Xiao-Jiang Zhou

Antifungal New Oxepine-Containing Alkaloids and Xanthones from the Deep-Sea-Derived Fungus Aspergillus versicolor SCSIO 05879

Phytopathogenic fungi remain a continuous and huge threat in the agricultural fields. The agrochemical industry has made great development of the use of microbial natural products, which has been regarded as an effective strategy against phytopathogenic fungi. Antifungal bioassay-directed fractionation was used to isolate two new oxepine-containing alkaloids (1 and 2), two new 4-aryl-quinolin-2-one alkaloids (3 and 4), and four new prenylated xanthones (5-8) from the deep-sea-derived fungus Aspergillus versicolor SCSIO 05879. Extensive NMR spectroscopic analysis, quantum mechanical calculations, and X-ray single-crystal diffraction were used to elucidate their structures, including their absolute configurations. Versicoloids A and B, versicone A, and cottoquinazoline A showed antifungal activities against three phytopathogenic fungi. The antifungal activities of these bioactive compounds strongly depend on the fungal species. Especially versicoloids A and B showed strong fungicidal effect (MIC of 1.6 μg/mL) against Colletotrichum acutatum, compared with that of the positive control cycloheximide (MIC of 6.4 μg/mL). The results of antifungal experiments indicated that versicoloids A and B may be regarded as candidate agents of antifungal agrochemicals.

Anthraquinone derivatives from Rumex plants and endophytic Aspergillus fumigatus and their effects on diabetic nephropathy.

Two new oxanthrone C-glycosides, patientosides A (14) and B (15), together with three known ones (11-13), were isolated from Rumex patientia. Their structures were identified on the basis of spectroscopic methods. The absolute configuration for 14 and 15 were deduced by analysis of their CD spectra and comparison with those of known similar compounds. Compounds 11-15, and 14 known anthraquinones (1-4, 6-10, 16-20) previously isolated from Rumex nepalensis, Rumex hastatus, and endophytic Aspergillus fumigatus, respectively, as well as a commercially available compound rhein (5) were evaluated for their inhibitory effects on IL-6 and extracellular matrix production in mesangial cells.

Five new phorbol esters with cytotoxic and selective anti-inflammatory activities from Croton tiglium

Five new phorbol esters, (four phorbol diesters, 1-4, and one 4-deoxy-4α-phorbol diester, 5), as well as four known phorbol esters analogues (6-9) were isolated and identified from the branches and leaves of Croton tiglium. Their structures were elucidated mainly by extensive NMR spectroscopic, and mass spectrometric analysis. Among them, compound (1) was the first example of a naturally occurring phorbol ester with the 20-aldehyde group. Compounds 2-5, and 7-9 showed potent cytotoxicity against the K562, A549, DU145, H1975, MCF-7, U937, SGC-7901, HL60, Hela, and MOLT-4 cell lines, with IC50 values ranging from 1.0 to 43 μM, while none of the compounds exhibited cytotoxic effects on normal human cell lines 293T and LX-2, respectively. In addition, compound 3 exhibited moderate COX-1 and COX-2 inhibition, with IC50 values of 0.14 and 8.5 μM, respectively.

Three new indolyl diketopiperazine metabolites from the antarctic soil-derived fungus Penicillium sp. SCSIO 05705

Three new indolyl diketopiperazine derivatives, penillines A and B (1 and 3), isopenilline A (2), together with seven known alkaloid compounds (E)-3-(1H-imidazole-4-yimethylene)-6-(1H-indl-3-ylmethyl)-2,5-piperazinediol (4), penilloid A (5), meleagrin (6), neoxaline (7), questiomycin A (8), N-(2-hydroxyphenyl)-acetamide (9), 2-benzoxazolinone (10), were isolated from the Antarctic soil-derived fungus Penicillium sp. SCSIO 05705. The new structures of 1–3 were elucidated on the basis of 1D and 2D NMR, mass spectra, CD spectra, and quantum chemical calculations. All the isolated compounds were tested for their antiviral (H1N1 and H3N2), antituberculosis, antibacterial, and cytotoxic activities. Among them, compounds 6–8 had significant in vitro cytotoxicities against the K562, MCF-7, A549, U937, Hela, DU145, HL60, and HT29 cell lines, with IC50 values ranging from 2.73 to 17.7 μM. In addition, compound 8 showed potent antituberculosis activity with an MIC value of 3.91 μM, and the inhibition effect was close to the positive control INH (isoniazid, MIC 2.04 μM). A possible biogenesis pathway for compounds 1–7 was proposed.

Dicarabrol, a new dimeric sesquiterpene from Carpesium abrotanoides L.

A new dimeric sesquiterpene, dicarabrol (1), together with three known sesquiterpenes, carabrol (2), 11(13)-dehydroivaxillin (3), and 2-desoxy-4-epi-pulchellin (4), were isolated from the whole plant of Carpesium abrotanoides L. Their structures were elucidated on the basis of spectroscopic analysis, and single crystal X-ray diffraction analysis. Compound 1 possessed a dimeric sesquiterpene core featured with a cyclopentane ring connecting two sesquiterpene lactone units rarely discovered in nature. Dicarabrol (1), as well as three known sesquiterpenes (2-4), had potent in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U937, H1975, SGC-7901, A549, MOLT-4, and HL60 cell lines with IC50 values ranging from 0.10 to 46.7 μM, while they showed significant antiviral (H1N1 and H3N2) activities. Furthermore, compounds 1, 3 and 4 displayed significant antimycobacterial activity (IC50 3.7, 6.0, and 7.6 μM, respectively).

Quinone/hydroquinone meroterpenoids with antitubercular and cytotoxic activities produced by the sponge-derived fungus Gliomastix sp. ZSDS1-F7

Abstract Fifteen compounds, including six quinone/hydroquinone meroterpenoids, purpurogemutantin (1), macrophorin A (2), 4′-oxomacrophorin (3), 7-deacetoxyyanuthone A (4), 2,3-hydro-deacetoxyyanuthone A (5), 22-deacetylyanuthone A (6), anicequol (7), three roquefortine derivatives, roquefortine C (8), (16S)-hydroxyroquefortine C (9), (16R)-hydroxyroquefortine C (10), dihydroresorcylide (11), nectriapyrone (12), together with three fatty acid derivatives, methyl linoleate (13), phospholipase A2 (14), methyl elaidate (15), were isolated from the sponge-derived fungus Gliomastix sp. ZSDS1-F7 isolated from the sponge Phakellia fusca Thiele collected in the Yongxing island of Xisha. Their structures were elucidated mainly by extensive NMR spectroscopic and mass spectrometric analyses. Among these compounds, compounds 1–3 and 5–7 showed significant in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U937, H1975, SGC-7901, A549, MOLT-4 and HL60 cell lines, with IC50 values ranging from 0.19 to 35.4 μM. And compounds 2–4 exhibited antitubercular activity with IC50 values of 22.1, 2.44 and 17.5 μM, respectively. Furthermore, compound 7 had anti-enterovirus 71 activity with MIC value of 17.8 μM. To the best of our knowledge, this is the first report to product two quinone/hydroquinone meroterpenoids skeletons (linear skeleton and drimane skeleton) from the same fungal strain.

Characterization and biological evaluation of six new dimeric lignans with an unusual alpha,beta-unsaturated ketone motif from Zanthoxylum simulans

Investigation of the bark of Zanthoxylum simulans afforded six new dimeric lignans zanthpodocarpins C-H (1-6) bearing an unusual α,β-unsaturated ketone group. The new structures of 1-6 were determined by using detailed spectroscopic analysis. All of the isolated compounds were examined for their inhibitory effects against rat joint synovial cell and splenocyte proliferation. Compounds 1-6 showed potent anti-inflammatory activities with IC50 values ranging from 18.6 to 36.1μM, and 13.8 to 74.3μM.

Ochracenes A–I, Humulane-Derived Sesquiterpenoids from the Antarctic Fungus Aspergillus ochraceopetaliformis

Nine new humulane-derived sesquiterpenoids, ochracenes A-I (1-9), were isolated from the Antarctic fungus Aspergillus ochraceopetaliformis SCSIO 05702. Their structures including absolute configurations were elucidated on the basis of spectroscopic analysis, Moshers method, and electronic circular dichroism analysis. Compared with previous humulane-type sesquiterpenoids, ochracenes A-I (1-9) featured novel carbon skeletons with corresponding methyl migration, ring cleavage, and carbon loss. Two unprecedented 8,9-secocyclic sesquiterpenoids (2 and 3) exhibited inhibitory effects on lipopolysaccharide-induced NO release in RAW 264.7 mouse macrophage cell lines with IC50 values of 14.6 ± 0.5 and 18.3 ± 1.7 μM, respectively.

One Strain-Many Compounds Method for Production of Polyketide Metabolites Using the Sponge-Derived Fungus Arthrinium arundinis ZSDS1-F3

[Li, Yinglei; Wang, Junfeng; He, Weijun; Lin, Xiuping; Liu, Yonghong] Chinese Acad Sci, South China Sea Inst Oceanol, Key Lab Trop Marine Bioresources & Ecol,Microbiol, Guangdong Key Lab Marine Mat Med,RNAM Ctr Marine, Guangzhou 510301, Guangdong, Peoples R China; [Li, Yinglei] Univ Chinese Acad Sci, Beijing 100049, Peoples R China; [He, Weijun; Zhou, Xiaojiang] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Hunan, Peoples R China

Isoquinoline alkaloids from Zanthoxylum simulans and their biological evaluation.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial inflammation, destruction of joint cartilage and bone erosion, it affected 0.5 to 1% of the population.1–4 At the present, the treatment of RA often involves the extensive use of disease-modifying anti-rheumatic drugs and anti-rheumatic biological drugs, such as methotrexate, salazosulfapyridine, iguratimod, tofacitinib and so on.5–7 However, more attention has been focused on traditional Chinese medicine by their efficacy against RA and safety, for example, sinomenine that is extracted from Sinomenium acutum has shown therapeutic efficacy and few side effects in patients with RA in China since the 1990s.8,9 Natural products have provided unlimited opportunities for new drug discoveries because of their inherent chemical diversity, and have prompted a continuous research for plant sources with medicinal value. Zanthoxylum simulans belongs to the genus Zanthoxylum of Rutaceae family. The barks are commonly used for the treatment of RA and swelling with unknown reasons in traditional Chinese medicine.10 Previous chemical investigations on this genus have led to the identification of a series of alkaloids, coumarins, amides, lignans and flavonoids.11–15 However, the specific components responsible for the therapeutic effects of this traditional Chinese medicine are still not well clarified. In our ongoing study to seek bioactive constituents from this traditional Chinese medicine against RA, we isolated a series of isoquinoline alkaloids, including three new alkaloids, zanthoxylumines A–C (1–3), together with six known compounds (Figure 1), 6-acetonyl-N-methyldihydrodecarine (4),16 8-hydroxy-7-methoxy-5-methyl-2,3-meth-ylenedioxybenzo[c] phenanthridin-6(5H)-one (5),17 decarine (6),18 norchelerythrine (7),18 liriodenine (8)19 and lysicamine (9).19 Their structures were elucidated using extensive spectroscopic techniques. The isolated compounds were evaluated for their inhibitory activities against rat joint synovial cell proliferation, splenocyte proliferation and antimicrobial activities. We present herein the extraction, isolation, structure elucidation and biological activities of compounds 1–9. Compound 1 was obtained as white solid, and had a molecular formula C19H15NO4 from the high resolution electron ionization mass spectra (HREIMS) (m/z 321.0992 [M]+, calcd 321.1001). The 1H and 13C NMR data (Table 1) showed the characteristic pattern of a benzophenanthridine alkaloid.16–18 The 1H NMR spectrum exhibited signals at δH 7.56 (d, J= 8.9 Hz), 8.40 (d, J= 8.9 Hz), 8.41 (d, J= 8.9 Hz), 7.84 (d, J= 8.9 Hz), 7.31 (s), 8.62 (s) and 9.58 (s), indicating the presence of four aromatic hydrogens in ortho position and three isolated hydrogens, and it can be confirmed by the crosspeaks between H-9 (δH 7.56 ) and H-10 (δH 8.40), H-11 (δH 8.41) and H-12 (δH 7.84) in the 1H–1H COSY spectrum. Detailed analysis of the one-dimensional and two-dimensional NMR spectra data revealed that the NMR data of 1 were very similar to those of decarine (6),18 except for the signals for the methylenedioxide group in decarine (6) were replaced by those for one methoxy group and one hydroxyl group in compound 1. The methoxy group was assigned by the correlation from 3-OCH3 to C-3 in the HMBC spectrum (Figure 2). The ROESY spectrum showed the correlations between protons H-12 and H-1/H-11, H-9 and H-10 (Figure 2). Therefore, compound 1 was elucidated as 2,8-dihydroxy-3,7-dimethoxybenzo[c]phenanthridine and named zanthoxylumine A. Compound 2 was isolated as white solid. Its molecular formula was determined as C20H17NO4 on the basis of the HREIMS (m/z 335.1155 [M]+, calcd 335.1158). The 1H and 13C NMR data (Table 1) indicated that the structure of 2 was closely similar to that of 1, differing in one more O-methyl in the structure of 2, which was also supported by the correlation from 2-OCH3 to C-2 in the HMBC spectrum (Figure 2). The ROESY spectrum showed the correlations between protons H-12 and H-1/H-11, H-9 and H-10 (Figure 2). Thus, compound 2 was