Aromatic glycosides and lignans glycosides with their acetylcholinesterase inhibitory activities from the leaves of Picrasma quassioides.

In this study, eight new natural products were isolated from the leaves of Picrasma quassioides. Spectroscopic techniques were used for the elucidation of their planar structures. Their absolute configurations were elucidated on the basis of electron circular dichroism (ECD) techniques combined with the P/M helicity rule for the 2,3-dihydrobenzofuran chromophore, and saccharide hydrolysis. Cholinesterase inhibitors are often used as Alzheimer's disease inhibitors.Thus, acetylcholinesterase and butyrylcholinesterase inhibitory activity of these eight compounds were tested, and results showed that only compound 6 showed weakly acetylcholinesterase inhibitory activity. In particular, molecular docking was used to illustrate the bindings between compound 6 and the active sites of AChE.

Sesquiterpenes from Chloranthus holostegius with anti-inflammatory activities.

The phytoconstituents of the whole plants of Chloranthus holostegius were investigated. As a result, thirteen undescribed sesquiterpenes (chloranholosins A-M, 1-13), including ten acorane-type sesquiterpenes (1-10), one germacrene-type sesquiterpene (11), and two lindenane-type sesquiterpenes (12-13), together with fifteen known sesquiterpenes were isolated. Their structures and absolute configurations were elucidated by a comprehensive method including the spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction. Chloranholosin L (12) was elucidated as a rare lindenane-type sesquiterpene featuring 14α-Me and 5-OH moieties. And chloranholosin M (13) was the first lindenane-type sesquiterpene possessing ß-cyclopropane, 14α-Me, and 5ß-H configuration from the family Chloranthaceae. Furthermore, twelve new isolates and some known sesquiterpenes were evaluated for their inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophage cells. Among them, compounds 12, 16, and 23 showed comparable inhibitory activity to that of the positive control, with IC50 values of 47.9, 41.5, and 48.3 µM, respectively.

Limonoids and alkaloids from Tetradium austrosinense (Hand.-Mazz.) T.G.Hartley.

A pair of new enantiomeric indolopyridoquinazoline-type alkaloids, (+)-1,7S,8R- and (-)-1,7R,8S-trihydroxyrutaecarpine (3a and 3b), and a new limonoid-tyrosamine hybrid, austrosinin (8), along with six known alkaloids and limonoids, were isolated from the stems with leaves of Tetradium austrosinense. Their structures were elucidated on the basis of analysis of MS, NMR, ECD and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations, as well as proposed biosynthetic pathway. An anti-inflammatory bioassay in vitro showed 8 had significant immunosuppressive effect against the production of pro-inflammatory cytokine TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Discovery of bioactive polycyclic polyprenylated acylphloroglucinols with adamantine/homoadamantane skeletons from Hypericum wilsonii.

In this work, nine previous undescribed polycyclic polyprenylated acylphloroglucinols with adamantine/homoadamantane skeletons, cumilcinols A-I (1-9), along with six known analogues, were isolated and identified from the stems, leaves and flowers of Hypericum wilsonii. Their structures were determined by HRESIMS, NMR spectroscopic analysis, single-crystal X-ray crystallography as well as electronic circular dichroism calculations and comparisons. Compound 2 formed a unique furan ring bearing a rare acetal functionality. In bioassays, hyperacmosin G (13) could significantly inhibit the production of NO in LPS-stimulated RAW264.7 cell (IC50 = 4.350 ± 1.146 µM), and increased expression of related transcription factors at the gene level, inhibit the nuclear translocation of NF-κBp65, and reduce the protein expression of COX-2. Additionally, compound 5 showed significant inhibitory activity on Con A-induced T-lymphocyte proliferation (IC50 = 4.803 ± 3.149 µM), and treatment of 5 could reduce the increased ratio of CD4 and CD8 subpopulations induced by Con A in vitro. Those results indicated 13 possesses potential anti-inflammatory activity, and 5 exhibits a certain degree of immunosuppressive activity.

Fungal polyketides produced by an endophytic fungus Phoma sp. associated with Gastrodia elata.

Two novel fungal polyketides, phometides A (1) and B (2), together with four known compounds (3-6), were isolated from the endophytic fungus Phoma sp. YUD17001 obtained from Gastrodia elata Blume. The structures were elucidated based on spectroscopic analyses, X-ray crystal diffraction, and time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Structurally, phometide A (1) represented the first example of C12 polyketide characterized by an unusual tetrahydrobenzofuran-3(2H)-one core with an α,ß-unsaturated ketone functionality, while phometide B (2) was an unprecedented molecule containing a 2-pentylcycloheptan-1-one scaffold. In an antimicrobial activity assay, phometide A (1) exhibited significant inhibitory activity against Staphylococcus aureus with MIC value of 4 µg/mL. Phometide B (2) showed moderate antifungal activity against Candida albicans with an MIC value of 16 µg/mL. Furthermore, compounds 1 and 2 were evaluated for their acetylcholinesterase inhibitory and cytotoxic activities.

Alkaloids from Corydalis saxicola and their antiproliferative activity against cancer cells.

Eight undescribed alkaloids named corydalisine D-K (1-7), including one isoquinoline benzopyranone alkaloid (1), one benzocyclopentanone alkaloid (2), four benzofuranone alkaloids (3, 4, and 5a/5b) and two protoberberine alkaloids (6 and 7), along with fourteen known ones, were isolated from the Corydalis saxicola. Their structures, including absolute configurations, were unambiguously identified using spectroscopic techniques, single-crystal X-ray diffraction and electron circular dichroism calculation. Compounds 2, 14 and 21 exhibit antiproliferative activity against five cancer cell lines. The aporphine alkaloid demethylsonodione (compound 14), which exhibited the best activity (IC50 = 3.68 ± 0.25 µM), was subjected to further investigation to determine its mechanism of action against the T24 cell line. The molecular mechanism was related to the arrest of cell cycle S-phase, inhibition of CDK2 expression, accumulation of reactive oxygen species (ROS), induction of cell apoptosis, inhibition of cell migration, and activation of p38 MAPK signaling pathway. The results indicated that 14 could be used as a potential candidate agent for further development of anti-bladder transitional cell carcinoma.

Abietane diterpenoids and iridoids from Caryopteris mongolica.

Six new abietane diterpenoids (1-6) and five undescribed iridoids (7-11) have been isolated from the aerial parts of Caryopteris mongolica. The intricate structural characterization of these compounds was meticulously undertaken using an array of advanced spectroscopic techniques. This process was further enhanced by the application of DP4+ probability analyses and electronic circular dichroism (ECD) calculations. Following isolation and structural elucidation, the cytotoxicity of these compounds was evaluated. Among them, compound 3 stood out, displaying significant cytotoxic activity against HeLa cells with an IC50 value of 7.83 ± 1.28 µmol·L-1. Additionally, compounds 1, 2, 4, 9, and 10 manifested moderate cytotoxic effects on specific cell lines, with IC50 values ranging from 11.7 to 20.9 µmol·L-1.

Terpenoids from the endophytic fungus Microdiplodia sp. and their anti-inflammatory activities.

Motivated by the potential anti-inflammatory effect of the crude extract of endophytic fungus Microdiplodia sp. CJ01 derived from Camellia sinensis, chemical investigation of the extract of Microdiplodia sp. CJ01 led to the isolation and identification of sixteen terpenoids, including five undescribed eremophilane sesquiterpenoids named microdiplodins A-E (1-5), one undescribed meroterpenoid 13-carboxymacrophorin A (13), seven known eremophilane sesquiterpenoids (6-12), and three known meroterpenoids (14-16). The structures of these compounds were elucidated based on extensive spectroscopic analysis, including nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) data. Their absolute configurations were determined by calculational and experimental electronic circular dichroism (ECD) data. Anti-inflammatory activity assays revealed that compounds 3, 4, 14-16 exhibited moderate inhibitory effects on the production of nitric oxide (NO) in the lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells.

2,3-Seco and 3-nor guaianolides fromAchillea alpina with antidiabetic activity.

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1ß, which was achieved through the suppression of the NLRP3 pathway.

Neurotrophic neolignans of Pinus koraiensis twigs.

Four undescribed neolignan analogs, together with eight known compounds, were isolated from the twigs of Pinus koraiensis (Korean pine). The chemical structure of the isolated compounds was determined through extensive spectroscopic analysis and chemical method. Their relative and absolute configurations were assigned through a well-established empirical rule and electronic circular dichroism (ECD) analysis, respectively. Four compounds (3 and 9-11) at 20 µM concentration showed significant neurotrophic effect by inducing nerve growth factor (NGF) secretion in C6 cells with the stimulation levels a range of 140.82 ± 4.62% to 160.04 ± 11.04%. Additionally, the result indicated that the glycosylation of neolignan led to an improvement in neurotrophic activity compared to their aglycone form. A compound (7) inhibited nitric oxide production with an IC50 value of 31.74 µM in LPS-activated BV2 cells.

Diverse prenylated C6-C3 derivatives from the stems and branches of Illicium ternstroemioides A. C. Smith with anti-inflammatory and antiviral activities.

Fifteen unreported prenylated C6-C3 derivatives (1-15) were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith, including one bis-prenylated C6-C3 derivative (1), three prenylated C6-C3 derivative-shikimic acid ester hybrids (2-4) and 11 prenylated C6-C3 monomers (5-15). The structures of compounds 1-15 were elucidated by spectroscopic analysis (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of the compounds were determined using electronic circular dichroism (ECD), induced circular dichroism (ICD), and the modified Mosher's method. Among the isolates, compounds 11, 12, and 15 exhibited significant anti-inflammatory activities by inhibiting the nitric oxide with IC50 values ranging from 1.89 to 24.83 µM in lipopolysaccharide-stimulated murine RAW 264.7 macrophages and murine BV2 microglial cells; compounds 2, 3, and 7 exhibited antiviral activitives against Coxsackievirus B3 with an IC50 value of 33.3, 25.9, and 27.8 µM, respectively.

Exploring the cytotoxicity on human lung cancer cells and DNA binding stratagem of camptothecin functionalised silver nanoparticles through multi-spectroscopic, and calorimetric approach.

The influence of nanoparticles inside the human body and their interactions with biological macromolecules need to be explored/studied prior to specific applications. The objective of this study is to find the potential of camptothecin functionalised silver nanoparticles (CMT-AgNPs) in biomedical applications. This article primarily investigates the binding stratagem of CMT-AgNPs with calf thymus DNA (ctDNA) through a series of spectroscopic and calorimetric methods and then analyses the anticancer activity and cytotoxicity of CMT-AgNPs. The nanoparticles were synthesized using a simple one pot method and characterized using UV-Visible, fourier transform infrared (FTIR) spectroscopy, X-ray diffraction and high-resolution transmission electron microscopy (HRTEM). The average size of CMT-AgNPs is 10 ± 2 nm. A group of experimental techniques such as UV-Visible spectrophotometry, fluorescence dye displacement assay, circular dichroism (CD) and viscosity analysis unravelled the typical groove binding mode of CMT-AgNPs with ctDNA. The CD measurement evidenced the minor conformational alterations of double helical structure of ctDNA in the presence of CMT-AgNPs. The information deduced from the isothermal titration calorimetry (ITC) experiment is that the binding was exothermic and spontaneous in nature. Moreover, all the thermodynamic binding parameters were extracted from the ITC data. The binding constants obtained from UV absorption experiments, fluorescence dye displacement studies and ITC were consistently in the order of 104 Mol-1. All these results validated the formation of CMT-AgNPs-ctDNA complex and the results unambiguously confirm the typical groove binding mode of CMT-AgNPs. An exhaustive in vitro MTT assay by CMT-AgNPs and CMT against A549, HT29, HeLa and L929 cell lines revealed the capability of CMT-AgNPs as a potential anticancer agent.

Iridoids and derivatives from Catalpa ovata with their antioxidant activities.

Six new iridoid derivatives (1-6)，together with twelve known compounds (7-18), were isolated and identified from the dried fruits of Catalpa ovata G. Don. Their chemical structures were mainly established through the relative spectroscopic data, while the absolute configurations of compounds 2 and 3 were elucidated on the electronic circular dichroism calculations. Their antioxidant activities were evaluated by activating the Nrf2 transcriptional pathway in 293 T cells in vitro. Among them, Compounds 1, 3, 4, 6-8, 10-12, 14, 15, 17 and 18 showed significant Nrf2 agonistic effect compared with the control group at 25 µM. Finally, The hypothetical biosynthetic pathway for 1-13 was discussed.

Circular dichroism assessment of an imidazole antifungal drug with plant based silver nanoparticles: Quantitative and DFT analysis.

Circular dichroism (CD) methods have been developed for the analysis of luliconazole (LUC) using plant based silver nanoparticles (P-AgNPs). Cleaner and natural approach have found significant attention in recent times owing to their exceptional physicochemical characteristics. Utilizing FTIR, SEM, and XRD, the produced nanoparticles were analyzed. The produced P-AgNPs were then used to assay LUC in formulation drugs. Four CD methods are developed as zero order and second order derivative methods. Methods I and II are based on a normal CD scan (zero order) that produced calibration range from 2 - 16 µgmL-1 at 232 nm (positive band) and 299 nm (negative band), respectively. Methods III and IV are the second order derivative methods that are developed at 232 nm (negative band) and at 251 nm (positive band). Density functional theory study was done to comprehend the feasibility of the developed methods and to optimize the structure and energy gap that validated the experimental procedure. The LUC assay methods using the proposed CD approach are simple, sensitive and precise with a limit of detection for methods I, II, III and IV of 0.527, 0.428, 0.250 and 0.30 µgmL-1 and limit of quantification of 1.75, 1.42, 0.833 and 1.0 µgmL-1, respectively. For intra- and inter-day precision, the recovery data ranged from 99.48 to 101% and 99.37 to 101%, respectively. The methods were used in dosage forms that produced a relative standard deviation of less than 2% and the true bias (θL and θU) within ±2%, demonstrating the potential use of the developed methods.

Derivatives of sesquiterpenes, 2-furaldehyde, phenols, and alkaloids isolated from Taraxacum mongolicum.

Four new compounds (1-4), together with 23 known compounds (5-27), were isolated from the whole plant of Taraxacum mongolicum. Among them, one racemic mixture (4) was separated with a chiral HPLC column. Their structures were identified by spectroscopic evidence and mass spectrometry. The absolute configurations of compounds 1, 3, and 4 were determined via comparison of their calculated and experimental electronic circular dichroism (ECD) spectra. Compound 3 showed an inhibitory effect against aldose reductase with a 59.1% inhibition. Two known compounds (13 and 27) showed α-glucosidase inhibition of 51.5% and 56.0%, respectively.

Seven new meroterpenoids from the fungus Penicillium sclerotiorum GZU-XW03-2.

Seven previously undescribed meroterpenoids, peniscmeroterpenoids H - N (1-7), were isolated from the marine-derived fungus Penicillium sclerotiorum GZU-XW03-2. Their structures were established by the spectroscopic methods and the electronic circular dichroism (ECD) calculations. Peniscmeroterpenoid H was a 6/6/6/5/6 rearranged pentacyclic meroterpenoid, featuring a unique 2-oxaspiro[5.5] undeca-4,7-dien-3-one motif. Peniscmeroterpenoids I and J (2 and 3) owned rare 6(D)/5(E) fused rings were not common in natural products, and compound 2 was the second example of a berkeleyone analogue stripped of the methyl ester fragment. Peniscmeroterpenoid K (4) was the first case where the C-24 was oxidized. In bioassay, compound 5 showed moderate anti-inflammatory activity.

Selenium-Substituted Monomethine Cyanine Dyes as Selective G-Quadruplex Spectroscopic Probes with Theranostic Potential.

The binding interactions of six ligands, neutral and monocationic asymmetric monomethine cyanine dyes comprising benzoselenazolyl moiety with duplex DNA and RNA and G-quadruplex structures were evaluated using fluorescence, UV/Vis (thermal melting) and circular dichroism (CD) spectroscopy. The main objective was to assess the impact of different substituents (methyl vs. sulfopropyl vs. thiopropyl/thioethyl) on the nitrogen atom of the benzothiazolyl chromophore on various nucleic acid structures. The monomethine cyanine dyes with methyl substituents showed a 100-fold selectivity for G-quadruplex versus duplex DNA. Study results indicate that cyanines bind with G-quadruplex via end π-π stacking interactions and possible additional interactions with nucleobases/phosphate backbone of grooves or loop bases. Cyanine with thioethyl substituent distinguishes duplex DNA and RNA and G-quadruplex structures by distinctly varying ICD signals. Furthermore, cell viability assay reveals the submicromolar activity of cyanines with methyl substituents against all tested human cancer cell lines. Confocal microscopy analysis shows preferential accumulation of cyanines with sulfopropyl and thioethyl substituents in mitochondria and indicates localization of cyanines with methyl in nucleus, particularly nucleolus. This confirms the potential of examined cyanines as theranostic agents, possessing both fluorescent properties and cell viability inhibitory effect.

Investigation of the interactions of HSA and SARS-CoV-2 papain-like protease against eugenol for novel COVID-19 drug discovery: spectroscopic and insilico study.

Coronavirus family consist of a member known as SARS-CoV-2, spread drastically in 2019 (Covid-19), affecting millions of people worldwide. Till date there is no clear-clinical therapy or drug, targeted to cure this serious disease. Researches are going on to prevent this corona virus. Here, we tried to explore a novel SARS-CoV-2 papain-like protease as a potential inhibitor. Finally, eugenol was docked with this protease to find prime SARS-inhibitors. In silico studies revealed that eugenol binds to the active site of SARS-CoV-2 papain-like protease with appropriate binding. Moreover, the MD simulation for 100 ns and MMPBSA calculation reveals that eugenol possess potential phytotherapeutic properties against COVID-19. The interaction of eugenol with human serum albumin has been examined by using fluorescence, UV-vis spectroscopy, circular dichroism as well as computational techniques such as molecular docking, molecular dynamic simulation and MMPBSA calculation. Overall investigation shows eugenol having good affinity for HSA Ka 6.80 × 106 M-1.Communicated by Ramaswamy H. Sarma.

Preparation and identification of isoquinoline alkaloids with ATP citrate lyase inhibitory activity from Dactylicapnos scandens.

Three new isoquinoline alkaloids including a morphine derivative (1), two aporphine alkaloids (2-3), together with five known alkaloids (4-8) were obtained from the extract of Dactylicapnos scandens (D.Don) Hutch. (D. scandens). Their structures and absolute configurations were elucidated by extensive spectroscopic data analysis including HRESIMS, NMR and electronic circular dichroism (ECD) and ECD calculation. Compounds 1-8 were evaluated for ATP Citrate Lyase (ACLY) inhibitory activity through an enzymatic assay. Among them, 2 and 3 showed the high ACLY inhibitory activity with an IC50 value of 10.48 ± 1.59 and 10.89 ± 4.89 µM.

Hyperhubeins A-I, Bioactive Sesquiterpenes with Diverse Skeletons from Hypericum hubeiense.

Nine new sesquiterpenes, hyperhubeins A-I (1-9), and 14 known analogues (10-23) were isolated from the aerial portions of Hypericum hubeiense. Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-3 possess an unprecedented sesquiterpene carbon skeleton. Further, a plausible biosynthetic pathway from farnesyl diphosphate (FPP) is proposed. The isolated phytochemicals were evaluated for neuroprotective and anti-neuroinflammatory properties in vitro. Compounds 1, 2, 5-8, 14, and 21 displayed notable neuroprotective activity against hydrogen peroxide (H2O2)-induced lesions in PC-12 cells at 10 µM. Additionally, compounds 1, 2, 12, and 13 exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC50 values ranging from 4.92 to 6.81 µM. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound 12 exerted anti-neuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF-κB) signaling.