Spectroscopic Methods Research Articles

Structural characterization of two new stereoisomeric furofuran lignans using modern spectroscopic methods and quantum chemical calculation

C. arborea Roxb stems yielded two new compounds callicarbonans A and B (1–2), optically active with specific rotations of [α] 25.0 D-14.0, and [α] 25.0 D+4.8, along with thirteen (3–15) reported compounds. Their structures were characterized by contemporary spectroscopic techniques, encompassing 1D (1H, 13C, DPET) and 2D (HSQC, HMBC, 1H–1H COSY, and ROESY) NMR, HR-ESI-MS, UV, IR, ECD. Their absolute configurations (AC) were confirmed through quantum chemical computations, and Diastereomeric Parameter 4 Plus (DP4+) analysis was utilized to identify their relative configurations. The cytotoxicity of all compounds was assessed against cancer cells. Specifically, diterpenoid 13 showed cytotoxic effects against MDA-MB-231, SW620, and HepG2 cancer cells with IC50 values of 20.34±0.89, 20.17±0.95, and 22.72±0.96 µM, respectively.

Purification, Molecular Docking and Cytotoxicity Evaluation of Bioactive Pentacyclic Polyhydroxylated Triterpenoids from Salvia urmiensis.

Triterpenoids, as one of the largest classes of naturally occurring secondary metabolites in higher plants, are of interest due to their high structural diversity and wide range of biological activities. In addition to several promising pharmacological activities such as antimicrobial, antiviral, antioxidant, anti-inflammatory and hepatoprotective effects, a large number of triterpenoids have revealed high potential for cancer therapy through their strong cytotoxicity on cancer cell lines and, also, low toxicity in normal cells. So, this study was aimed at discovering novel and potentially bioactive triterpenoids from the Salvia urmiensis species. For this, an ethyl acetate fraction of the acetone extract of the aerial parts of the plant was chromatographed to yield five novel polyhydroxylated triterpenoids (1: -5: ). Their structure was elucidated by extensive spectroscopic methods including 1D (1H, 13C, DEPT-Q) and 2D NMR (COSY, HSQC, HMBC, NOESY) experiments, as well as HRESIMS analysis. Cytotoxic activity of the purified compounds was also investigated by MTT assay against the MCF-7 cancer cell line. Furthermore, a molecular docking analysis was applied to evaluate the inhibition potential of the ligands against the nuclear factor kappa B (NF-κB) protein, which promotes tumor metastasis or affects gene expression in cancer disease. The 1β,11β,22α-trihydroxy-olean-12-ene-3-one (compound 4: ) indicated the best activity in both in vitro and in silico assays, with an IC50 value of 32 µM and a docking score value of - 3.976 kcal/mol, respectively.

Secondary metabolites from Centaurea diluta Ait. subsp. Algeriensis (Coss. & Dur.)

The phytochemical investigation of the aerial parts of Centaurea diluta Ait. subsp. Algeriensis (Coss. & Dur.) led to the isolation of nine secondary metabolites: β-sitosterol (1), six flavonoids: eupatilin (2), jaceosidin (3), pectolinaringenin (4), galetin 3,6-dimethyl ether (5), hispiludin (6), and quercetin (9), one coumarin: scopoletin (7), and one sesquiterpene lactone: cebelin G (8). Spectroscopic methods such as 1H and 13C NMR, COSY, NOESY, HSQC, and HMBC studies, as well as comparison with literature data, were used to identify the structures. Apart from the constituents eupatilin and jaceosidin, the other compounds are new for the species Centaurea diluta Ait. subsp. Algeriensis (Coss. & Dur.). The chemotaxonomic significance of the isolates was discussed.

Radical scavenging dihydroxycinnamic natural compounds from Trianthema pentandra

BackgroundTrianthema pentandra is a promising plant with numerous medical applications. Previous studies have confirmed that the plant is strongly cytotoxic in brine shrimp lethality tests and has antibacterial effects. However, the compounds responsible for these biological activities have not been identified. This study aimed to screen plants in an antiradical assay using 1,1-diphenyl-2-picrylhydrazyl (DPPH). This assay was used to guide the isolation of active compounds, which were identified at the molecular structural level by spectroscopic methods. MethodsThe plant was extracted using ethanol, labelled F1 and fractionated by solvents of different polarities (F2 chloroform, F4 ethyl acetate, F5 aqueous methanol, and F6 n-hexane). The ethyl acetate and aqueous methanol (F4 and F5) fractions were selected for further purification based on their yields and activities. They were run on chloroform-methanol and n-hexane-ethyl acetate gradients, respectively. Fractions resulting from column chromatography were further screened for DPPH antioxidant activity, upon which fraction F5–1–077 had unusually high activity (IC50 = 3.57 µg/ml). Further purification of these fractions through recrystallization and high-performance liquid chromatography (HPLC) led to the isolation of three compounds. Results: Among these compounds, two were identified and characterized using FT-IR, LC-MS, and complete nuclear magnetic resonance (NMR) data, and 2,3-dihydroxycinnamic acid ethyl ester and its analog acid were isolated from the ethyl acetate fraction (F4). The former compound has been proven to have good activity in comparison with standards, ascorbic acid, and butylated hydroxytoluene (BHT), even at a low concentration of 5 µg/ml with an IC50 value of 0.13 µg/ml in the DPPH assay. The molecular docking data supported the potent activity of the compound with binding affinity, ∆G = -6.4 kcal/mol compared to the ascorbic acid (∆G = -5.0 kcal/mol) used as standard. ConclusionThis study serves as a groundbreaking foundation for the investigation of the natural dihydroxycinnamic compounds present in this plant.

Antiprotozoal potential of Vismia species (Hypericaceae), medicinal plants used to fight cutaneous leishmaniasis

Ethnopharmacological relevanceSpecies of Vismia (Hypericaceae), known in Brazil as “lacre”, are commonly used in traditional Amazonian medicine for the treatment of skin lesions, including those caused by Leishmania infection. Aim of the studyHexane extracts from the leaves of Vismia cayennensis, V. gracilis, V. sandwithii and V. guianensis, as well as from the fruits of the latter, in addition to the anthraquinones vismiaquinone, physcion and chrysophanol isolated from these species were explored for their anti-promastigote and anti-amastigote activity on Leishmania amazonensis. Materials and methodsExtracts were prepared by static maceration with n-hexane. The compounds, isolated by chromatographic techniques, were identified by spectroscopic methods (1H and 13C NMR). Promastigotes of L.amazonensis were incubated with hexane extracts (1–50 μg/mL) or anthraquinones (1–50 μM) and the parasite survival analyzed. The action of compounds on reactive oxygen species (ROS) production, mitochondrial membrane potential, and membrane integrity of promastigotes were evaluated by flow cytometer, and the cytotoxicity on mammalian cells using MTT assay. Furthermore, the activity of compounds against amastigotes and nitric oxide production were also investigated. ResultsVismiaquinone and physcion were obtained from the leaves of V. guianensis. Physcion, as well as chrysophanol, were isolated from V. sandwithii. Vismia cayennensis and V. gracilis also showed vismiaquinone, compound detected in lower quantity in the fruits of V. guianensis. All extracts were active against the parasite, corroborating the popular use. The greatest activity against promastigotes was achieved with V. guianensis extract (IC50 4.3 μg/mL), precisely the most used Vismia species for treating cutaneous leishmaniasis. Vismiaquinone and physcion exhibited relevant activity with IC50 12.6 and 2.6 μM, respectively. Moreover, all extracts and anthraquinones tested induced ROS production, mitochondrial dysfunction, membrane disruption and were able to kill intracellular amastigote forms, being worthy of further in vivo studies as potential antileishmanial drugs. ConclusionsThe overall data achieved in the current investigation scientifically validate the traditional use of Vismia species, mainly V. guianensis, as an anti-Leishmania agent. Furthermore, the promising results presented here indicate species of Vismia as potentially useful resources of Brazilian flora for the discovery of therapeutic solutions for neglected diseases.

Cytotoxic and antimicrobial metabolites from the marine-derived fungus Aspergillus sp. OPR23-FS01

Chemical investigation of a marine-derived fungus Aspergillus sp. OPR23-FS01 resulted in the isolation of a new unsaturated fatty acid featuring a terminal olefin, 10-methoxy-2-methylene-10-oxodecanoic acid (1), two new natural compounds, 2-carboxy-2′-methyl-azobenzene (2) and 1,3,9-trimethyluric acid (3), and 11 previously described metabolites, pantheric acid C (4), pantheric acid D (5), 2-furoic acid (6), 5-(hydroxymethyl)-2-furancarboxylic acid (7), sporogen-AO 1 (8), gliocladic acid (9), hydroheptelidic acid (10), ditryptophenaline (11), emodin (12), uridine (13), and thymidine (14). Their structures were identified by comprehensive analyses of the spectroscopic methods, including NMR and HRESI mass spectra. Compound 2 possesses a rare diazenyl group among the previously reported fungal metabolites. Compound 8 showed significant cytotoxicity against both HepG2 and MCF-7 cell lines in a dose-dependent manner, with IC50 values of 4.66 ± 0.24 and 5.54 ± 0.28 μM, respectively. Compounds 1−5 and 8−11 displayed antimicrobial effect against Enterococcus faecalis ATCC299212, with MIC values ranging from 32 to 128 μM, whereas 1, 4, 5, and 8−11 inhibited Candida albicans ATCC10231 growth, with MIC values in a range of 32–256 μM.

Identification and quantification of chain-pairing variants or mispaired species of asymmetric monovalent bispecific IgG1 monoclonal antibody format using reverse-phase polyphenyl chromatography coupled electrospray ionization mass spectrometry

Developing a knob-into-hole asymmetric bispecific IgG1 monoclonal antibody (mAb) poses manufacturing challenges due to the expression of chain pairing variants, also called mispaired species, in the desired product. The incorrect pairing of light and heavy chains could result in heterogeneous mispaired species of homodimers, heterodimers, light chain swapping, and low molecular weight species (LMWS). Standard chromatography, capillary electrophoretic, or spectroscopic methods poorly resolve these from the main variants. Here, we report a highly sensitive reverse-phase polyphenyl ultra-high-performance liquid chromatography (RP-UHPLC) method to accurately measure mispaired species of Duet mAb format, an asymmetric IgG1 bispecific mAb, for both process development and quality control analytical tests. Coupled with electrospray ionization mass spectrometry (ESI-MS), it enabled direct online characterization of mispaired species. This single direct assay detected diverse mispaired IgG-like species and LMWS. The method resolved eight disulfide bonds dissociated LMWS and three mispaired LMWS. It also resolved three different types of IgG-like mispaired species, including two homodimers and one heterodimer. The characterization and quantification simultaneously enabled the cell line selection that produces a lesser heterogeneity and lower levels of mispaired species with the desired correctly paired product. The biological activity assessment of samples with increased levels of these species quantified by the method exhibited a linear decline in potency with increasing levels of mispaired species in the desired product. We also demonstrated the utility of the technique for testing in-process intermediate materials to determine and assess downstream purification process capability in removing diverse mispaired IgG-like species and LMWS to a certain level during the downstream purification process. Our investigation demonstrates that adopting this method was vital in developing asymmetric bispecific mAb from the initial stage of cell line development to manufacturing process development. Therefore, this tool could be used in the control strategy to monitor and control mispaired species during manufacturing, thus improving the quality control of the final product.

Variability of Isoquinoline Alkaloid Profiles and Anticholinesterase Activities with Binding-Mode Predictions of Glaucium flavum Population.

In this study, phytochemical and biological activity studies supported by docking were carried out on a species of the genus Glaucium, a repository of isoquinoline alkaloids. The GC-MS (Gas Chromatography-Mass Spectrometry) method is used to characterize the isoquinoline alkaloids of Glaucium flavum Crantz. (Papaveraceae). G. flavum was collected from seven different regions of Türkiye (Antalya, Urla-Izmir, Mordogan-Izmir, Mugla, Assos-Canakkale, Karabiga-Canakkale, Giresun) and totally 17 compounds were detected by GC-MS. Glaucine was found to be the major constituent in the sample collected from Mugla, whereas isocorydine was recorded to be the principal alkaloid in other samples. Further fractionation studies on G. flavum collected from Antalya province in Southwestern Türkiye, yielded five major alkaloids (isocorydine 1, dihydrosanguinarine 2, glaucine 3, dehydroglaucine 4, protopine 5) which were characterized by spectroscopic methods. Anticholinesterase activities of the extracts and isolated alkaloids were also tested by in vitro Ellman method. The isolated compounds were also analyzed by a molecular docking technique to determine the binding orientations in the gorge of the active site of acetylcholinesterase (AChE) and a homology model of butyrylcholinesterase (BuChE). This is the first comparative investigation of the phytochemical composition and biodiversity of Glaucium flavum species growing in Türkiye.

Defining Requirements for Heme Binding in PGRMC1 and Identifying Key Elements that Influence Protein Dimerization.

Progesterone receptor membrane component 1 (PGRMC1) binds heme via a surface-exposed site and displays some structural resemblance to cytochrome b5 despite their different functions. In the case of PGRMC1, it is the protein interaction with drug-metabolizing cytochrome P450s and the epidermal growth factor receptor that has garnered the most attention. These interactions are thought to result in a compromised ability to metabolize common chemotherapy agents and to enhance cancer cell proliferation. X-ray crystallography and immunoprecipitation data have suggested that heme-mediated PGRMC1 dimers are important for facilitating these interactions. However, more recent studies have called into question the requirement of heme binding for PGRMC1 dimerization. Our study employs spectroscopic and computational methods to probe and define heme binding and its impact on PGRMC1 dimerization. Fluorescence, electron paramagnetic resonance and circular dichroism spectroscopies confirm heme binding to apo-PGRMC1 and were used to demonstrate the stabilizing effect of heme on the wild-type protein. We also utilized variants (C129S and Y113F) to precisely define the contributions of disulfide bonds and direct heme coordination to PGRMC1 dimerization. Understanding the key factors involved in these processes has important implications for downstream protein-protein interactions that may influence the metabolism of chemotherapeutic agents. This work opens avenues for deeper exploration into the physiological significance of the truncated-PGRMC1 model and developing design principles for potential therapeutics to target PGRMC1 dimerization and downstream interactions.

New thiazole, thiophene and 2-pyridone compounds incorporating dimethylaniline moiety: synthesis, cytotoxicity, ADME and molecular docking studies

Various sets of thiazole, thiophene, and 2-pyridone ring structures containing a dimethylaniline component were synthesized. Substituted thiazoles 2–3 and thiophenes 5–7 were produced by reacting thiocarbamoyl compound 4 with α-halogenated reagents in different basic conditions. Also, a series of 2-pyridone derivatives 9a–f substituted with dimethylaniline was synthesized through Michael addition of malononitrile to α,β-unsaturated nitrile derivatives 8a–f. The synthesized products were structurally proven by spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Furthermore, the anti-cancer efficacy of the compounds was assessed using the MTT assay on two cell lines: hepatocellular carcinoma (HepG-2) and breast cancer (MDA-MB-231). The results showed the highest growth inhibition for derivatives 2, 6, 7, and 9c, which were further examined for their IC50 values. The IC50 for compound 2 showed equipotent activity (IC50 = 1.2 µM) against the HepG-2 cell line compared to Doxorubicin (IC50 = 1.1 µM). Compounds 2, 6, 7 and 9c showed very good ADME assessments for further drug administration. Moreover, the PASS theoretical prediction for the compounds showed high antimitotic and antineoplastic activities for compounds 2, 6, 7, and 9c, as well as potent inhibition activity for the insulysin enzyme (IDE). Molecular docking stimulations were performed on CDK1/CyclinB1/CKS2 (PDB ID: 4y72) and BPTI (PDB ID: 2ra3). When docked into (PDB ID: 4y72), all of the tested compounds showed considerable inhibition, and the 2-pyridone derivative 9d had the maximum binding affinity (− 8.1223 kcal/mol). While thiophene derivative 6 offered the maximum binding affinity (− 7.5094 kcal/mol) when docked into (PDB ID: 2ra3).Graphical

Design, Synthesis, Characterization, and Antimicrobial Properties of New Azo Disperse Dyes Incorporating Quinazolinone-Pyrazolone Moieties and Their Applications for Dyeing of Polyester Fabrics

The current study outlines a straightforward and efficient method for creating new quinazolinone disperse dyes based on pyrazolone moieties, starting with quinazolinone and a variety of substituted pyrazolone as couplers. The synthesized dyes were characterized using a variety of spectroscopic and analytical methods. The synthesized dyes' ultraviolet–visible spectra showed bands brought on by several molecular transitions. We investigated in detail the multifunctional characteristics such color representation, dyeing duration, concentration, pH, buildup, and fastness properties of the dyed samples. Fastness properties and colorimetric data showed satisfactory results, demonstrating the effectiveness of these dyes in dyeing polyester fabrics. A pH of 5 and a dyeing temperature of 130 °C were the ideal conditions for dyeing polyester fabrics. Additionally, an ultraviolet protection factor test was performed on the dyed fabrics, and the results showed that these dyes provide the best UV protection. These dyes are suitable for industrial dyeing applications since they are easy to manufacture and scale up. Additionally, in-vitro testing was done to determine the dyes' antibacterial effectiveness against various bacteria and fungi. The antibacterial activity of the dyes was moderate to very good against both Gram-positive and Gram-negative bacteria, as well as fungi.

Bioactive compounds from Withania somnifera dun and their toxicity against some piercing sucking pests

Piercing sucking pests are destructive to many strategic crops all over the world. Botanical pesticides can be used to control these pests. A new withanolide derivative 3 named sominone A ((20R,22R)-1α,3β,20,27-tetrahydroxywitha-5,24-dienolide) was isolated from the alkaloid fraction of the whole plant of Withania somnifera. In addition, there are three known compounds named withasomine 1, methyl isoferulate 2, and coagulin Q 4 were also isolated. The structures of isolated compounds were identified using different spectroscopic methods such as 1D, 2D NMR, and HRESIMS spectroscopy. The alkaloid fraction and the four isolated compounds were tested for their pesticidal activity against four piercing sucking pests (Aphis craccivora Koch, Bemisia tabaci Gennadius, Nezara viridula Linnaeus, and Tetranychus urticae Koch) that attack many strategic crops under laboratory conditions, along with azadirachtin (Okios 3.2% EC) as a positive control. The results showed that the alkaloid compound (withasomine 1) was the most toxic to A. craccivora, B. tabaci, N. viridula, and T. urticae, with LC50 values of 15.44, 36.61, 85.11, and 128.28 ppm, respectively, compared with the control. Withanolide compounds had moderate effects on all tested pests. Biochemical parameters of six enzymes; α-esterase, β-esterase, chitinase, acetylcholinesterase, glutathione-S-transferase, and peroxidase of A. craccivora were estimated at the LC50 value of the most potent compound, withasomine 1 and the values were 38.83, 72.86, 31.45, 506.4, 2.62, and 251.0, respectively. The results demonstrated that all enzymes activity levels were increased compared with the control except a remarkable inhibition in AChE enzyme level was observed compared with control. Therefore, the alkaloid fraction of W. somnifera is a promising extract that contains many active compounds that can be used as a natural pesticide against many harmful pests in agriculture crops.Graphical

Structure, Antioxidant Activity and Antimicrobial Study of Light Lanthanide Complexes with p-Coumaric Acid.

This paper presents the results of a study of the effects of the lanthanide ions Ce3+, Pr3+, Nd3+ and Sm3+ on the electronic structure and antioxidant and biological (antimicrobial and cytotoxic) properties of p-coumaric acid (p-CAH2). Structural studies were conducted via spectroscopic methods (FTIR, ATR, UV). Thermal degradation studies of the complexes were performed. The results are presented in the form of TG, DTG and DSC curves. Antioxidant properties were determined via activity tests against DPPH, ABTS and OH radicals. The reducing ability was tested via CUPRAC assays. Minimum inhibitory concentrations (MICs) of the ligand and lanthanide complexes were determined on E. coli, B. subtilis and C. albicans microorganisms. The antimicrobial activity was also determined using the MTT assay. The results were presented as the relative cell viability of C. albicans, P. aeruginosa, E. coli and S. aureus compared to controls and expressed as percentages. In the obtained complexes in the solid phase, lanthanide ions coordinate three ligands in a bidentate chelating coordination mode through the carboxyl group of the acid. Spectroscopic analysis showed that lanthanide ions increase the aromaticity of the pi electron system of the ligand. Thermal analysis showed that the complexes are hydrated and have a higher thermal stability than the ligand. The products of thermal decomposition of the complexes are lanthanide oxides. In the aqueous phase, the metal combines with the ligand in a 1:1 molar ratio. Antioxidant activity tests showed that the complexes have a similar ability to remove free radicals. ABTS and DPPH tests showed that the complexes have twice the ability to neutralise radicals than the ligand, and a much higher ability to remove the hydroxyl radical. The abilities of the complexes and the free ligand to reduce Cu2+ ions in the CUPRAC test are at a similar level. Lanthanide complexes of p-coumaric acid are characterised by a higher antimicrobial capacity than the free ligand against Escherichia coli bacteria, Bacillus subtilis and Candida albicans fungi.

Investigating the third-order nonlinear optical properties of a Schiff base (DBAP) and its Co/Cu metal complex using Z-scan and DFT methodology

Utilizing UV-visible, Fluorescence spectroscopic, and Z-scan methods, the optical and structural properties of 2-(4-(dimethyl amino)benzylidene amino) phenol (DBAP) and their Co/Cu metal complexes were studied. The Z-scan method has been used to investigate the nonlinear absorption coefficient (β), nonlinear refractive index (n2), third-order susceptibility (χ(3)), and optical limiting (OL). In dimethyl sulfoxide (DMSO) and methanol (MeOH) solvents, the DBAP and their Co/Cu metal complexes display positive nonlinear absorption and a positive nonlinear refractive index, according to the Z-scan data. Using the Z-scan approach and an 800 nm central wavelength, femtosecond amplified 48 fs pulse, 1kHz repetition rate laser, the compound's third-order nonlinear optical (NLO) properties are measured. According to the Z-scan data, we may modify the structure and bonding of legend with metals to improve the NLO capabilities of metal complexes, making this material a promising choice for upcoming optoelectronic and photonic devices. The geometrical structure of the compound is optimized using theoretical computations at the B3LYP that are functional with 6-31G and the LanL2DZ on a mixed basis, as determined by the density functional theory (DFT) framework. They provide insight into the charge transfer interactions taking place in the molecule through their HOMO-LUMO analysis.

Synthesis, Solvatochromic Studies, DFT Calculations, Characterization, and In Silico Molecular Docking Studies of Azo Dyes of 3‐Methyl‐1‐phenyl‐1H‐pyrazol‐5‐amine

AbstractIn this work, the four azo dyes (A1–A4) were synthesized using 5‐amino‐3‐methyl‐1‐phenyl pyrazole with four different coupling components by the conventional, simple diazo‐coupling method. These synthesized azo molecules were confirmed by various spectroscopic methods viz, FT‐IR spectra, HR‐MS spectra, 1H NMR spectra, and 13C NMR spectra. The electronic absorption and fluorescence spectra of synthesized azo compounds were recorded at room temperature, with different solvents. The DFT calculations were performed using 6‐311++G (d, p) basis set to evaluate the global reactive parameters of the synthesized azo dyes. The anti‐microbial activities were studied; the compound A1 exhibited a good antibacterial and anti‐fungal activities. The study of in silico molecular docking of the azo compounds revealed that all the compounds found to possess were extraordinary binding affinity as compared to the standards. The anti‐tuberculosis study was carried against mycobacterium tuberculosis and the results have shown that, the compound A2 showed good sensitivity to the studied azo compounds.

Flowmicro In-Line Analysis-Driven Design of Reactions Mediated by Unstable Intermediates: Flash Monitoring Approach.

The direct observation of reactive intermediates is an important issue for organic synthesis. However, intermediates with an extreme instability are hard to be monitored by common spectroscopic methods such as FTIR. We have developed synthetic method utilizing flow microreactors, which enables a generation and reactions of unstable intermediates. Herein we report that, based on our flowmicro techniques, we developed an in-line analysis method for reactive intermediates in increments of milliseconds. We demonstrated the direct observation of the living and dead species of the anionic polymerization of alkyl methacrylates. The direct information of the living species enabled the anionic polymerization and copolymerization of oligo(ethylene glycol) methyl ether methacrylates, which is the important but difficult reaction in the conventional method.

Five new compounds from the stems of Ephedra equisetina

Five new compounds were identified from the stems of Ephedra equisetina Bunge. Their structures were elucidated by spectroscopic methods, involving UV, IR, NMR spectrum and HRESIMS analyses. The absolute configuration of compound 2 was proved by comparing their experimental and calculated ECD spectrum. The vitro bioactive assay of all compounds suggested that compound 1, 3, 4, 5 and 6 may have potential anti-asthmatic activities.

Flavonoid glycosides from the leaves of Michelia champaca

Michelia champaca L. (Magnoliaceae) was cultivated in large scale for flowers as cosmetic raw materials, whereas the value of its leaves remains to be discovered. Our chemical study on the leaves yielded four new flavonol diglycosides, champaflavosides A–D (1–4), together with twenty-three known flavonoid glycosides (5–27). Their structures were determined by spectroscopic and chemical methods. Compounds 5–21 and 23–27 were not previously reported from the genus Michelia, and kaempferol 3-O-rutinoside (22) was obtained from this species for the first time. All the compounds were evaluated for antioxidant activity by four in vitro assays. Compounds 3–12 and 20 showed more potent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity than l-ascorbic acid (l-AA). Compounds 2–23, 25, and 27 exhibited 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation scavenging activity superior to l-AA. The ferric reducing antioxidant powers (FRAP) of compounds 2–13, 17, and 19 were higher than l-AA. Further, eighteen compounds demonstrated cellular reactive oxygen species (ROS) scavenging activity, of which champaflavoside D (4), rhamnetin 3-O-neohesperidoside (8), quercetin 3-O-(6-O-E-p-coumaroyl)-neohesperidoside (9), and liquiritin (27) were more potent than curcumin. The results revealed that the renewable leaves of M. champaca are a rich source of flavonoids and antioxidants.

Six unprecedented 2-(2-phenethyl)chromone dimers from agarwood of Aquilaria filaria

Six new dimeric 2-(2-phenylethyl)chromones (1–6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1–6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8′′) of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 μM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 μM.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1–3), along with nine known ones (4–12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3–5, and 7 showed a potent neuroprotective effect at 25 or 50 μM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.