Lactones from the pericarps of Litsea japonica and their anti-inflammatory activities

Five new lactones, litsenolide F₁ (1), lisealactone H₁ (10), lisealactone H₂ (11), akolactone D (13), and akolactone E (14), along with thirteen known compounds were isolated from the pericarps of Litsea japonica (Thunb.) Jussieu. Their chemical structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, HRMS, and chemical methods. The isolated compounds were evaluated for their inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among them, 2-alkylidene-3-hydroxy-4-methylbutanolide derivatives (compounds 1–9) exhibited the most potent activity, with IC₅₀ values in the range of 2.9–12.8?μM. In additon, compounds 1, 3, 4, and 6 showed inhibition of iNOS and COX-2 expression in concentration-dependent manner. Compound 3 suppresses mRNA expression of iNOS, COX-2, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells. Based on these evidence, the isolated lactones from L. japonica could be promissing candidates for the development of new anti-inflammatory agents.     

Caged xanthones displaying protein tyrosine phosphatase 1B (PTP1B) inhibition from Cratoxylum cochinchinense

Four new caged xanthones (1–4) and two known compounds (5, 6) were isolated from the roots of Cratoxylum cochinchinense, a polyphenol rich plant, collected in China. The structures of the isolated compounds (1–6) were characterized by obtaining their detailed spectroscopic data. In particular, compounds 1 and 6 were fully identified by X-ray crystallographic data. The isolated compounds (1–6) were evaluated against protein tyrosine phosphatase 1B (PTP1B), which plays an important role in diabetes, obesity, and cancer. Among these compounds, 3, 4, and 6 displayed significant inhibition with IC₅₀ values of 76.3, 43.2, and 6.6 µM, respectively. A detailed kinetic study was conducted by determining K_m, V_max, and the ratio of K_ik and K_iv, which revealed that all the compounds behaved as competitive inhibitors.     

Chemical constituents from Baphia leptobotrys Harms (Fabaceae) and their chemophenetic significance

The chemical investigation of the CH₂Cl₂/MeOH (1:1) extract of the trunk bark and leaves of Baphia leptobotrys Harms (Fabaceae) led to the isolation of nineteen compounds (1–19). Their structures were elucidated based on the analysis of their NMR and MS data. Except for compounds 3–5, 14 and 15, all the isolated compounds are reported from the genus Baphia for the first time. Furthermore, compounds 8, 10, 16, 17 are isolated from the Fabaceae family for the first time. The crude extract and isolated compounds were screened in vitro for their antileishmanial activity against Leishmania donovani 1S (MHOM/SD/62/1S) promastigotes and cytotoxicity towards Raw 264.7 macrophage cells. The crude extract of B. leptobotrys exhibited moderate activity (IC₅₀ = 63.40 μg/mL). Amongst the tested compounds, ergosterol peroxide (9) and germanicol caffeoyl ester (8) exhibited good activity with IC₅₀ values of 9.43 and 10.24 μM, respectively and showed acceptable selectivity towards macrophage cells (SI > 3.85). The chemophenetic significance of these compounds is also discussed.     

Three new cucurbitane triterpenoids from Hemsleya penxianensis and their cytotoxic activities

Two new cucurbitane glycosides, hemslepenside A (1) and 16,25-O-diacetyl-cucurbitacin F-2-O-β-d-glucopyranoside (3), one new cucurbitacin, 16-O-acetyl-cucurbitacin F (2), along with three known cucurbitane compounds, were isolated from the roots of Hemsleya penxianensis. The structures of 1–6 were established on the basis of extensive spectroscopic and chemical methods. The isolated compounds were evaluated for their cytotoxic activities against different three human cancer cell lines, with IC₅₀ values in the low microgram range.     

Bioactive monoterpene indole alkaloids from Nauclea officinalis

Two new monoterpene indole alkaloids, naucleaoffines A (1) and B (2), together with six known alkaloids (3–8), were isolated from the stems and leaves of Nauclea officinalis. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. All isolated compounds were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1–8 exhibited significant inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC₅₀ values comparable to that of hydrocortisone. In addition, compounds 1–8 showed significant anti-HIV-1 activities with EC₅₀ ranged from 0.06 to 2.08 µM. These findings suggest that the discoveries of these indole alkaloids with significant anti-inflammatory activities and anti-HIV-1 activities isolated from N. officinalis could be of great importance to the development of new anti-inflammatory and anti-HIV agents.     

Cytotoxic azaphilone alkaloids from Chaetomium globosum TY1

Three novel azaphilone alkaloids, namely chaetomugilides A–C (1–3), together with three related compounds (4–6) were isolated from the methanol extract of Chaetomium globosum TY1, an endophytic fungus isolated from Ginkgo biloba. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis. The isolated compounds exhibited highly cytotoxic activities against human cancer cell line HePG2 with the IC₅₀ values range from 1.7 to 53.4 μM.     

Xylarianins A-D from the endophytic fungus Xylaria sp. SYPF 8246 as natural inhibitors of human carboxylesterase 2

Eighteen secondary metabolites were isolated from the fermentation broth of the endophytic fungus Xylaria sp. SYPF 8246, including four new compounds, xylarianins A-D (1–4), three new natural products, 6-methoxycarbonyl-2′-methyl-3,5,4′,6′-tetramethoxy-diphenyl ether (5), 2-chlor-6-methoxycarbonyl-2′-rnethyl-3,5,4′,6′-tetramethoxy-diphenyl ether (6), and 2-chlor-4′-hydroxy-6-methoxy carbonyl-2′-methyl-3,5,6′-trimethoxy-diphenyl ether (7), and eleven known compounds (8–18). Their structural elucidations were conducted by using 1D and 2D NMR, HRESIMS, and Rh₂(OCOCF₃)₄-induced electronic circular dichroism (ECD) spectra analyses. The integrated ¹H and ¹³C NMR data of three new natural products 5–7 were reported for the first time. All the isolated compounds were assayed for their inhibitory activities against human carboxylesterase 2 (hCE 2). Compounds 1, 5–9, and 18 displayed significant inhibitory activities against hCE 2 with IC₅₀ values of 10.43 ± 0.51, 6.69 ± 0.85, 12.36 ± 1.27, 18.25 ± 1.78, 29.78 ± 0.48, 18.86 ± 1.87, and 20.72 ± 1.51 µM, respectively. The interactions between compounds 1 and 5 with hCE 2 were anaylzed by molecular docking.     

Inhibitory constituents of the heartwood of Dalbergia odorifera on nitric oxide production in RAW 264.7 macrophages

Two new isoflavanones (1 and 13), along with 25 known compounds (2–12, 14–27), were isolated from the EtOAc-soluble fraction of the heartwood of Dalbergia odorifera by following their potential to inhibit the LPS-induced nitric oxide production in RAW 264.7 cells. The structures of the isolated compounds were established by spectroscopic data such as ¹D, ²D NMR and MS spectrometry. Among the isolated compounds, (2S)-pinocembrin (26), showed the most potent inhibitory effect with IC₅₀ value of 18.1 μM.     

Cytotoxic metabolites from the leaves of the mangrove Rhizophora apiculata

One new 8,4’-oxyneolignan (1) and one new 7,8-dihydrobenzofuranone (2), together with twenty-one known compounds (3‒23) were isolated from the methanol extract of Rhizophora apiculata leaves. The structures of new compounds, as well as their absolute configuration, were determined by a combination of spectroscopic methods and quantum chemical calculations of NMR and ECD data. All isolated compounds were evaluated for their cytotoxicity, and only 2,6-dimethoxy-1,4-benzoquinone (8) exhibited inhibitory effects against SK-LU-1, HepG2, and MCF7 cells with IC₅₀ values in the range of 8.33–14.82 μM.     

Isolation,structural elucidation,and insights into the anti-inflammatory effects of triterpene saponins from the leaves of Stauntonia hexaphylla

Using various chromatographic techniques, 23 triterpene saponins (1–23) were isolated from an ethanol extract of Stauntonia hexaphylla, including two new compounds (12 and 15). Their chemical structures were established by comprehensive spectroscopic methods such as 1D- and 2D-NMR, and HR-ESI-MS, and chemical reactions. The anti-inflammatory activities of the isolated saponins were determined using the nitric oxide (NO) assay. Compound 13 exhibited the greatest inhibitory effect (IC₅₀?=?0.59?μM). In addition to NO, compound 13 suppressed the secretion of PGE₂, IL-1β, and IL-6, but not TNF-α, and inhibited the protein expression of iNOS and COX-2 in LPS-activated RAW264.7 cells. The chemical derivatives of the isolated compounds were studied using structure–activity relationships. The results suggested that compound 13 isolated from S. hexaphylla might be useful for treating inflammation. This is the first comprehensive study of saponins from the leaves of S. hexaphylla based on anti-inflammatory extract screening guidelines.     

Anticomplement compounds from Polygonum chinense

Five new compounds including two phenyldilactones (1, 2), two coumarins (3, 4) and a dimer of N-E-feruloyl tyramine (5) together with twenty-three known compounds (6–28) were isolated from a medicinal plant Polygonum chinense. The structures of the new compounds were established by detailed spectral analysis. The absolute configurations of 1 and 5 were elucidated by Mosher’s method, Mo₂(OAc)₄-induced electronic circular dichroism (ECD) data, and ECD calculation. All the compounds were found to show potent anticomplement activity with CH₅₀ and AP₅₀ values ranging from 0.18 to 1.45?mM, and 0.26 to 2.80?mM, respectively. Phenyldilactones and phenylpropionic tyramines were firstly reported as anticomplement agents. The targets of compounds 1, 3, 5 and 10 in complement activation cascade were identified as well.     

Anti-inflammatory isoflavones and isoflavanones from the roots of Pongamia pinnata (L.) Pierre

A phytochemical study on the roots of Pongamia pinnata afforded five new isoflavone and isoflavanone derivatives (1–5), including two previously undescribed phenylisoflavones possessing an 1,2-oxetane ring, along with 21 known compounds (6–26) among which compound 18 is the first time to be isolated from nature. The structures of the isolated compounds were determined on the basis of 1D, 2D NMR, and HRESIMS. The absolute configurations of the compounds were assigned via analysis of the specific rotations and circular dichroism (CD) spectra, as well as by comparison of the calculated and experimental electronic circular dichroism (ECD) data. All the isolated compounds were evaluated for their inhibitory effects on NO production in LPS-stimulated BV-2 microglial cells. Twelve compounds exhibited different levels of inhibitory effects against NO production, and compound 1 showed the best activity with an IC₅₀ value at 9.0?μM.     

Two novel isoflavone derivatives from Ficus esquiroliana Levl. and their cytotoxic effects on cancer cells

Two novel isoflavone derivatives ficusavone A and B (1 and 2) together with two known biogenetically related isoflavone derivatives (3 and 4) were isolated from the stems of Ficus esquiroliana Levl. The structures of these compounds were elucidated using comprehensive spectroscopic methods. Compounds 1 and 2 represent the rare example of an isoflavone derivative of oxidative cracking of isopentene from natural products. The inhibitory activities of all compounds against HeLa, MCF-7 and A549 cells were evaluated. Compound 1 showed the cytotoxicity against the MCF-2 (IC₅₀ = 12.3 μM) and A549 (IC₅₀ = 17.8 μM) cell lines. The other compounds showed modest activities or were inactive.     

Lignan derivatives from Selaginella tamariscina and their nitric oxide inhibitory effects in LPS-stimulated RAW 264.7 cells

The chemical characterization of Selaginella tamariscina leaves resulted in the isolation of five lignanoside derivatives (1–4 and 6) and one neolignan (5). These compounds include three new lignanosides, tamariscinosides D–F (1–3), and one liriodendrin (4) that were isolated for the first time from this plant, together with two known compounds, (2R,3S)-dihydro-2-(3,5-dimethoxy-4-hydroxyphenyl)-7-methoxy-5-acetyl-benzofuran (5) and moellenoside B (6). The chemical structures of these isolated compounds were determined using 1D and 2D NMR, MS, and CD spectroscopic data, and the results were compared to data previously reported in the literatures. These compounds were also evaluated in terms of their inhibition of NO production in lipopolysaccharide (LPS)-stimulated activity in the macrophage cell line RAW 264.7. Among them, compounds 1, 2, 5, and 6 exhibited a significant inhibition with IC₅₀ values ranging from 32.3 to 55.8 μM.     

Two new compounds from the aerial parts of Elsholtzia densa

Two new compounds, named edensa acid (1), and edensaoside A (2), as well as twenty-nine known compounds (3–31) were isolated from the aerial parts of Elsholtzia densa Benth. The chemical structures of the new compounds were determined by spectrometric data interpretation using NMR, HRESIMS, IR and UV spectroscopy. In addition, all compounds were evaluated for their anti-influenza virus activities against A/WSN/33(H1N1). Among these, compounds 18 and 19 exhibited moderate anti-influenza virus activities with IC₅₀ values of 18.79 μM and 59.87 μM respectively.     

Bioactive secondary metabolites from the marine-associated fungus Aspergillus terreus

Three new compounds, including a prenylated tryptophan derivative, luteoride E (1), a butenolide derivative, versicolactone G (2), and a linear aliphatic alcohol, (3E,7E)-4,8-dimethyl-undecane-3,7-diene-1,11-diol (3), together with nine known compounds (4–12), were isolated and identified from a coral-associated fungus Aspergillus terreus. Their structures were elucidated by HRESIMS, one- and two-dimensional NMR analysis, and the absolute configuration of 2 was determined by comparison of its electronic circular dichroism (ECD) spectrum with the literature. Structurally, compound 1 featured an unusual (E)-oxime group, which occurred rarely in natural products. Compounds 1–3 were evaluated for the α-glucosidase inhibitory activity, and compound 2 showed potent inhibitory potency with IC₅₀ value of 104.8 ± 9.5 μM, which was lower than the positive control acarbose (IC₅₀ = 154.7 ± 8.1 µM). Additionally, all the isolated compounds were evaluated for the anti-inflammatory activity against NO production, and compounds 1–3, 5–7, and 10 showed significant inhibitory potency with IC₅₀ values ranging from 5.48 to 29.34 μM.     

New secondary metabolites from Dodonaea viscosa

Bioassay guided fractionation and chemical investigation of the ethanolic extract of the aerial parts of Dodonaea viscosa Linn. from Egypt, resulted in the isolation and identification of three new compounds, including two new clerodane diterpenoids 1 and 2 and a new myo-inositol derivative 3, along with nine known compounds 4–12. The structures of the isolated compounds were elucidated using 1D and 2D NMR experiments, HRESIMS, and comparison with literature data. All isolated compounds were evaluated for their antibacterial, antifungal, antimalarial as well as antileishmanial activities. Compound 5 exhibited good antifungal activity against Cryptococcus neoformans with an IC₅₀ value of 6.11 μg/ml. Compounds 10 and 12 showed moderate antileishmanial activity against Leishmania donovani with IC₅₀ values of 16.6 and 19.06 μg/ml, respectively.     

Bioactive constituents from the leaves of Croton tiglium

Fifteen compounds, including five new phorbol esters (1-5) and ten known metabolites were isolated from the leaves of Croton tiglium. The structures of new compounds 1-5 were determined by comprehensive analysis of the HRESIMS, IR, 1D and 2D NMR spectral data. The isolates were assayed for their larvicidal and α-glucosidase inhibitory activity; results suggested the new compounds 1-4 possessed significant insecticidal activity, inhibiting the Plutella xylostella with LC₅₀ values ranging from 0.081 to 0.114 μg/mL, while the sesquiterpenoids 11 and 15 showed noticeable α-glucosidase inhibitory activity with IC₅₀ values of 11.27 and 8.13 μM, respectively.     

Antileishmanial activity and ultrastructural changes of sesquiterpene lactones isolated from Calea pinnatifida (Asteraceae)

Bioactivity-guided fractionation of antileishmanial active CH₂Cl₂ phase of MeOH extract from leaves of Calea pinnatifida led to isolation of two sesquiterpene lactones calein C (1) and calealactone C (2), which structures were stablished on the basis of spectroscopic analysis. Compounds 1 and 2 displayed potent activity against Leishmania amazonensis promastigotes with EC₅₀ of 1.7 and 4.6 µg mL⁻¹, respectively. Compound 2 presented low cytotoxicity for J774 macrophages and displayed activity against amastigote forms of L. amazonensis similar to miltefosine with CC₅₀ values of 31.73 and 27.18 µg mL⁻¹, respectively. Additionally, compounds 1 and 2 caused ultrastructural changes in promastigotes leading to a loss of their classical structural morphology, as evidenced by electron microscopy. Also compound 2 decreased the mitochondria membrane potential. To the best of our knowledge, this is the first occurrence of 1 and 2 in C. pinnatifida. The results obtained highlighted the importance of studying sesquiterpene lactones isolated from Calea pinnatifida in terms of antileishmanial activity, in order to understand the mechanism of action of the isolated compounds in promastigotes forms of L. amazonensis.     

C-methylated flavonoids from Pisonia grandis roots

Five new C-methylated flavonoids (1–5) together with seven known compounds have been isolated after chromatographic separation of the hexane and CH₂Cl₂ extracts of the roots of Pisonia grandis (Nyctaginaceae). Structural identification of the new compounds was accomplished by spectroscopic methods. The radical scavenging and antimicrobial properties of the isolates were investigated.