Anti-liver cancer constituents from the thorns of Gleditsia sinensis

Four new long-chain esters of trans-ferulic acid (1–4) were isolated from the thorns of Gleditsia sinensis, together with eight known compounds (5–13). The structure elucidations were achieved by in-depth spectroscopic examination, mainly including multiple 1D- and 2D-NMR and HRESIMS experiments and analyses. Cytotoxic activities of these compounds were evaluated against human liver cancer SK-hep-1 cell line by the MTT in vitro assay. Among them, compound 13 exhibited potent cytotoxic activity with IC₅₀ value of 38.18 μM, and compounds 7 and 8 showed moderate cytotoxic activities with IC₅₀ values of 58.11 and 54.61 μM, respectively.     

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.     

Cytotoxic and anti-inflammatory effects of lignans and diterpenes from Cupressus macrocarpa

Cupressus macrocarpa is a windbreak tree and is reported to have various cytotoxic effects. A natural product study on the leaves of C. macrocarpa has yielded ten secondary metabolites, including three new diterpenoids (1–3), four known diterpenoids (4–7), and three known lignans (8–10). The structures of all isolated compounds were elucidated via the interpretation of spectroscopic methods, especially 2D NMR and mass analyses. In the cytotoxic assays, compounds 1–3 and 7–10 showed inhibition effect against HepG2, MDA-MB-231, and A549 cells with IC₅₀ values ranging from 0.004 to 19.9 μg/mL. Moreover, the anti-inflammatory assays revealed that (−)-matairesinol (8) had significant inhibitory activities on superoxide anion generation (IC₅₀ = 2.7 ± 0.3 μM) and elastase release (IC₅₀ = 6.6 ± 0.7 μM).     

Two new rotenoids from the roots of Millettia speciosa

Two new rotenoids, named millettiaosas A–B (1–2), together with four known compounds were isolated from the roots of Millettia speciosa. Their structures were elucidated on the basis of spectroscopic analysis including 1D and 2D NMR techniques and HRESIMS. Evaluation of the two new compounds for cytotoxicity against four human cancer cell lines (MCF-7, HCT-116, A549 and HepG-2) showed moderate activities (10 μM < IC₅₀ < 26 μM).     

Daphnane-type diterpenes with inhibitory activities against human cancer cell lines from Daphne genkwa

Four new daphnane-type diterpenes, genkwadanes A–D (1–4), together with 19 known ones, were isolated from ethanol extract of the flower buds of Daphne genkwa. Their structures were determined on the basis of extensive spectroscopic data. Among them, daphnane-type diterpene with a 1,10-double bond (1) was isolated from this plant for the first time. The cytotoxicity of all compounds 1–23 against the 10 selected human cancer cell lines was assayed. A number of compounds exhibited significant activities against the 10 cancer cell lines (IC₅₀ < 9.56 μM). and most interestingly, all the compounds revealed preferred cytotoxicities on the HT-1080 cell line and displayed much stronger inhibitory activities (IC₅₀ < 29.94 μM) compared with positive control 5-fluorouracil (IC₅₀ = 35.62 μM), particularly, compounds 9–11, 13, 16 and 19 exhibited the strongest cytotoxicity activities against the HT-1080 cell line (IC₅₀ < 0.1 μM).     

α-Glucosidase inhibitory and nitric oxide production inhibitory activities of alkaloids isolated from a twig extract of Polyalthia cinnamomea

The first phytochemical investigation of Polyalthia cinnamomea led to the isolation and identification of two new oxoprotoberberine alkaloids, (−)-(13aS)-polyalthiacinnamines A and B, together with eleven known compounds. The structures of the new compounds were elucidated by extensive spectroscopic methods. The absolute configuration of miliusacunine E and consanguine B was established by X-ray diffraction analysis using Cu Kα radiation and ECD spectra, whereas the absolute configurations of polyalthiacinnamines A and B were established by comparison of their ECD spectra and specific rotations with those of miliusacunine E and consanguine B. Compounds 1–4, 6, and 8 exhibited α-glucosidase inhibitory activities (IC₅₀ values ranging from 11.3 to 57.9 µM) better than a positive control (acarbose, IC₅₀ 83.5 μM). Compound 2 also exhibited NO production inhibitory activity with an IC₅₀ value of 24.4 μM (indomethacin, a positive control, IC₅₀ = 32.2 μM).     

New phenolic glycosides with cyclooxygenase inhibition from the roots of Tecoma mollis

Three new phenolic glycosides (1–3) together with nine known ones were isolated from the roots of Tecoma mollis using DPPH radical scavenging bioassay-guided chromatographic separation. The structures of the new compounds were established using extensive spectroscopic data and HR-MS. The antioxidant, COX-2 inhibition, and cytotoxic activities were evaluated for the isolated compounds. Compound 4 displayed the strongest radical scavenging activity relative to ascorbic acid with IC₅₀ 8.7 μM. Compounds 5, 6, and 10 showed promising COX-2 inhibitory action, IC₅₀ values of 11.3 μM, 9.4 μM, and 13.4 μM, respectively. All compounds exhibited weak cytotoxic activity against Hela and A549 cancer cell lines.     

Synthesis and biological evaluation of novel C5 halogen-functionalized S-DABO as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

A series of novel S-DABO analogues (4a1–5a12) have been synthesized by an efficient method and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). The biological testing results clearly indicated that the substitution of halogen at the C5 position of pyrimidine ring could increase the anti-HIV-1 RT activity. The most active compounds showed activity in the low micromole range with IC₅₀ values (IC₅₀ 0.18–3.03 μM) comparable to nevirapine (IC₅₀ 4.12 μM). The docking showed that a new halogen bond was formed between halogen and carbonyl of TYR188 in the HIV-I RT.     

Design,synthesis, antiviral and cytostatic activity of ω-(1H-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues

The efficient synthesis of a new series of polyhydroxylated dibenzyl ω-(1H-1,2,3-triazol-1-yl)alkylphosphonates as acyclic nucleotide analogues is described starting from dibenzyl ω-azido(polyhydroxy)alkylphosphonates and selected alkynes under microwave irradiation. Selected O,O-dibenzylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and for cytostatic activity against murine leukemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Compound (1S,2S)-16b exhibited antiviral activity against Influenza A H3N2 subtype (EC₅₀ = 20 μM—visual CPE score; EC₅₀ = 18 μM—MTS method; MCC >100 μM, CC₅₀ >100 μM) in Madin Darby canine kidney cell cultures (MDCK), and (1S,2S)-16k was active against vesicular stomatitis virus and respiratory syncytial virus in HeLa cells (EC₅₀ = 9 and 12 μM, respectively). Moreover, compound (1R,2S)-16l showed activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC₅₀ = 2.9 and 4 μM, respectively) and feline herpes virus in CRFK cells (EC₅₀ = 4 μM) but at the same time it exhibited cytotoxicity toward uninfected cell (MCC ⩾ 4 μM). Several other compounds have been found to inhibit proliferation of L1210, CEM as well as HeLa cells with IC₅₀ in the 4–50 μM range. Among them compounds (1S,2S)- and (1R,2S)-16l were the most active (IC₅₀ in the 4–7 μM range).     

Tirucallane triterpenoids from the stem bark of Araliopsis synopsis

Two new tirucallane triterpenoids, 21-methoxy-21,23-epoxy-tirucalla-7,24-dien-3α-ol (1) and 21-methoxy-21,23-epoxy-tirucalla-7,24-diene-1α,3α-diol (2), together with thirteen known compounds were isolated from the CH₂Cl₂ extract of the stem bark of Araliopsis synopsis. The structures of the compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data and comparison with previously known analogs. Compounds 1–10 were tested against bacteria, fungi and plant pathogen oomycetes by the paper disk agar diffusion assay resulting in missing to low activities corresponding with MICs > 1 mg/mL. However, compounds 5–10 exhibited high cytotoxic activity against the human Caucasian prostate adenocarcinoma cell PC-3 line, with IC₅₀ 8.5–12.5 μM compared to the standard Doxorubicin with IC₅₀ = 0.9 μM, while compounds 1, 3 and 4 showed low activity.     

Antidiabetic triterpenoids from the leaves of Paeonia suffruticosa and Paeonia delavayi

Three new nor-oleanane triterpenoids, paeonenoides I-K (1-3), together with 13 known triterpenoids including nor-oleanane, oleanane, ursane, and cycloartane types, were isolated from the leaves of Paeonia suffruticosa and P. delavayi. The structures of the new compounds were elucidated with the aid of HRESIMS, 1D and 2D NMR, IR, and [α]_D spectroscopic methods. Nine compounds (5-6, 8-11, 13-14 and 16) showed inhibition against PTP1B with IC₅₀ values ranging from 36.5 to 192.6 μM, six compounds (5-6, 8-10 and 14) exhibited inhibitory activity against GPa with IC₅₀ values ranging from 39.8 to 108.0 μM, and five compounds (1, 6, 10, 15 and 16) could significantly stimulate GLP-1 secretion by 100.2–313.4% (20 μM). Docking study demonstrated that compounds 5 and 6 strongly bonded with Gpa and PTP1B by salt bridges, hydrogen bonds and hydrophobic interactions, verifying the importance of carboxyl and hydroxyl groups. Especially, compounds 5 and 14 could simultaneously inhibit PTP1B and GPa with IC₅₀ values of 57.8, 47.9 μM and 39.8, 45.2 μM, and compounds 6 and 10 could stimulate GLP-1 secretion by 293.6% and 313.4% at 20 μM.     

Isolation,structural characterization and neuraminidase inhibitory activities of polyphenolic constituents from Flos caryophylli

Neuraminidase (NA) is one of the key surface proteins of the influenza virus, which is an important target for anti-influenza therapy. In the present study, bioassay-guided fractionation led to isolation of two new compounds, rhamnetin-3-O-β-d-glucuronide-6″-methyl ester (1) and rhamnazin-3-O-β-d-glucuronide-6″-methyl ester (2), along with seventeen known compounds (3-19), from the MeOH extract of Flos Caryophylli using in vitro NA inhibition assay. These isolated compounds exhibited significantly inhibitory effects on the NA with IC₅₀ values ranging from 8.4 to 94.1 μM and were found to protect MDCK cells from A (H1N1) influenza infections (EC₅₀ = 1.5–84.7 μM) with very low cytotoxicity to the host cells (CC₅₀ = 374.3–1266.9 μM)), with selective index (SI) ranging from 7 to 297. The primary structure-relationships of these isolates were also discussed.     

Two new polyhydroxylated steroidal glycosides from Paris polyphylla var. yunnanensis

Chemical investigation of Paris polyphylla smith var. yunnanensis afforded two new polyhydroxylated steroidal glycosides, named Parisyunnanosides K and L (1–2), together with nine known ones. The chemical structures of the new compounds were elucidated by 1D, 2D NMR and HR-ESI-MS techniques, together with chemical methods. Parisyunnanosides K and L (1–2) are rare C₂₇ steroidal glycosides with two double bonds located at C-5, 6 and C-25, 26 of the aglycone, respectively. The cytotoxic activities of the isolated compounds were evaluated against Caco-2 cells by CCK-8 assay. Among them, compounds 5–11 exhibited potent cytotoxic activity with IC₅₀ values ranging from 1.10 to 14.14 μM compared with the positive control oxaliplatin (1.38 μM).     

Cytotoxic triterpene saponins from the stem bark of Kalopanax pictus

Three new compounds, 3β,6β,23-trihydroxyolean-12-en-28-oic acid 3-O-α-l-arabinopyranoside (1), kalopanaxsaponin L (2), and kalopanaxsaponin M (13), as well as eleven known compounds (3–12 and 14), were isolated from the stem bark of Kalopanax pictus. Their structures were determined on the basis of extentive spectroscopic analyses and acid hydrolysis. The cytotoxicity of the compounds was evaluated in three human carcinoma cell lines, including HL-60, HCT-116, and MCF-7. Compounds 1, 5–8, 10, and 11 exhibited significantly cytotoxic activity toward HL-60 cells, with IC₅₀ values ranging from 0.1 to 6.9 μM. Compounds 4–7 and 14 showed significant cytotoxicity against HCT-116 cells, with IC₅₀ values ranging from 0.4 to 9.2 μM. Remarkably, the cytotoxic activities of compounds 5–7 against HCT-116 cells were greater than that of the anticancer chemotherapy drug, mitoxantrone (IC₅₀ = 3.7 μM). Compounds 1, 3, 5, and 14 were cytotoxic toward MCF-7 cells with IC₅₀ values in a range of 7.4–14.5 μM.     

Scutelinquanines A–C,three new cytotoxic neo-clerodane diterpenoid from Scutellaria barbata

Three new neo-clerodane diterpenoids, named scutelinquanines A–C (1–3), were isolated from the whole plant of Scutellaria barbata. Their structures were established on the basis of detailed spectroscopic analyses. In vitro, the isolated three new compounds showed significant cytotoxic activities against three human cancer lines (HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells), and gave IC₅₀ values in the range 2.7–6.7 μM.     

Chemical constituents of Mussaenda erythrophylla Schumach. & Thonn. (Rubiaceae) and their chemophenetic significance

The chemical investigation of the CH₂Cl₂/MeOH (1:1) extract from the aerial part of Mussaenda erythrophylla Schumach. & Thonn. (Rubiaceae) resulted in the isolation of sixteen known compounds (1–16) distributed in coumarins, flavonoid glucosides, quinic acid derivatives, triterpenoids, monoglycerid, steroids, tetraterpenoid and polyol. The structures of the compounds were determined by spectrometric and spectroscopic analysis including MS and NMR data followed by their comparison with reported ones in the literature. The chemophenetic significance of the isolated compounds was discussed. The crude extract and some of the isolated compounds were assessed in vitro for their antileishmanial, cytotoxic and antiplasmodial activities. The crude extract of M. erythrophylla showed moderate antileishmanial activity (IC₅₀ = 61.6 μg/mL) while the hexane soluble fraction showed good antileishmanial activity (IC₅₀ = 31.06 μg/mL) compared to the reference drug amphotericin B (IC₅₀ = 0.11 μM). Compounds 11 and 9 also exhibited potent antileishmanial activity (IC₅₀ = 53.7–52.0 μM). The crude extract as well as the ethyl acetate soluble fraction also exhibited good antiplasmodial activity (IC₅₀ = 7.43 ± 0.00 μg/mL and 14.49 ± 2.96 μg/mL respectively), while compounds 11, 15 and 16 showed weak activity with IC₅₀ > 20 μM compared to the reference drug artemisinin (IC₅₀ = 0.014 ± 0.001 μM).     

Identification and evaluation of apoptotic compounds from Garcinia paucinervis

Four new compounds, paucinervins A–D (1–4), and 15 known ones were isolated from the leaves of Garcinia paucinervis. The structures of the new compounds were elucidated by spectroscopic evidences. All of the 19 compounds were evaluated for their apoptosis-inducing effects using HeLa-C3 cells which have been genetically engineered to possess a fluorescent biosensor capable of detecting caspase-3 activation. Eight of them were found to activate caspase-3 in HeLa-C3 cells within 72 h at the concentration of 25 μM. Moreover, the values of IC₅₀ were measured for all four new compounds on HeLa cells using the MTT assay. Among them, compound 2 (paucinervin B) had the lowest IC₅₀ value of 9.5 μM, while the other three new compounds had much higher IC₅₀ values of 29.5, 52.5, and 95.6 μM, respectively. This result shows that paucinervin B has the strongest inhibitory effect against HeLa cell growth among these four newly identified paucinervins and it may have the potential to be developed into a new anticancer candidate.     

Acridone alkaloids from Vepris verdoorniana (Excell & Mendonça) Mziray (Rutaceae)

Two new acridone alkaloids, verdoocridone A (1) and B (4), together with fifteen known compounds were isolated from methanol extracts of the roots and leaves of Vepris verdoorniana. The structures of all compounds were determined by comprehensive spectroscopic analyses (1D and 2D NMR, EI- and ESI–MS). The ¹³C NMR values of 1,2,3,5-tetramethoxy-N-methylacridone (2) and 5-methoxyaborinine (3) are also reported. The crude extracts and compounds (1-6) were tested for their antimicrobial activity. The test delivered moderate activities for crude extracts and compounds 1, 5 and 6 against the bacterium Staphylococcus aureus and the fungi Mucor meihei and Candida albicans with MIC values between 115 and 180 μg/mL for extracts and between 21.3 and 29.4 μM for compounds, compared to gentamycin with 0.2 μM and nystatin with 5.2 μM against both fungi. The determination of the radical scanvenging activity using 1,1-dephenyl-2-picrylhydrazyl (DPPH) assay gave moderate antioxidant values for all tested compounds, with IC₅₀ between 0.29 and 0.41 μM, compared to the standard 3-t-butyl-4-hydroxyanisole (BHA) displaying 0.03 μM.     

Aethusifolins A–D: Four new components from a traditional Mongolian medicinal herb Clematis aethusifolia Turcz

Four new components named aethusifolins A–D (1–4), together with ten known (5–14) were isolated from the dried aerial parts of a traditional Mongolian medicinal herb Clematis aethusifolia Turcz. The planar structures were established based on extensive spectroscopic analysis (HRMS, 1D and 2D NMR), and the absolute configurations were determined by modified Mosher’s method, hydrolysis method. The cytotoxicities of isolated compounds against a panel of five human solid tumor cell lines were assayed. Compounds 5, 8, and 13 showed moderate cytotoxicity against A-375 with IC₅₀ values of 15–18 μM, while compound 8 also showed cytotoxicity against SH-SY5Y with IC₅₀ values of 20 μM.     

Antiproliferative cardenolide glycosides of Elaeodendron alluaudianum from the Madagascar Rainforest

Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of Elaeodendron alluaudianum led to the isolation of two new cardenolide glycosides (1 and 2). The ¹H and ¹³C NMR spectra of both compounds were fully assigned using a combination of 2D NMR experiments, including ¹H–¹H COSY, HSQC, HMBC, and ROESY sequences. Both compounds 1 and 2 were tested against the A2780 human ovarian cancer cell line and the U937 human histiocytic lymphoma cell line assays, and showed significant antiproliferative activity with IC₅₀ values of 0.12 and 0.07 μM against the A2780 human ovarian cancer cell line, and 0.15 and 0.08 μM against the U937 human histiocytic lymphoma cell line, respectively.