Undescribed Compounds Research Articles

Bufadienolides from Helleborus foetidus and their cytotoxic properties on MCF-7 breast cancer cells.

Twelve bufadienolides and six 19-norbufadienolides were isolated from the aerial parts of Helleborus foetidus. They consist of aglycons and glucosides and include nine previously undescribed compounds and a compound reported for the first time as a genuine natural product. Their structures were established by extensive spectroscopic analysis and the structure and absolute configuration of two previously unreported 3,4-epoxy derivatives were confirmed by single crystal X-ray diffraction analysis. The compounds were tested for their cytotoxicity on MCF-7 human breast cancer cells. They show differential cytotoxic activity with IC50 values in the range of 2.4 nM - >10 μM. The potency of the activity strongly correlates with the presence of a C-19 aldehyde group. The data complement the scientific basis underpinning the use of H. foetidus in anthroposophic medicine for the integrative treatment of cancer.

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).

Identification of New Compounds from the Roots of Rubia tibetica Hook. f.

Rubia tibetica Hook. f is a traditional Tibetan medicinal plant, with its roots serving as the primary medicinal part. Two new compounds, Rubiaxylm C and E (1 and 3), and one new natural compound, Rubiaxylm D (2) were isolated from R. tibetica, along with five known compounds (4-8). The structures of the previously undescribed compounds were elucidated by HR-ESIMS, 1D/2D NMR spectroscopic data and electronic circular dichroism calculations. Compound 1 is a rare anthrone substituted with a carbonyl group at position 1. Furthermore, all isolated compounds were tested for their cytotoxicity against HepG2 cell lines.

Biological activities of benzofurans from the fruits of Psoralea corylifolia L. and their mechanism based on network pharmacology and biological verification

Fourteen benzofuran compounds were identified in the fruits of Psoralea corylifolia L., with four previously undescribed compounds (4, 9-11) being discovered. Their chemical structures were definitively determined through comprehensive spectral data analysis. The compounds were investigated for their antioxidant, anti-tumor, and anti-inflammatory properties, revealing that benzofuran compounds exhibit significant anti-inflammatory effects. Compound 2 demonstrated the most potent anti-inflammatory effect, surpassing that of the positive control drug. The potential anti-inflammatory mechanism of 2 was extensively explored through network pharmacology research. Subsequent validation of the selected targets via Western blot analysis confirmed that 2 exerts its anti-inflammatory effects by activating the TLR4/NF-κB pathway. These findings offer a novel perspective on the development of benzofuran glycoside compounds and Psoralea fructus.

Four New Tirucallane Triterpenoids from the Leaves of Ailanthus Triphysa with Anti-Inflammatory Activities.

Isolation and determination of three new compounds from the leaves of Ailanthus triphysa (Dennst.) Alston with their anti-inflammatory activity. Ten tirucallane triterpenes (1-10) including four undescribed compounds, ailantriphysas A-D (1-4), were isolated from the leaves of Ailanthus triphysa (Dennst.) Alston. Their structures were elucidated using IR, HR-ESI-MS, 1D- and 2D-NMR spectra. Compound 1 inhibited lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 cells with an IC50 value of 8.1±μM. Additionally, compound 1 also displayed significant inhibitory effects on the secretion of IL-6 and TNF-α at tested concentrations of 4, 8, and 16 μM.

Phyllanretiosides A and B: Two Undescribed Compounds from Phyllanthus Reticulatus with Nitric Oxide Production Inhibition and Antimicrobial Activity.

Phytochemical study on the methanol extract of the leaves of Phyllanthus reticulatus led to the isolation of two new compounds, phyllanretiosides A (1) and B (2) together with ten known ones (3-12). Their chemical structures were determined by HR-ESI-MS, NMR, and ECD spectra in comparison with the literature. Three ellagitannins, phyllanretioside A (1), corilagin (3), and phyllanthusiin C (4) inhibited lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values of 63.2, 83.2, and 5.6 μM, respectively. In addition, compounds 1, 3, and 4 exhibited significantly antimicrobial activity (MICs: 16-128 μg/mL) towards some of seven microbial strains.

Apocarotenoids from the fresh roots of Rehmannia glutinosa and their anti-pulmonary fibrosis activity

Six undescribed compounds (1–6) and twenty-three known analogues (7–29) were isolated from the fresh roots of Rehmannia glutinosa. The structures of the compounds (1–29) were established through the application of spectroscopic analysis. Compounds 3, 4, 6, 8, 13, 18, 21, 22, 25, and 28 exhibited excellent anti-pulmonary fibrosis activity. The potential mechanistic pathway of 3 was also investigated, whose results indicate that compound 3 ameliorate TGF-β1 induced BEAS-2B cell injury via PI3K/AKT/NF-κB signaling pathway.

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.

Flavaglines with anti-neuroinflammatory activity from Aglaia edulis (Roxb.) Wall. and structure revision of related flavaglines

Eight cyclopenta[b]benzofurans (1, 2, 4, and 5-9) and eight cyclopenta[bc]benzopyrans (3, 10-16), including a revised (4) and three undescribed compounds (1-3), were isolated from the twigs and leaves of Aglaia edulis (Roxb.) Wall. Their structures were determined by a combination of spectral analysis in conjunction with NMR and ECD calculations. Moreover, based on the findings from 13C NMR calculations and DP4+ statistical analysis, an empirical guideline was established to differentiate the structures of cyclopenta[bc]benzopyrans and cyclopenta[b]benzofurans by aggregating chemical shift data from known compounds. This guideline facilitated the proposal of structural revisions for three previously reported analogs (R-1, R-2, R-3). Biological assay indicated that cyclopenta[b]benzofuran flavalines (2, and 4-8) could significantly inhibit NO production in LPS-induced BV-2 cells with IC50 values from 0.002 to 0.05 μM.

Sesquiterpenes from the fruits of Piper longum L. and their anti-inflammatory activity

The fruits of Piper longum are called long pepper, which are well-known culinary spice as well as traditional medicine. In present work, thirteen sesquiterpenes including four undescribed compounds were isolated from P. longum fruits. Compound 1 was a rare methylated bisabolane-type sesquiterpene. Compounds (−)-3 and (+)-3 were a pair of enantiomers of an uncommon humulane which were separated by chiral HPLC. The absolute configurations of compounds 1–3 were confirmed through the means of spectroscopic data analyses, 13C NMR calculations employing DP4+ probability analyses, and ECD calculations. Compounds 2 and 11 presented moderated inhibitory effect on the NO release in LPS-induced RAW264.7 cells with IC50 values of 30.65 ± 0.90 and 38.48 ± 2.42 μM, respectively. Above results enriched the chemical information of P. longum fruits, and meanwhile provided scientific evidences for the anti-inflammatory function of P. longum fruits.

Novel metabolites from the Mariana Trench-derived fungus Talaromyces sp. SY2250

Four previously undescribed compounds talaromyester A (1) and purpuresters C–E (2 – 4), together with known purpurester A (5) and purpuride G (6), were isolated from the metabolites produced by the Mariana Trench sediment-derived fungus Talaromyces sp. SY2250. Compounds 2 – 5, two pairs of racemates, were separated on a chiral HPLC column. Structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses, and optical rotation calculations. Purpuride G (6) showed antiproliferative activity against glioma cells and may be the main active compound responsible for the activity of the crude extract prepared from the culture of Talaromyces sp. SY2250 in rice medium.

Chemical constituents from marine medicinal brown alga-derived Scytalidium lignicola SC228

In this study, a marine medicinal brown alga Sargassum cristaefolium-derived fungal strain Scytalidium lignicola SC228 has been isolated and identified. Column chromatography of the extracts from liquid-fermented products of the fungal strain was carried out, and led to the purification of eight compounds. Their structures were characterized by spectroscopic analysis, and the absolute configurations were further established by single X-ray diffraction analysis and modified Mosher's method as four previously undescribed compounds, namely scytabenzofurans A–C (1–3), and (3S,4S)-5-chloro-3,4-dihydro-4,6,8-trihydroxy-3-methyl-1H-2-benzopyran-1-one (4), along with four known compounds 5–8. All the isolates were subjected to anti-inflammatory and anti-angiogenic assays. Compounds 1–4, 7, and 8 showed moderate nitric oxide production inhibitory activities in lipopolysaccharide-activated BV-2 microglial cells with IC50 in the range of 19.6 ± 0.1 to 49.0 ± 1.2 μM in comparison with that of curcumin (IC50 = 2.7 ± 0.3 μM). Compounds 5–7 exhibited moderate to potent inhibitory effects on EPCs growth with IC50 in the range of 0.5 ± 0.1 to 42.7 ± 0.9 μM as compared to sorafenib (IC50 = 5.50 ± 1.50 μM).

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.

Bioactivity-Guided Isolation of Antistroke Compounds from Gymnadenia conopsea (L.) R. Br.

A bioactivity-guided separation strategy was used to identify novel antistroke compounds from Gymnadenia conopsea (L.) R. Br., a medicinal plant. As a result, 4 undescribed compounds (1-2, 13, and 17) and 13 known compounds, including 1 new natural product (3), were isolated from G. conopsea. The structures of these compounds were elucidated through comprehensive spectroscopic techniques, such as 1D/2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and quantum chemical calculations. An oxygen-glucose deprivation/reoxygenation (OGD/R)-injured rat pheochromocytoma (PC12) cell model was used to evaluate the antistroke effects of the isolates. Compounds 1-2, 10-11, 13-15, and 17 provided varying degrees of protection against OGD/R injury in the PC12 cells at concentrations of 12.5, 25, and 50 µM. Among the tested compounds, compound 17 demonstrated the most potent neuroprotective effect, which was equivalent to that of the positive control drug (edaravone). Then, transcriptomic and bioinformatics analyses were conducted to reveal the regulatory effect of compound 17 on gene expression. In addition, quantitative real-time PCR (qPCR) was performed to verify the results of the transcriptomic and bioinformatics analyses. These results suggest that the in vitro antistroke effect of compound 17 may be associated with the regulation of the Col27a1 gene. Thus, compound 17 is a promising candidate for the development of novel antistroke drugs derived from natural products, and this topic should be further studied.

Steroidal constituents in the whole plants of Helleborus niger and their cytotoxic activity in vitro

Phytochemical investigation of the whole plants of Helleborus niger L. (Ranunculaceae) resulted in the isolation of five undescribed compounds, including one bufadienolide (1), two bufadienolide rhamnosides (2 and 3), and two ecdysteroids (12 and 13), along with eight known compounds (4–11). The chemical structures of 1–3, 12, and 13 were determined by spectroscopic studies, including 2D NMR, and chromatographic and spectroscopic analyses of the hydrolyzed products. Compounds 1–13 were evaluated for their cytotoxic activity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, SBC-3 human small-cell lung cancer cells, and TIG-3 human normal diploid lung cells. Compounds 1–12 showed cytotoxic activity against HL-60, A549, and SBC-3 cells, with IC50 values ranging from 0.0016 to 6.1 μM. Bufadienolide rhamnoside 2 exhibited potent cell proliferation inhibitory activity against SBC-3 cells after 24–48 h of treatment and apoptosis-inducing activity in SBC-3 cells via an intrinsic pathway after 72 h of treatment. The JFCR39 panel screening of 2 suggests that the molecular target of 2 is Na+,K+-ATPase.

Isolation and antifungal activity assessment of natural compounds from the culture medium of actinobacterium Streptomyces sp. BC129-2

Two previously undescribed compounds, including one phenylpropanoid derivative, BC129–2 (1) and one p-menthane analogue, cis-p-menthane-7,8-diol (2), were isolated from the EtOAc-soluble fraction of the culture broth of an actinomycete Streptomyces sp. BC129–2. The structures of all isolates were elucidated on the basis of extensive analyses of spectroscopic data and comparison with literature data. Their antifungal activity was also evaluated. Our results showed that 2 constituents (compounds 1 &2) possessed mild antifungal activity against Fusarium sp. LC8, Neopestalotiopsis sp. BCRC 35002, and Colletotrichum gloeosporioides BCRC 35178. It is worth mentioning that the chemical composition of the type strain Streptomyces sp. BC129–2 has never been studied.

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.

Synthesis of functional derivatives of chlorine-substituted isothiazoles.

Optimal procedures have been developed for the synthesis of substituted isothiazoles containing an active chlorine atom in position 5 of the heterocycle and various functional groups in position 3: carboxyl, hydroxymethyl, aldehyde. Based on these methods, previously undescribed compounds were obtained: 5-morpholino-substituted 3-hydroxymethyl-4- chloroisothiazole, 4-chloroisothiazole-3-carboxylic acid and its methyl ester. The resulting substances are reactive building blocks for organic synthesis of compounds with a high potential for biological activity.

Chemical constituents of five Saxifraga species and their virucidal activities

The chemical constituents of Saxifraga stolonifera, S. fortunei, S. nipponica, S. cortusifolia, and S. rebunshirensis were investigated for structure and virucidal activity. In addition to the Saxifraga species-derived tannins, 30 compounds (1−30) were isolated from the five species. 5-Hydroxy-4-methoxy-3-O-(6-O-caffeoyl)-β-D-glucopyranosyl benzoic acid (1) and kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-β-D-xylopyranoside (2) were identified as undescribed compounds. Although 1 was isolated as the (E)-isomer of its caffeoyl moiety, under light it became over time a mixture of the (Z)-isomer (1a) and (E)-isomer (1). Kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-β-D-glucopyranoside (3) was an analog of 2 and a known compound, whose NMR assignment was reconsidered and described. 6-Isopropyl-5,5-dimethyldihydropyrimidine-2,4(1H,3H)-dione (30) was expected to be a racemic mixture based on its optical rotation and X-ray crystallography data. The virucidal activities of the isolated compounds (1–30) against influenza A virus, severe acute respiratory syndrome coronavirus 2, feline calicivirus, and murine norovirus were evaluated to identify the presence of compounds other than the Saxifraga species-derived tannins, which exhibited virucidal activities. Although the isolated compound activities were relatively weak compared to those of Saxifraga species-derived tannins, the potential virucidal activity of the compounds with galloyl groups was confirmed.

Specialized metabolites of the endophyte Annulohypoxylon areolatum hosted by Aconitum carmichaelii

Seven previously undescribed compounds, including one amino acid hybrid sesquiterpene areolatol A (1), two unusual natural sesquiterpenoid skeleton areolatones A-B (2-3) and four benzo[j]fluoranthene areolaranes A-D (4–7) were characterized from Annulohypoxylon areolatum. The structures of the compounds were determined by extensive spectroscopic analysis, X-ray diffraction analysis, and ECD and NMR computational. Notably, areolatol A (1) was the first reported sesquiterpene featuring a 5/7/3-ring system and hybridized with two molecular amino acids. In addition, areolaranes A-D (4–7) were identified as possible chemophenetic markers.