Berkeleylactones S-T, novel 16-membered macrolides isolated from the endophytic fungus Penicillium egyptiacum.

The fungus Penicillium egyptacum has been reported as a producer of the 16-membered macrolide antibiotic A26771B. In this study, two new berkeleylactone analogues, berkeleylactones S-T (1-2), were isolated from P. egyptiacum. Their structures were determined by the analyses of 1D- and 2D-NMR data, HRESIMS, and chemical derivatization. 1 is the first example of berkeleylactone analogue possessing a glucose moiety, whose absolute configuration was elucidated by acid hydrolysis followed by derivatization and LC-MS analysis. No antibacterial activity against Bacillus subtilis and Streptococcus salivarius was found within the range of 0-100 µM for compounds 1-2.

Two pairs of 2-pyrone enantiomers and a benzophenone analogue from the endophytic fungus Penicillium egyptiacum.

Four new 2-pyrone derivatives, two pairs of enantiomers, (±)-egypyrone A [(±)-1] and (±)-egypyrone B [(±)-2], together with a new benzophenone analogue, orbiophenone B (3), were isolated from the endophytic fungus Penicillium egyptiacum. The enantiomeric mixtures (±)-1 and (±)-2 were separated through chiral HPLC, respectively. Their structures were elucidated by extensive analysis of spectroscopic data and the absolute configuration was determined by comparing the optical rotation of structurally similar molecule. Subsequently, the cytotoxic activities of (±)-1, (±)-2, and 3 against the U87 cell line were tested and no activity was observed at a concentration of 10 µM.

Gene mining and efficient biosynthesis of a fungal peptidyl alkaloid.

Objective: Peptidyl alkaloids, a series of important natural products can be assembled by fungal non-ribosomal peptide synthetases (NRPSs). However, many of the NRPSs associated gene clusters are silent under laboratory conditions, and the traditional chemical separation yields are low. In this study, we aim to discovery and efficiently prepare fungal peptidyl alkaloids assembled by fungal NRPSs. Methods: Bioinformatics analysis of gene cluster containing NRPSs from the genome of Penicillium thymicola, and heterologous expression of the putative gene cluster in Aspergillus nidulans were performed. Isolation, structural identification, and biological evaluation of the product from heterologous expression were carried out. Results: The putative tri-modular NRPS AncA was heterologous-expressed in A. nidulans to give anacine (1) with high yield, which showed moderate and selective cytotoxic activity against A549 cell line. Conclusion: Heterologous expression in A. nidulans is an efficient strategy for mining fungal peptidyl alkaloids.

Six new monacolin analogs from red yeast rice.

Six novel monacolin analogs, monacolins V1-V6 (1-6), together with seven known ones (7-13), were isolated from the ethyl acetate extract of red yeast rice. Their structures and absolute configurations were determined by spectroscopic methods, especially 2D NMR (1H-1HCOSY, HSQC, HMBC, and NOESY/ROESY) and CD spectroscopic analyses as well as chemical derivation. Monacolins V2 (2) and V3 (3) represent the first examples of monacolins with 3-hydroxybutyrate substitute. The anti-inflammatory inhibitory activities against the lipopolysaccharide (LPS) induced NO production in BV-2 cells as well as antioxidant activities against rat liver microsomal lipid peroxidation were evaluated.

Diphenyl Ethers from a Marine-Derived Aspergillus sydowii.

Six new diphenyl ethers (1⁻6) along with eleven known analogs were isolated from the ethyl acetate extract of a marine-derived Aspergillus sydowii guided by LC-UV-MS. Their structures were unambiguously characterized by HRESIMS, NMR, as well as chemical derivatization. Compounds 1 and 2 are rare diphenyl ether glycosides containing d-ribose. The absolute configuration of the sugar moieties in compounds 1⁻3 was determined by a LC-MS method. All the compounds were evaluated for their cytotoxicities against eight cancer cell lines, including 4T1, U937, PC3, HL-60, HT-29, A549, NCI-H460, and K562, and compounds 1, 5, 6, and 8⁻11 were found to exhibit selective cytotoxicity against different cancer cell lines.

[Trace phenolic compounds from Red Yeast Rice].

Trace chemical constituents from the ethyl acetate extract of Red Yeast Rice were investigated. Four phenolic compounds were isolated by various column chromatographies, and their structures were identified on the basis of spectroscopic analysis including UV, MS, IR and NMR. The four compounds were identified as 2-methyl-5-(2'R-methyl-4'-hydroxy-butyl)-cinnamic acid(1), 5-(2'-hydroxy-6'-methyl phenyl)-3-methylfuran-2-carboxylic acid(2), daidzein(3), and genistein(4). Compound 1 was new and 2 was firstly discovered from the genus Monascus, while 3-4 were obtained from Red Yeast Rice for the first time.

Highly Photosensitive Poly-Sulfur-Bridged Chetomin Analogues from Chaetomium cochliodes.

The highly photosensitive characteristic of poly-sulfide chetomins was first unveiled, and four new unstable analogues, chetomins A-D (1-4), with significant cytotoxicity were successfully purified in darkness. The visible-light-induced desulfurization and intermolecular disproportionation were revealed to initiate the interconversion of chetomin analogues, which explained the long-recognized puzzle of rarity and instability of chetomin analogues.

Bysspectin A, an unusual octaketide dimer and the precursor derivatives from the endophytic fungus Byssochlamys spectabilis IMM0002 and their biological activities.

Bysspectin A (1), a polyketide-derived octaketide dimer with a novel carbon skeleton, and two new precursor derivatives, bysspectins B and C (2 and 3), were obtained from an organic extract of the endophytic fungus Byssochlamys spectabilis that had been isolated from a leaf tissue of the traditional Chinese medicinal plant Edgeworthia chrysantha, together with a known octaketide, paecilocin A (4). Their structures were determined by HRMS, 1D and 2D NMR spectroscopic analysis. A plausible route for their biosynthetic pathway is proposed. Compounds 1-3 were tested for their antimicrobial activities. Only compound 3 was weakly active against Escherichia coli and Staphyloccocus aureus with MIC values of 32 and 64 µg/mL, respectively. Further, the inhibitory effects on human carboxylesterases (hCE1, hCE2) of compounds 1 and 4 were evaluated. The results demonstrated that bysspectin A (1) was a novel and highly selective inhibitor against hCE2 with the IC50 value of 2.01 µM. Docking simulation also demonstrated that active compound 1 created interaction with the Ser-288 (the catalytic amino-acid in the catalytic cavity) of hCE2 via hydrogen bonding, revealing its highly selective inhibition toward hCE2.

Phloroglucinols with Antioxidant Activities Isolated from Lysidice rhodostegia.

Two new phloroglucinols, lysidisides X and Y (1 and 2), and two known compounds, 2-(2-methylbutyryl)phloroglucinol 1-O-ß-d-glucopyranoside (3) and (E)-resveratrol 3-(6″-galloyl)-O-ß-d-glucopyranoside (4), have been isolated from the roots of Lysidice rhodostegia. The structures of 1 and 2 were elucidated primarily by NMR experiments. Their absolute configurations were deduced via circular dichroism (CD) data and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 exhibited significant antioxidative activities with IC50 values of 12.0 and 11.8 µM, respectively.

Cytotoxic cardenolides from the stems of Periploca forrestii.

Six new cardenolides, periforosides D-E (1-2), periforgenin C (3) and periforosides F-H (4-6), as well as 10 previously identified cardenolides (7-16) were isolated from the ethanol extract of the stems of Periploca forrestii. The structures of the new compounds were determined using extensive spectroscopic analyses including HRESI-MS, 1D and 2D NMR data. Evaluation of the cytotoxic activity of all the isolated compounds in five different human cancer cell lines indicated that compounds 2-6, 8, 9 and 12-16 have potent activity.

Prenylated C6-C3 compounds with molecular diversity from the roots of Illicium oligandrum.

Eleven prenylated C(6)-C(3) compounds, illioliganpyranone A (1), illioliganfunone A-D (2-5), and illioliganone D-I (6-11), together with five known prenylated C(6)-C(3) compounds (12-16), were isolated from roots of Illicium oligandrum. The structures of 1-11 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and CD experiments. Possible biosynthetic pathways to compounds 1-16 derived from a common precursor of 5-allylbenzene-1,2,4-triol were postulated. All compounds were evaluated for cytotoxic activities against five human cancer cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780). Compound 15 exhibited significant cytotoxicity against HCT-8, BGC-823, A549, and A2780 cell lines with IC(50) values of 0.30-2.57 µM. Compound 16 showed moderate selective cytotoxicity against sensitive A2780 cells with IC(50) value of 1.38 µM.

Phenolic glycosides isolated from the bark of Lysidice brevicalyx Wei.

Two new compounds, lysidiside S (1) and 7-O-(+)-peltogynol-beta-d-glucopyranoside (2), together with six known phenolic glycosides (3-8) were isolated from the bark of Lysidice brevicalyx Wei. The structures of these compounds were characterized by chemical and spectroscopic methods. The antioxidant activities of compounds 1-8 were evaluated, and compound 3 exhibited remarkable antioxidant activity at concentrations of 10(-4), 10(-5), and 10(-6) mol/l.

Lysidicins F-H, three new phloroglucinols from Lysidice rhodostegia.

Three new phloroglucinols, named lysidicins F-H (1-3), were isolated from the roots of Lysidice rhodostegia. These compounds have a unprecedented benzyl benzo[b]furo[3,2-d]furan skeleton, and lysidicin F (1) is the first example of natural product with trans-fused furan rings. Their structures were established on the basis of extensive spectroscopic analysis, and the absolute configurations of them were determined by computational methods. A possible biosynthetic pathway for 1-3 was also postulated.

Structural characterization of constituents with molecular diversity in fractions from Lysidice brevicalyx by liquid chromatography/diode-array detection/electrospray ionization tandem mass spectrometry and liquid chromatography/nuclear magnetic resonance.

A combination of electrospray ionization tandem mass spectrometry with high-performance liquid chromatography (HPLC/ESI-MSn), and hyphenation of liquid chromatography to nuclear magnetic resonance spectroscopy (HPLC/NMR), have been extensively utilized for on-line analysis of natural products, analyzing metabolite and drug impurity. In our last paper, we reported an on-line analytical method for structural identification of trace alkaloids in the same class. However, the structural types of the constituents in plants were various, such as flavanoids, terpenoids and steroids. It is important to establish an effective analytical method for on-line structural identification of constituents with molecular diversity in extracts of plants. So, in the present study, the fragmentation patterns of some isolated stilbenes, phloroglucinols and flavanoids from Lysidice rhodostegia were investigated by ESI-MSn. Their fragmentation rules and UV characteristics are summarized, and the relationship between the spectral characteristics, rules and the structures is described. According to the fragmentation rules, NMR and UV spectral characteristics, 24 constituents of different types in the fractions from L. brevicalyx of the same genus were structurally characterized on the basis of HPLC/HRMS, HPLC-UV/ESI-MSn, HPLC/1H NMR and HPLC/1H-1H COSY rapidly. Of these, six (10, 13, 14, 16, 17 and 23) are new compounds and all of them are reported from L. brevicalyx for the first time. The aim is to develop an effective analytical method for on-line structural identification of natural products with molecular diversity in plants, and to guide the rapid and direct isolation of novel compounds by chemical screening.

Cytotoxic triterpenoid saponins acylated with monoterpenic acid from Pithecellobium lucidum.

Three new oleanane-type triterpene saponins, named pithelucosides A-C (1-3), together with two known saponins (4, 5) were isolated from the roots of Pithecellobium lucidum. The structures of the new saponins were established on the basis of extensive 1D and 2D NMR experiments and mass spectrometry and confirmed by acid and alkaline hydrolysis. Compounds 1-5 and 7 (pro-sapogenin obtained from the mild alkaline hydrolysate of 1) were evaluated for cytotoxic activity on five human tumoral cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780) and for hemolytic property against rabbit erythrocytes. Compounds 2-5 showed significant cytotoxic activities with IC50 values of 0.61-7.56 microM. All tested compounds did not exhibit any hemolytic activity in the concentration range 0.01-100 microM.

Glucosides from the roots of Capparis tenera.

Two new lignan glucosides, compounds 2 and 3, two new 1H-indole-alkaloid glucosides, 5 and 6, as well as two new phenolic glucosides, 7 and 10, were isolated from the roots of Capparis tenera, together with five known compounds. Their structures were characterized by chemical and spectroscopic methods. Most of these isolates were obtained for the first time from Capparidaceae. The antioxidant and anti-inflammatory activities of the new compounds were investigated.

Two new compounds from the roots of Lysidice rhodostegia.

Two new compounds, lysidicin D (1) and lysidicin E (2), were isolated from the roots of Lysidice rhodostegia. Their structures were elucidated by means of spectroscopic methods. Among them compound 1 showed potent anti-oxidant activity on in vitro.

[Studies on chemical constituents of Cynanchum forrestii].

OBJECTIVE: To study the chemical constituents of Cynanchum forrestii. METHOD: Chromatographic techniques were applied to isolated chemical constituents. The structures were identified on the basis of physico-chemical constants and spectroscopic data. RESULT: Eight compounds were isolated from the 95% ethanol extract of the roots of C. forrestii and elucidated as ( + ) -5'-methoxyisolariciresinol 3a-O-beta-D-glucopyranoside (1), hexahydroxycholest-7-en-6-one (2), tylophorinidine (3), sucrose (4), palmitic acid (5), beta-sitosterol (6), daucosterol (7), nonanedioic acid (8). CONCLUSION: Compounds 1-3 from this genus, and compounds 4-8 from the plant were obtained for the first time.

[Studies on chemical constituents from roots of Craibiodendron henryi].

OBJECTIVE: To study the chemical constituents from the roots of Craibiodendron henryi. METHOD: Various chromatographic techniques were used to isolate and purify the constituents. The structures were elucidated by chemical evidence and spectral methods. RESULT: Twelve compounds were isolated from the ethyl acetate soluble fraction of the 95% ethanolic extract and their struc- tures were elucidated as quercetin (1), quercetin-3-O-rhamnicoside (2), quercetin-3-O-arabinofuranoside (3), (-)-epicatechin (4), proanthocyanidin A-2 (5), procyanidin B-2 (6), (-)-isolariciresinol-2a-O-beta-D-xylopyranoside (7), lyoniside (8), sitoster-yl-3beta-glucoside-6'-O-palmitate (9), beta-sitosterol (10), daucosterol (11) and octacosanoic acid (12). CONCLUSION: Compounds 1-12 were isolated from this plant for the first time.

Structure-activity studies of phenanthroindolizidine alkaloids as potential antitumor agents.

Five phenanthroindolizidine alkaloids (PA) were chemically synthesized and seven were isolated from Tylophora atrofolliculata. To facilitate future drug design of phenanthroindolizidine alkaloids as potential antitumor agents, we have explored the structure-activity relationships (SAR) of this class of compounds. We demonstrated that DCB-3503 and tylophorinidine (PA-7) were among the most active compounds against tumor growth both in vitro and in vivo. In the hepatocellular carcinoma cell line HepG2, the GI(50)s of DCB-3503 and PA-7 were 35+/-5 nM and 11+/-5 nM, respectively. DCB-3503 and PA-7 significantly inhibited HepG2 tumor growth in nude mice at a dose of 9 mg/kg given by intraperitoneal (ip) injections twice a day every third day for a total of four cycles (P<0.05 for DCB-3503 and P<0.01 for PA-7). Their potent antitumor activities correlated with their potent NF-kappaB-inhibitory effects and their cyclin D1 down-regulatory effects.