ECD Data Research Articles

Isolation of Novel Compounds from Lepidium sativum Seeds and Evaluation of Their Potential Anti-Tumor Activity.

Four undescribed compounds including a pair of enantiomers of a dihydroarylnaphthalene lignan [(±)-1], an arylnaphthalene lignan (2), and an indoleacetic acid ester (3), together with four known compounds (4-7), were isolated from the seeds of Lepidium sativum. Their structures were identified by HRMS and NMR spectroscopic data, and the absolute configuration of these compounds were assigned by ECD data in combination with quantum chemical calculations. Compound (-)-1 had weak inhibitory activity against HeLa cell line with an IC50 value of 60.23±3.51 μM, and compound (+)-1 presented moderate inhibitory effect against HeLa cell line with an IC50 value of 19.99±1.00 μM (IC50 value of the positive control was 0.40±0.02 μM).

New Antifungal and Antifeedant Metabolites from Daldinia Eschscholtzii Cocultured with Colletotrichum Pseudomajus.

The synchronous co-culture of Daldinia eschscholtzii and Colletotrichum pseudomajus produced one new linear polyketide, eschscholin C (1), along with three known compounds (2-4). One new acorane sesquiterpene, coldaldrin A (5), and one new amide derivative, coldaldamide A (6) as the probe for polyketide intermediate capture, and three known compounds (7-9) were isolated from the sequential co-culture of D. eschscholtzii with C. pseudomajus. The structures and absolute configurations of 1, 5 and 6 were established by spectroscopic analysis including 1D, 2D NMR, the calculations of the NMR, and ECD data. Most compounds showed significant antifungal activities against the tea pathogens C. pseudomajus, and Fusarium asiaticum with MICs of 2-8 μg/mL. Compound 4 also showed antifeedant activity against silkworms with feeding deterrence indices of 79 % at the concentration of 50 μg/cm2.

New Phthalides and Isochromanone Derivatives from the Deep-Sea-Derived Fungus Penicillium bialowiezense A3.

Two new phthalide derivatives, namely bialowalides A (1) and B (8), and one new isochromanone analogue biourgalide C (11), together with 8 known phthalides (2-7, 9, and 10) as well as two known isochromanones (12 and 13) were discovered from the EtOAc extract of the deep-sea-derived fungus Penicillium bialowiezense A3. The structures were resolved on the basis of extensive spectroscopic analyses (NMR and HRESIMS data), in association with the modified Mosher's method and ECD data for the determination of the absolute configurations. All isolated secondary metabolites (1-13) were tested their antiviral activities against the SARS-CoV-2 trVLP pseudovirus at a concentration of 25 μM. As a result, compounds 1, 5, 11, and 12 exhibited the inhibitory effects against the luminescence at 46.2 %, 39.6 %, 45.5 %, and 48.8 %, respectively.

A new cis‐clerodane‐type furanoditerpenoid from the leaves of Tinospora crispa with inhibitory effect on LPS induced NO production in RAW 264.7 cells

AbstractThree cis‐clerodane‐type furanoditerpenoids (1‐3) including one new compound named tinocrioside D (1) together with four known compounds (4‐7) were isolated from the leaves of Tinospora crispa. Their chemical structures were determined based on the 1D, 2D‐NMR, HR‐ESI‐MS, and ECD data analyses in comparison with the reported data. Compounds 1–3 showed weak inhibition of LPS‐induced NO production in mouse mononuclear macrophages.

Seven undescribed compounds from dried flower buds of Ochrocarpus longifolius

Seven unreported compounds were isolated from dried flower buds of Ochrocarpus longifolius in this study, including an alkaloid ochrocaracid A (1), five coumarins ochrocarpins I (2), J (3), K (4), L (5), and M (6), and one styryl-2-pyranone compound iresinoacid (7) and nine known compounds (8–16). All these compounds were found in O. longifolius for the first time. Their structural elucidation was achieved through NMR, HR-ESI-MS, and ECD data. Additionally, a glucose uptake-promoting activity assay revealed that compounds 10 (128.21 μM) and 16 (123.15 μM) increased the glucose uptake capacity of L6 cells by 1.49-fold and 1.48-fold, respectively. These bioactive compounds could be potential candidates for further pharmaceutical applications.

DMOA-derived polycyclic meroterpenoids with antiviral activities from the deep-sea-derived fungus Penicillium pancosmium A6A

Two undescribed 3,5-dimethylorsellinic acid (DMOA) derived meroterpenoids, namely pancosterpenoids A (1) and B (2), were discovered from the EtOAc extract of the deep-sea sediment-derived fungus Penicillium pancosmium A6A. The gross structures were established by detailed analysis of the spectroscopic data (NMR and HRESIMS spectra), while their absolute configurations were resolved by comparing the experimental and calculated ECD data as well as X-ray single crystal diffraction analysis. Pancosterpenoid A (1) was the first representative of DMOA-derived meroterpenoids possessing a 6/6/6/5/5 pentacyclic system, while pancosterpenoid B (2) belongs to a class of rare 13-nor-citreohybridone meroterpenoids. Two metabolites were evaluated the antiviral effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) trVLP pseudovirus. As a result, compounds 1 and 2 showed moderately inhibitory activities with IC50 values of 22.37 and 18.12 μM, respectively.

A new bicyclo [3.3.1]nonadienemethanol-type lignan from the leaves of Taxus wallichiana Zucc.

Following an α-glucosidase inhibitory activity-guided phytochemical study, a rare new bicyclo[3.3.1]nonadienemethanol-type lignan named 9,9′-oxidolanceolatanin B (1) and four known lignans, lanceolatanin B (2), pinoresinol (3), syringaresinol (4), and medioresinol (5), were isolated from a CHCl3-soluble fraction of Taxus wallichiana Zucc. leaves. The absolute configuration of 9,9′-oxidolanceolatanin B was elucidated based on NMR spectroscopic interpretation and ECD data. All isolated compounds 1–5 showed stronger α-glucosidase inhibitory potency than the positive control, acarbose. This data could support the conceit that Taxus wallichiana leaves could be a promising source for plant-based anti-diabetic drug discovery.

LC–MS coupled with diagnostic ion strategy facilitated the discovery of 5-methylcoumarin meroterpenoids from Gerbera piloselloides

Plant-derived natural products remain crucial in drug development. However, the identification of undescribed natural products is becoming increasingly challenging. A comprehensive strategy combining LC–MS with diagnostic ions was proposed for the discovery of undescribed 5-methylcoumarin meroterpenoids. Thirteen undescribed 5-methylcoumarin meroterpenoids, including five pairs of enantiomers (1a/1b and 5a/5b–8a/8b), were isolated from the whole plant of Gerbera piloselloides. Their structures and absolute configurations were unambiguously determined based on their spectroscopic data, calculated and experimental ECD data and X-ray diffraction analysis. Bioassays conducted on scopolamine-induced injury PC12 cells revealed that compounds 5a/5b, 7a/7b and 8a/8b possessed mild protective effects. Additionally, compounds 2 and 8 showed notable IL-6 inhibition in lipopolysaccharide-induced BEAS-2B cells.

Meroterpenoids with anti-triple negative breast cancer and antimicrobial activities from Arnebia euchroma

Two new meroterpenoids, arneuchrols A and B (1 and 2), together with twelve known analogs (3–14) were isolated from the root of Arnebia euchroma. The structures of 1 and 2 including their absolute configurations were elucidated by NMR, HRESIMS, and DFT calculation of their NMR and ECD data. The structure of pseudoshikonin I, firstly isolated from Lithospermi radix was revised as shikonofuran E (4). Anti-triple negative breast cancer (anti-TNBC) and antimicrobial activities of the isolated compounds were tested. Compounds 3, 4, 6, 7, 9, 10, and 13 exhibited potent inhibitory activity against TNBC (MDA-MB-231 cells) with IC50 values in the range of 0.18–4.58 μM. Compound 10 displayed antifungal activity against five plant pathogenic fungi with MIC values in the range of 6.25–25 μg/mL. Compound 9 exhibited antibacterial activity against Micrococcus lysodeikticus with MIC value of 12.5 μg/mL.

Chemical constituents with their alpha-glucosidase inhibitory activity from the whole plant of Ceratophyllum demersum

From Ceratophyllum demersum growing in Vietnam, twelve compounds were isolated and structurally elucidated, including six previously undescribed compounds, demersones A-D (1-4), acetylvelutins A and B (8 and 9), together with six known compounds, (+)-cyclocolorenone (5), 1-hydroxycyclocolorenone (6), 10-hydroxycyclocolorenone (7), retusin (10), betulinic acid (11), and lupeol (12). The chemical structures and stereochemistry of 1-12 were identified through analysis of spectroscopic data (1D and 2D NMR and HRESIMS), ECD data, and DFT calculation. Notably, this is the first time that humulene-type (1 and 2), guaiane-type (3), and aromadendrane-type sesquiterpenoids (4-7) have been reported in this genus. Compounds 8 and 9 are the first examples of 8-acetoxyflavones found in nature. Upon evaluation of the alpha-glucosidase of 1-3 and 5-12, it was found that 12 exhibited the highest potential with an IC50 value of 15.4 ± 1.1 μM. The molecular docking of 3 and 8 was further studied.

Identification of isoquinoline alkaloids from Corydalis mucronifera and their acetylcholinesterase inhibitory effects

Four new spirobenzylisoquinoline mucroniferanines N − Q (1–4) and a rare chlorinated isoquinoline mucroniferanine R (5) were isolated from Corydalis mucronifera Maxim. Their structures were elucidated based on extensive spectroscopic data analysis of HRESIMS, 1D and 2D NMR, and their absolute configurations were confirmed by ECD data. The isolated compounds were evaluated for acetylcholinesterase (AChE) inhibitory activities. Mucroniferanine R showed significant activities with IC50 values of 0.78 μM compared to galanthamine (1.34 μM). The AChE inhibitory activity was further supported by the molecular docking analysis that exhibited the accommodation of mucroniferanine R in the active site of human AChE.

12-Nor-rotenoids and other cytotoxic constituents of Pachyrhizus erosus seeds

Five previously undescribed compounds, including three 12-nor-rotenoids, were isolated from Pachyrhizus erosus seeds. A brief survey on the dealkylation of selected rotenoids with BBr3 was undertaken. Spectroscopic data of these previously undescribed compounds and reaction products are reported. The proposal of absolute configurations at stereocenters in the isolates and reaction products was based on NMR and ECD data. Most of the isolates and reaction products were evaluated for their growth inhibitory activities against four cancer cell lines and a Vero cell line. Many compounds exhibited strong to moderate activities with IC50 values ranging from 0.06 to 20.9 μM, and their structure-activity relationships were evaluated.

Antimicrobial Dihydroflavonols and Isoflavans Isolated from the Root Bark of Dalbergia gloveri.

Three new dihydroflavonols, gloverinols A-C (1-3), a new flavon-3-ol, gloverinol D (4), two new isoflavans, gloveriflavan A (5) and B (6), and seven known compounds were isolated from the root bark of Dalbergia gloveri. The structures of the isolates were elucidated by using NMR, ECD, and HRESIMS data analyses. Among the isolated compounds, gloverinol B (2), gloveriflavan B (6), and 1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4-hydroxyphenyl)-1-propanone (10) were the most active against Staphylococcus aureus, with MIC values of 9.2, 18.4, and 14.2 μM, respectively.

Millmerranones G, a meroterpene isolated from a mangrove-derived fungus Aspergillus sp. GXIMD 03004

One new meroterpene derivative, millmerranones G (1), and three known analogues (2–4) were identified from the mangrove-derived fungus Aspergillus sp. GXIMD 03004, which was isolated from the leaves of mangrove Acanthus ilicifolius L. collected from Beibu Gulf in China. The structure of 1 was characterised by a comprehensive interpretation of the NMR spectroscopic and HRESIMS data. The absolute configuration for 1 was established using experimental and calculated ECD data. The anti-Vibrio activities of all compounds were evaluated, the result showed that compounds 1 and 2 has weak activity against Vibrio harveyi.

New sesquineolignan glycoside isomers from the aerial parts of Leonurus japonicus and their absolute configurations

The acid water-soluble fraction of the 95% EtOH extract of Leonurus japonicus exhibited significant anti-inflammatory activity by suppressing the p-ERK/ERK ratio and iNOS expression. A further phytochemical investigation of this acid water-soluble fraction led to the isolation of three previously undescribed sesquineolignan glycosides, leolignosides A–C (1–3), and their planar structures were elucidated using HR-ESI-MS and 1D and 2D NMR. To determine the complicated absolute configuration of sesquineolignan glycosides, coupling constants, NOESY data, empirical rules, enzymatic hydrolysis, and ECD data were comprehensively used. These isolated compounds were also screened for anti-inflammatory activity. Encouragingly, leolignosides A–C all suppressed LPS-induced NO overproduction in RAW 264.7 macrophages. The aglycone (3a) of leolignoside C was chosen for further investigation for its activity and the available amount. Similar to the acid water-soluble fraction, compound 3a inhibited NO overproduction and decreased the p-ERK/ERK and p-NF-κB/NF-κB ratios, indicating that 3a may exert anti-inflammatory effects through the ERK/NF-κB signaling pathway.

Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.

Bioactive Naphthoquinone and Phenazine Analogs from the Endophytic Streptomyces sp. PH9030 as α-Glucosidase Inhibitors.

A talented endophytic Streptomyces sp. PH9030 is derived from the medicinal plant Kadsura coccinea (Lem.) A.C. Smith. The undescribed naphthoquinone naphthgeranine G (5) and seven previously identified compounds, 6-12, were obtained from Streptomyces sp. PH9030. The structure of 5 was identified by comprehensive examination of its HRESIMS, 1D NMR, 2D NMR and ECD data. The inhibitory activities of all the compounds toward α-glucosidase and their antibacterial properties were investigated. The α-glucosidase inhibitory activities of 5, 6, 7 and 9 were reported for the first time, with IC50 values ranging from 66.4 ± 6.7 to 185.9 ± 0.2 μM, as compared with acarbose (IC50 = 671.5 ± 0.2 μM). The molecular docking and molecular dynamics analysis of 5 with α-glucosidase further indicated that it may have a good binding ability with α-glucosidase. Both 9 and 12 exhibited moderate antibacterial activity against methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentration (MIC) values of 16 μg/mL. These results indicate that 5, together with the naphthoquinone scaffold, has the potential to be further developed as a possible inhibitor of α-glucosidase.

Intriguing steroid glycosides for cancer therapy by suppressing the DNA damage response and mTOR/S6K signaling pathways

Two rare 8-hydroxysteroid glycosides (6–7), and their downstream metabolites (1–5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8–14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1–14 on liver and lung cancer cell lines were evaluated, and preliminary structure–activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways.

Monoterpene-chalcone conjugates and diarylheptanoids isolated from the seeds of Alpinia katsumadai Hayata with cytotoxic activity

Five undescribed monoterpene-chalcone conjugates (1-5), one undescribed hypothetical precursor of diarylheptanoid (6), two undescribed diarylheptanoids (7–8), and fourteen known compounds (9–22) were isolated from the seeds of Alpinia katsumadai. Their structures were elucidated through the interpretation of HRESIMS, NMR, ECD, and X-ray diffraction data. MTT assays on human cancer cell lines (HepG2, A549, SGC7901, and SW480) revealed that compounds 3–8, 11, and 13 exhibited broad-spectrum antiproliferative activities with IC50 values ranging from 3.59 to 21.78 μM. B cell lymphoma 2 was predicted as the target of sumadain C (11) by network pharmacology and verified by homogeneous time-resolved fluorescence assay and molecular docking.

Anti-inflammatory lindenane sesquiterpenoid dimers from the roots of Chloranthus holostegius var. trichoneurus.

Two new lindenane-type sesquiterpenoid dimers, chlotrichenes C and D (1 and 2) together with five known lindenane-type sesquiterpenoid dimers (3-7) were isolated from the roots of Chloranthus holostegius var. trichoneurus, a famous natural medicine named as "Sikuaiwa" for subduing swellings and relieving pain. The structures including absolute configuration were elucidated by their 1D and 2D NMR, HRESIMS, and ECD data. Compounds 1 and 2 were classical [4 + 2] lindenane-type sesquiterpenoid dimers that differed from known analogs in oxidation profile, side chain profile, and double bond position. The new isolates and compound 3 exhibited significant inhibitory activity on IL-1β production (IC50: 1-15μM) in LPS-induced THP-1 cells and other compounds exhibited inhibitory activity on NO production in LPS-induced RAW 264.7 cells (IC50: 24-33μM).