studies of 1 and its acetonide (2) and modified Mosher's method of 1, respectively. Iriomoteolide-3a (1) and the acetonide (2) exhibited potently cytotoxic activity against antitumor cells.     

Callyptide A,a new cytotoxic peptide from the Red Sea marine sponge Callyspongia species

In the course of our continuing efforts to allocate bioactive secondary metabolites from Red Sea marine invertebrates, we have investigated the sponge Callyspongia species. The cytotoxic dichloromethane fraction of the methanolic extract of the sponge afforded a new cytotoxic peptide named callyptide A (1). Its structure was determined by extensive 1D and 2D NMR (COSY, HSQC and HMBC) studies and high-resolution mass spectral determination. The configuration of the amino acids was determined by Marfey’s analysis. Callyptide A was found to exhibit growth inhibitory activity when tested against different cancer cell lines.     

Halichoblelides B and C,potent cytotoxic macrolides from a Streptomyces species separated from a marine fish

Halichoblelide B (1) and C (2), novel macrolides with potent cytotoxicity against tumor cells in culture, have been isolated from a strain of Streptomyces hygroscopicus originally derived from the marine fish Halichoeres bleekeri, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and chemical transformations. These compounds exhibited significant cytotoxicity against human cancer cell lines.     

Somocystinamide A, a novel cytotoxic disulfide dimer from a Fijian marine cyanobacterial mixed assemblage

[reaction: see text] Bioassay-guided investigation of the extract from a Lyngbya majuscula/Schizothrix sp. assemblage of marine cyanobacteria led to the discovery of somocystinamide A (1), an extraordinary disulfide dimer of mixed PKS/NRPS biosynthetic origin. Somocystinamide A (1) was highly acid-sensitive, rapidly and completely converting to a characterizable derivative (2). Compound 1 exhibits significant cytotoxicity against mouse neuro-2a neuroblastoma cells (IC50 = 1.4 microg/mL), whereas 2 has no activity.