Steroid glycosides from the starfish Pentaceraster gracilis

Using combined chromatographic separations, two new steroid glycosides namely pentacerosides A (1) and B (2), and four known compounds were isolated from the methanol extract of the starfish Pentaceraster gracilis. Their structures were determined on the basis of spectroscopic data (¹H and ¹³C NMR, HSQC, HMBC, ¹H-¹H COSY, ROESY, and FT-ICR-MS) and by comparing obtained results to the literature values. Among the isolated compounds, only maculatoside (5) showed significant cytotoxic effect against Hep-G2 (IC₅₀ = 16.75 ± 0.69 μM) and SK-Mel2 (IC₅₀ = 19.44 ± 1.45 μM) cell lines and moderate effect on KB (IC₅₀ = 36.53 ± 0.78 μM), LNCaP (IC₅₀ = 39.75 ± 3.34 μM), and MCF7 (IC₅₀ = 47.34 ± 7.01 μM) cell lines.     

Two new sesquiterpenoid glycosides from the leaves of Lycium barbarum

Two new sesquiterpenoid glycosides, lyciumionosides A–B (1–2), together with four known compounds (3–6), were isolated from the leaves of Lycium barbarum. Their structures were mainly established on the basis of MS, 1D and 2D NMR spectroscopic techniques. The antiproliferative activities of compounds 1–5 were evaluated. Compound 1 showed highest inhibitory activity against A549 cells with IC₅₀ value of 32.6 ± 2.6 μM, compound 3 showed highest inhibitory activity against PC-3 cells with IC₅₀ value of 36.0 ± 2.9 μM, and compound 5 exhibited highest inhibitory activity against HeLa cells with IC₅₀ value of 32.3 ± 4.2 μM.     

A new N-methoxyl-carbonyl benzylisoquinoline from Litsea cubeba

A new benzylisoquinoline alkaloid (?)-N-methoxycarbonyl-norjuziphine (1) was isolated from Litsea cubeba. Its structure was identified by extensively spectroscopic techniques and confirmed by the single-crystal X-ray diffraction analysis. Compound 1 showed cytotoxicity against HL-60 and MCF-7 cells, with IC₅₀ values of 18.1 and 15.0 μM, respectively, comparable to 3.1 and 17.5 μM of the cisplatin (positive control).     

A new bioactive steroidal ketone from the South China Sea sponge Xestospongia testudinaria

A new steroidal ketone (1), with an ergosta-22,25-diene side chain, was obtained from the South China Sea marine sponge Xestospongia testudinaria. The structure of 1 was determined on the basis of detailed spectroscopic analysis and by comparison with literature. Compound 1 exhibited significant inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of type II diabetes and obesity, with an IC₅₀ value of 4.27 ± 0.55 μM, which is comparable with the positive control oleanolic acid (IC₅₀ = 2.63 ± 0.22 μM).     

Selective cytotoxic eremophilane-type sesquiterpenes from Penicillium citreonigrum

Abstract

One new eremophilane-type sesquiterpene (1, citreopenin) was isolated from Penicillium citreonigrum (HQ738282), and the structure was elucidated by a combination of spectroscopic data interpretation and single-crystal X-ray diffraction analysis using Cu Kα radiation (CCDC 1030588). Compound 1 showed weak activity against KB-VIN (IC₅₀ = 11.0 ± 0.156 μM), while the known compound 3 exhibited selective cytotoxicity against MDA-MB-231 triple-negative breast cancer (TNBC) (IC₅₀ = 5.42 ± 0.167 μM).     

Two new compounds from the broth of the marine fungus Penicillium griseofulvum Y19-07

Two new compounds, 4-hydroxyphenethyl methyl succinate (1) and 4-hydroxyphenethyl 2-(4-hydroxyphenyl)acetate (2), were isolated from the EtOAc extract of the broth of the marine fungus Penicillium griseofulvum Y19-07. Five known compounds were also obtained in this study. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. All of the isolates were evaluated for their scavenging properties toward the 2,2-diphenyl-1-picrylhydrazyl free radical by spectroscopic assays. Also, in the cytotoxicity assay of the two new compounds against HL-60 and PC-3 prostate cancer cell lines, compound 2 showed potential activity with an IC₅₀ value of 64.5 μM against human HL-60 cancer cells.     

Multidrug resistance protein 1 (ABCC1) confers resistance to arsenic compounds in human myeloid leukemic HL-60 cells

Arsenic trioxide (As₂O₃) is established as one of the most effective drugs for treatment of patients with acute promyelocytic leukemia, as well as other types of malignant tumors. However, HL-60 cells are resistant to As₂O₃, and little is known about the underlying resistance mechanism for As₂O₃ and its biomethylation products, namely, monomethylarsonous acid (MMA^III) on the treatment of tumors. In the present study, we investigated the molecular mechanisms underlying iAs^III and its intermediate metabolite MMA^III-induced anticancer effects in the HL-60 cells. Here, we show that the HL-60 cells exhibit resistance to inorganic iAs^III (IC₅₀ = 10 μM), but are relatively sensitive to its intermediate MMA^III (IC₅₀ = 3.5 μM). Moreover, we found that the multidrug resistance protein 1 (MRP1), but not MRP2, is expressed in HL-60 cells, which reduced the intracellular arsenic accumulation, and conferred resistance to inorganic iAs^III and MMA^III. Pretreatment of HL-60 with MK571, an inhibitor of MRP1, significantly increased iAs^III and MMA^III-induced cytotoxicity and arsenic accumulations, suggesting that the expression of MRP1/4 may lead to HL-60 cells resistance to trivalent arsenic compounds.     

Prenylated isoflavones from Cudrania tricuspidata inhibit NO production in RAW 264.7 macrophages and suppress HL-60 cells proliferation

Inhibitory effects of NO production in RAW 264.7 macrophages guided the isolation of nine prenylated isoflavones, including a new cudraisoflavone L (1) and eight known metabolites furowanin B (2), erysubin A (3), wighteone (4), lupalbigenin (5), laburnetin (6), isolupalbigenin (7), 6,8-diprenylorobol (8), millewanin H (9) from the leaves of Cudrania tricuspidata. At the concentration of 10 μM, compounds 1, 2, and 4 significantly inhibited NO production with the inhibitory values of 72.5 ± 2.4, 66.9 ± 1.8, and 55.4 ± 2.7%, respectively. In addition, all of isolated compounds 1–9 showed promising cytotoxic effects toward HL-60 cells (IC₅₀ 4.3 ± 0.7 to 18.0 ± 1.7 μM).     

Synthesis of some novel orsellinates and lecanoric acid related depsides as α-glucosidase inhibitors

Abstract

Sixteen novel orsellinic esters (6a-l, 7a-d) along with four lecanoric acid related depsides (3a-c, 4) were synthesized and confirmed their structures by spectroscopic data (¹H, ¹³C & HRMS). The synthesized compounds were evaluated for their in vitro α-glucosidase (Saccharomyces cerevisiae) inhibitory potential. Among the tested compounds, 3c (IC₅₀: 140.9 μM) and 6c (IC₅₀: 203.9 μM) displayed potent α-glucosidase inhibitory activity and found more active than the standard drug acarbose (IC₅₀: 686.6 μM). Both the test compounds were subjected to in vivo antihyperglycemic activity using sucrose loaded model in Wistar rats and found compound 3c exhibited significant reduction in glucose levels.     

Brominated polyunsaturated lipids with protein tyrosine phosphatase-1B inhibitory activity from Chinese marine sponge Xestospongia testudinaria

A new brominated polyunsaturated lipid, methyl (E,E)-14,14-dibromo-4,6,13-tetradecatrienoate (1), along with three known related analogues (2–4), were isolated from the Et₂O-soluble portion of the acetone extract of Chinese marine sponge Xestospongia testudinaria treated with diazomethane. The structure of the new compound was elucidated by detailed spectroscopic analysis and by comparison with literature data. Compound 3 exhibited significant inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of type II diabetes and obesity, with an IC₅₀ value of 5.30 ± 0.61 μM, when compared to the positive control oleanolic acid (IC₅₀ = 2.39 ± 0.26 μM).     

Synthesis of indole-2-hydrazones in search of potential leishmanicidal agents

Indole-2-hydrazones 3–30 were synthesized and evaluated for their antileishmanial activity. The compounds 24 (IC₅₀ = 1.86 ± 0.09 μM), 12 (IC₅₀ = 2.26 ± 0.16 μM), 23 (IC₅₀ = 3.81 ± 0.29 μM), 8 (IC₅₀ = 4.01 ± 0.32 μM), 17 (IC₅₀ = 4.89 ± 0.31 μM), 20 (IC₅₀ = 4.89 ± 0.26 μM), 3 (IC₅₀ = 5.12 ± 0.34 μM), 15 (IC₅₀ = 5.26 ± 0.26 μM), 6 (IC₅₀ = 6.16 ± 0.38 μM), and 21 (IC₅₀ = 6.18 ± 0.045 μM) showed better activities than standard pentamidine (IC₅₀ = 7.02 ± 0. 09 μM). Compounds 4, 5, 7, 9–11, 13, 16, 18, 19, 22, 25–28, and 30 displayed good activities. The compounds 14 and 29 were found to be inactive. The synthesized compounds were characterized by different spectroscopic techniques.     

Two pairs of rare naturally occurring 4-hydroxy-4-methyl-2,5-heptanedione derivatives from the red alga Chondria crassicaulis

Two pairs of rare naturally occurring racemic lipids, (±)-4,7-dihydroxy-4-methyl-2,5-heptanedione (1), and (±)-7-butoxy-4-hydroxy-4-methyl-2,5-heptanedione (2) were isolated from the red alga Chondria crassicaulis Harv. The structures of the racemic mixtures of 1 and 2 were elucidated by detailed spectroscopic techniques, including 1D and 2D NMR (¹H and ¹³C NMR, ¹H–¹H COSY, HSQC, and HMBC) as well as mass spectrometry and optical rotation experiments, and by comparison with data for related known analogs. This is the first report of naturally occurring 4-hydroxy-4-methyl-2,5-heptanedione derivatives. Antifungal, PTP1B inhibitory, and receptor tyrosine kinase inhibitory activities of these two compounds were investigated. The results showed that compounds 1 and 2 exhibited good selective inhibition against RET tyrosine kinase activity with IC₅₀ values of 9.56 and 8.93 μM, respectively. Compound 1 also displayed moderate antifungal activity against Cryptococcus neoformans (32609), showing a MIC₈₀ value of 32 μg/ml.     

(±) Cochlearoids N–P: three pairs of phenolic meroterpenoids from the fungus Ganoderma cochlear and their bioactivities

Three pairs of meroterpenoids (±) cochlearoids N–P (1–3) were isolated from the fruiting bodies of Ganoderma cochlear. Their structures including absolute configurations were assigned by spectroscopic techniques. All the isolated compounds were tested for their inhibitory activities toward BRD4, human cancer cells, and micro-organisms. The results show that the enantiomers of (±)-1 are BRD4 inhibitors, (?)-1 and (+)-3 are cytotoxic against human cancer cells (K562) with IC₅₀ values of 7.68 and 6.68 μM, respectively. Besides compounds (±)-2 and (±)-3 exhibit potent inhibitory activity against Staphylococcus aureus with IC₅₀ values in the range of 5.43–17.99 μM.     

Structure determination of two new C21 steroidal glycosides from Cynanchum komarovii

Abstract

Two new 13,14:14,15-disecopregnane-type C₂₁ steroidal glycosides, namely komarosides R (1) and S (2), along with four known compounds (3–6), were obtained from the 95% ethanol extract of the whole herbs of Cynanchum komarovii Al.Iljinski (Asclepiadaceae). The structures of new compounds were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. Compounds 1 and 2 showed potent inhibitory activities against human leukemia cell line (HL-60) with IC₅₀ values being 6.2 and 17.6 μM, respectively, compared to the positive control 5-fluorouracil (6.4 μM).     

Six new C-21 steroidal glycosides from Dregea sinensis Hemsl

Six new C-21 steroidal glycosides (1–6) were separated from the root of Dregea sinensis Hemsl. and their structures were elucidated using extensive nuclear magnetic resonance, mass spectrometry, and infrared spectral analyses. Isolated compounds were evaluated for antitumor activity, which showed that compound 3 had moderate activity in Jurkat cells (IC₅₀ 19.54 ± 0.91 μM), and compounds 1–4 had significant effects against IL-2R and TNFR2 (IC₅₀ 1.518 ± 0.06 μM to 5.9 ± 0.07 μM).     

Clemochinenosides C and D,two new macrocyclic glucosides from Clematis chinensis

Abstract

The EtOH extract of the roots and rhizomes of Clematis chinensis afforded two new macrocyclic glucosides clemochinenosides C (1) and D (2). Their structures were elucidated on the basis of spectroscopic means and hydrolysis products. These compounds were evaluated for inhibitory activity against lipopolysaccharides-induced TNF-α production in RAW 246.7 macrophages. Compounds 1 and 2 showed moderate inhibitory activity with IC₅₀ values of 12.9 ± 2.3 and 18.4 ± 2.7 μM, respectively. In addition, a proliferation study was used to evaluate the anti-angiogenic effects of these compounds in vitro (VEGF-induced human umbilical vein endothelial cell proliferation). Compounds 1 and 2 displayed weak inhibitory effects with inhibition rates of 26.3 ± 1.8 and 19.2 ± 2.6% at 50 μM, respectively.     

Cytotoxic constituents from the seeds of Vietnamese Caesalpinia sappan

Abstract

Context: Caesalpinia sappan Linn. (Leguminosae) has been used in folk medicines for the treatment of many diseases. The heartwood of this plant contains various phenolic components with interesting biological applications; however, the chemical and biological potentials of the seed of this plant have not been fully explored.

Objective: This study identified the cytotoxic activity of compounds from the seeds of C. sappan.

Materials and methods: The methanol extract of the seed of C. sappan was suspended in H₂O and then partitioned with CH₂Cl₂, EtOAc, and n-BuOH, successively. Diterpenoid compounds were isolated from the CH₂Cl₂-soluble fraction by silica gel column chromatography methods using organic solvents. The compound structures were determined by detailed analysis of NMR and MS spectral data. Cytotoxic activity was measured using a modified MTT assay against HL-60, HeLa, MCF-7, and LLC cancer cells. The activation of caspase-3 enzyme and western blotting assay were performed to confirm inhibitory mechanism of active compound.

Results: Five cassane-type diterpenoids were isolated and identified as phanginin I (1), phaginin A (2), phanginin D (3), phanginin H (4), and phanginin J (5). Compounds 1–4 showed effective inhibition against HL-60 cells with the IC₅₀ values of 16.4?±?1.5, 19.2?±?2.0, 11.7?±?1.6, and 22.5?±?5.1?μM. Compounds 1–3 exhibited cytotoxic activity against HeLa cells with the IC₅₀ values of 28.1?±?3.6, 37.2?±?3.4, and 22.7?±?2.8?μM. Treatment of HL-60 cell lines with various concentrations of 3 (0–30?μM) resulted in the growth inhibition and induction of apoptosis.

Conclusion: These findings demonstrate that compound 3 (phanginin D) is one of the main active components of the seed of C. sappan activating caspases-3 which contribute to apoptotic cell death.     

Selective dual cholinesterase inhibitors from Aconitum laeve

New lycoctonine-type dual cholinesterase inhibitor, swatinine-C (1), along with three known norditerpenoid alkaloids, hohenackerine (2), aconorine (5) and lappaconitine (6) and two synthetically known but phytochemically new benzene derivatives, methyl 2-acetamidobenzoate (3) and methyl 4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate (4), was isolated from the roots of A. laeve. Structures of new and known compounds (1–6) were established on the basis of latest spectroscopic techniques and by close comparison with the data available in literature. In vitro, compounds (1–6) were tested against AChE and BChE inhibitory activities. Compounds 1 and 2 showed competitive inhibition against AChE (IC_50?=?3.7 μM, 4.53 μM) and BChE (IC_50?=?12.23 μM, 9.94 μM), respectively. Compounds 5 and 6 showed promising noncompetitive type of inhibitory profile against AChE (IC_50?=?2.51 and 6.13 μM) only. Compounds 3 and 4 showed weak inhibitory profile against both AChE and BChE.     

Synthesis and anticancer activity of para-xylyl linked bis-benzimidazolium salts and respective Ag(I) N-heterocyclic carbene complexes

The article describes synthesis, characterization (NMR, FT-IR, microanalysis, X-ray crystallography), and in vitro anticancer activity of para-xylyl linked bis-benzimidazolium salts and respective dinuclear Ag–NHC complexes. All the compounds were tested for their cytotoxicity against human colorectal cancer (HCT 116) and promyelocytic leukemia (HL-60) cell lines. According to cell viability measurements using MTT assay, all tested compounds showed dose-dependent cytotoxic activity against both cell lines. The tested compounds demonstrated significant activity with IC₅₀ values range 0.01–18.7 μM for HCT 116 and 0.7–55.7 μM for HL-60 cells. 5-Fluorouracil was used as standard drug (IC₅₀ 19.2 μM for HCT 116 and 5.4 μM for HL-60). We found that as the size of N-alkyl substitution on benzimidazolium salt increases its cytotoxicity decreases whereas a reverse occurred in case of respective complexes.     

Racemosin C,a novel minor bisindole alkaloid with protein tyrosine phosphatase-1B inhibitory activity from the green alga Caulerpa racemosa

A novel minor bisindole alkaloid, racemosin C (1), characterized by a naturally unprecedented 8-hydroxy-2,4,6-cyclooctatrienone ring fused with two indole systems, was isolated from the green alga Caulerpa racemosa, together with one known related metabolite, caulersin (2). The structure of 1 was elucidated on the basis of extensive spectroscopic analysis, and by comparison with the data of related known compounds. A plausible biosynthetic pathway of 1 was proposed. Compounds 1 and 2 exhibited significant PTP1B inhibitory activity with IC₅₀ values of 5.86 ± 0.57 and 7.14 ± 1.00 μM, respectively, compared with the positive control oleanolic acid (IC₅₀ = 3.03 ± 0.20 μM). On the basis of the data obtained, the Caulerpa bisindole alkaloids may be considered as a new class of PTP1B inhibitors.