Anticancer Activity of 2-O-caffeoyl Alphitolic Acid Extracted from the Lichen,Usnea barbata 2017-KL-10

Colorectal cancer is one of the life-threatening ailments causing high mortality and morbidity worldwide. Despite the innovation in medical genetics, the prognosis for metastatic colorectal cancer in patients remains unsatisfactory. Recently, lichens have attracted the attention of researchers in the search for targets to fight against cancer. Lichens are considered mines of thousands of metabolites. Researchers have reported that lichen-derived metabolites demonstrated biological effects, such as anticancer, antiviral, anti-inflammatory, antibacterial, analgesic, antipyretic, antiproliferative, and cytotoxic, on various cell lines. However, the exploration of the biological activities of lichens’ metabolites is limited. Thus, the main objective of our study was to evaluate the anticancer effect of secondary metabolites isolated from lichen (Usnea barbata 2017-KL-10) on the human colorectal cancer cell line HCT116. In this study, 2OCAA exhibited concentration-dependent anticancer activities by suppressing antiapoptotic genes, such as MCL-1, and inducing apoptotic genes, such as BAX, TP53, and CDKN1A(p21). Moreover, 2OCAA inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that 2OCAA is a better therapeutic candidate for colorectal cancer.     

Two new stereoisomers of Tetrahydrofuranoid lignans from the flower buds of Magnolia fargesii

Two new stereoisomers of tetrahydrofuranoid lignans, 7S,8R,7'S,8'R- (1) and 7R,8S,7'S,8'R-3,4,3',4'-tetramethoxy-9,7'-dihydroxy-8.8',7.O.9'-lignan (2) along with nine known lignans including tetrahydrofuranoids (3, 4) and tetrahydrofurofuranoids (5-11) were isolated from a CHCl(3)-soluble fraction of the flower buds of Magnolia fargesii. Two tetrahydrofuranoids, magnostellin A (3) and lariciresinol dimethyl ether (4) were isolated from this species for the first time. The structures of these compounds (1-11) were identified by spectroscopic methods as well as by comparison with published values. Absolute configurations of new stereoisomers (1, 2) were determined by the Mosher's esterification method and Circular Dichroism (CD) studies. All the isolates (1-11) were evaluated for their antioxidant activities using modified superoxide radical-scavenging assay. Compounds 5-8 showed the potent superoxide radical-scavenging activities with the ED(50) values of 19.2, 19.2, 16.5, and 27.7 microM, respectively, as compared with standard antioxidants (BHA: 22.8 microM; Trolox: 940 microM).     

A new flavanone glycoside from the dried immature fruits of Poncirus trifoliata

A new flavanone glycoside, (2R)-5-hydroxy-4'-methoxyflavanone-7-O-{beta-glucopyranosyl-(1-->2)-beta-glucopyranoside} (1), was isolated from the EtOAc extract of dried immature fruit of Poncirus trifoliata, together with three known compounds, (2S)-poncirin (2), (2S)-naringin (3), and (2S)-poncirenin (4). The structure of compound 1 was elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Among the isolates, compound 2 exhibited considerable inhibitory activity against lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2)) and interleukin-6 (IL-6) production, and mRNA expression in RAW 264.7 murine macrophage cells.     

18:0 Lyso PC Derived by Bioactivity-Based Molecular Networking from Lentil Mutant Lines and Its Effects on High-Fat Diet-Induced Obese Mice

Lentil (Lens culinaris; Fabaceae), one of the major pulse crops in the world, is an important source of proteins, prebiotics, lipids, and essential minerals as well as functional components such as flavonoids, polyphenols, and phenolic acids. To improve crop nutritional and medicinal traits, hybridization and mutation are widely used in plant breeding research. In this study, mutant lentil populations were generated by γ-irradiation for the development of new cultivars by inducing genetic diversity. Molecular networking via Global Natural Product Social Molecular Networking web platform and dipeptidyl peptide-IV inhibitor screening assay were utilized as tools for structure-based discovery of active components in active mutant lines selected among the lentil population. The bioactivity-based molecular networking analysis resulted in the annotation of the molecular class of phosphatidylcholine (PC) from the most active mutant line. Among PCs, 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (18:0 Lyso PC) was selected for further in vivo study of anti-obesity effect in a high-fat diet (HFD)-induced obese mouse model. The administration of 18:0 Lyso PC not only prevented body weight gain and decreased relative gonadal adipose tissue weight, but also attenuated the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and leptin in the sera of HFD-induced obese mice. Additionally, 18:0 Lyso PC treatment inhibited the increase of adipocyte area and crown-like structures in adipose tissue. Therefore, these results suggest that 18:0 Lyso PC is a potential compound to have protective effects against obesity, improving obese phenotype induced by HFD.     

Identification of a new naphthalene and its derivatives from the bulb of eleutherine americana with inhibitory activity on lipopolysaccharide-induced nitric oxide production

A new naphthoquinone, (-)-3-[2-(acetyloxy)propyl]-2-hydroxy-8-methoxy-1,4-naphthoquinone (1) was isolated from the bulb of Eleutherine americana MERR. et HEYNE (Iridaceae) together with two known compounds, eleutherinol (6) and 1,5-dihydroxy-3-methylanthraquinone (7) which were found in this species for the first time. The other known compounds, (-)-isoeleutherin (2), (+)-eleutherin (3), (-)-hongconin (4), and (+)-dihydroeleutherinol (5) which were reported previously from this species, were also isolated in the present study. Compounds 2-6 exhibited potent inhibitory activity on nitric oxide production in RAW 264.7 lipopolysaccharide-activated mouse macrophage cells with IC(50) values of 7.7, 11.4, 19.8, 21.7, and 34.4 microM, respectively, whereas the other two compounds, 1 and 7, were inactive. The structure of compound 1 was elucidated by spectroscopic data analysis including 1D and 2D NMR experiments.     

Performance Improvement of Organic Light Emitting Diodes Using Poly(N-vinylcarbazole) (PVK) as a Blocking Layer

High efficiency organic light‐emitting‐devices (OLED) have been fabricated by incorporation of a polymeric layer as a controller of the unbalanced charge. In device configuration of ITO/PEDOT:PSS/PVK/Alq₃/LiF:Al, poly(N‐vinylcarbazole) (PVK) was selected as a block‐ing layer (BL) because it has a hole transporting property and a higher band gap, especially a lower LUMO level than the emitting layer (Alq₃) and a higher HOMO level than the hole injection layer (PEDOT: PSS). As a result, the optimal structure with this bl layer showed a peak efficiency of 6.89 cd/A and 2.30 lm/W compared to the device without the PVK layer of 1.08 cd/A, 0.27 lm/W. This result shows that the PVK layer could effec‐tively block the electrons from metal cathode and confine them in the emitting layer and accomplish the charge balance, which leads to enhanced hole‐electron balance for achieving high recombination efficiency.     

A Validated LC Method for Simultaneous Determination of Phenolic, Coumarin and Phthalide Compounds in the Ethanolic Extract of Angelica tenuissima

In this study, an LC method for the simultaneous determination of six bioactive compounds from Angelica tenuissima, namely chlorogenic acid, ferulic acid, Z-ligustilide, nodakenin, decursin and decursinol angelate was developed and validated. Chromatographic analysis was carried out on a C₁₈ column with a mobile phase consisting of 0.1% formic acid, methanol and acetonitrile at a flow rate of 0.8 mL min^?1 and the effluent from the column was monitored by UV detector at 325 nm. The excellent linear behavior was observed over the investigated concentration range for reported compounds. The intra- and inter-day precision over the concentration range of compounds were lower than 1.7% (as relative standard deviation), and accuracy was between 97.2 and 106.0%. These results showed that the developed method is accurate, reproducible, and consequently applicable for the quantitation of bioactive components from the ethanolic extract of Angelica tenuissima Nakai.     

Biosynthesis of the allylmalonyl-CoA extender unit for the FK506 polyketide synthase proceeds through a dedicated polyketide synthase and facilitates the mutasynthesis of analogues

The allyl moiety of the immunosuppressive agent FK506 is structurally unique among polyketides and critical for its potent biological activity. Here, we detail the biosynthetic pathway to allylmalonyl-coenzyme A (CoA), from which the FK506 allyl group is derived, based on a comprehensive chemical, biochemical, and genetic interrogation of three FK506 gene clusters. A discrete polyketide synthase (PKS) with noncanonical domain architecture presumably in coordination with the fatty acid synthase pathway of the host catalyzes a multistep enzymatic reaction to allylmalonyl-CoA via trans-2-pentenyl-acyl carrier protein. Characterization of this discrete pathway facilitated the engineered biosynthesis of novel allyl group-modified FK506 analogues, 36-fluoro-FK520 and 36-methyl-FK506, the latter of which exhibits improved neurite outgrowth activity. This unique feature of FK506 biosynthesis, in which a dedicated PKS provides an atypical extender unit for the main modular PKS, illuminates a new strategy for the combinatorial biosynthesis of designer macrolide scaffolds as well as FK506 analogues.