Cytotoxic arylbenzofuran and stilbene derivatives from the twigs of Artocarpus heterophyllus

Four new natural products, including three arylbenzofurans named heterophyllenes A-C (1–3), and one stilbene named heterophyllene D (4), together with twenty-one known compounds were isolated from the twigs of Artocarpus heterophyllus and their structures elucidated by spectroscopic methods, mainly 1D and 2D NMR spectroscopy. The cytotoxic activity of selected compounds against KB, MCF-7 and NCI-H187 cell lines was evaluated. Heterophyllene C (3) exhibited cytotoxicity against the MCF-7 cell line with an IC₅₀ value of 12.56 μM. Additionally, the known compounds norartocarpin and artocarpin showed cytotoxic activity against MCF-7 and KB cell lines with IC₅₀ values of 10.04 and 13.57 μM, respectively. Both compounds also displayed cytotoxicity against the NCI-H187 cell line with values of 14.78 and 14.21 μM, respectively.     

Synthesis and biological evaluation of novel triazole substituted pyrazolyl-methylenehydrazinyl-5-arylidene thiazolidinone derivatives as antibacterial and cytotoxic agents

Novel triazole substituted pyrazolyl-methylenehydrazinyl-5-arylidene thiazolidinone derivatives 6a–n and 7a–l were synthesized and characterized by Fourier transform infrared, ¹H and ¹³C nuclear magnetic resonance, mass spectrometry and elemental (CHN) analysis. The in vitro antibacterial (6a–n and 7a–l) and cytotoxic (6a–n) activities were evaluated for these compounds. The results revealed that the compounds 6b, 6i, 6k, 7b, 7h displayed good antibacterial activity. The compounds 6c (IC₅₀ = 5.4 μM), 6l (IC₅₀ = 6.3 μM) and 6f (IC₅₀ = 9.85 μM) were effective for inhibition of human breast cancer cell line MCF-7. Similarly, the compounds 6b (IC₅₀ = 8.7 μM) and 6c (IC₅₀ = 9.06 μM) were shown to have effective inhibition on human cervical cancer cell line Hela.     

A contribution to pharmaceutical biology of freshwater sponges

In vitro anti-tumour and anti-radical activities of the acetone extract of the freshwater sponge Ochridaspongia rotunda were the subject of this study. The extract was found to be highly cytotoxic to human lung tumour cell line A-549 reaching IC₅₀ value of 5.01 ± 0.21 μg/mL. Indeed, it displayed only 2-fold less anti-tumour activity than doxorubicin (IC₅₀ value 2.42 ± 0.13 μg/mL) used as a positive control. The same extract was also found to be almost 37-fold more selective against A-549 vs. MRC-5 (normal) lung cells, in difference to weak selectivity of doxorubicin (less than 3-fold). Its profound anti-DPPH radical activity comparable to that of quercetin (IC₅₀ values 3.68 ± 0.19 and 3.14 ± 0.09 μg/mL, respectively) coupled with no signs of genotoxicity in the comet assay (MRC-5 cell line, vs. doxorubicin) has actually implicated the importance of this animal bioresource in searching for pharmaceutically useful bioactive compounds of natural origin.     

Diterpenoids from the gum resin of Boswellia carterii and their biological activities

Seven new diterpenoids, classified as three cembrane-type diterpenoids boscartins I-K (1–3) and four prenylaromadendrane-type diterpenoids boscartols K-N (4–7), respectively, along with nine known diterpenoids, were isolated from the gum resin of Boswellia carterii. Their structure elucidations were achieved by spectroscopic examination. All isolates were evaluated for anti-inflammatory activity against nitric oxide (NO) production and antiproliferative activity against MCF-7 human breast cancer cell in vitro. 4 and 5 exhibited potent inhibitory effects on NO production (IC₅₀ of 2.22 and 1.10?μM, respectively), with 11 showing moderate inhibition (IC₅₀ of 8.63?μM), and 12 and 15 demonstrated moderate antiproliferative effects against MCF-7?cell (IC₅₀ of 9.5, and 6.3?μM, respectively).     

Obionin B: An o-pyranonaphthoquinone decaketide from an unidentified fungus (MSX 63619) from the Order Pleosporales

A fungal extract (MSX 63619), from the Mycosynthetix library of over 50,000 fungi, displayed promising cytotoxicity against a human tumor cell panel. Bioactivity-directed fractionation led to the isolation of an o-pyranonaphthoquinone decaketide, which we termed obionin B (1). The structure of 1 was deduced via spectroscopic and spectrometric techniques. The IC₅₀ value of 1 was moderate, ranging from 3 to 13 μM, depending on the cell line tested.     

Antiplasmodial prenylated flavanonols from Tephrosia subtriflora

The CH₂Cl₂/MeOH (1:1) extract of the aerial parts of Tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone B, and the known flavanonols MS-II (2) and mundulinol. The structures were elucidated by the use of NMR spectroscopy and mass spectrometry. The absolute configuration of the flavanonols was determined based on quantum chemical ECD calculations. In the antiplasmodial assay, compound 2 showed the highest activity against chloroquine-sensitive Plasmodium falciparum reference clones (D6 and 3D7), artemisinin-sensitive isolate (F32-TEM) as well as field isolate (KSM 009) with IC₅₀ values 1.4–4.6 μM without significant cytotoxicity against Vero and HEp2 cell lines (IC₅₀ > 100 μM). The new compound (1) showed weak antiplasmodial activity, IC₅₀ 12.5–24.2 μM, but also showed selective anticancer activity against HEp2 cell line (CC₅₀ 16.9 μM).     

Cytotoxic indolocarbazoles alkaloids from the streptomyces sp. A65

Three new indolocarbazoles alkaloids together with nine known compounds were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. A65. Their structures were elucidated by interpretation of spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS). The absolute configurations of compounds 1 and 2 were determined by single-crystal X-ray crystallographic analysis, and 3 was assigned on the basis of experimental and calculated electronic circular dichroism spectra. All of these compounds were evaluated for cytotoxic activity assay. Compounds 6 and 10 exhibited significant cytotoxicity against PC3 cell lines with IC₅₀ values of 1.96 and 2.92 μM, respectively; Compounds 2 and 3 showed moderate cytotoxic activity with IC₅₀ values of 9.67 and 6.79 μM, respectively. Additionally, compounds 1–4 also were also tested for enzyme inhibition activities of Protein kinase C and Brution tyrosine kinase. They showed moderate activity with IC₅₀ values ranging from 0.25 μM to 1.91 μM except for compound 1, which has no inhibition activity for protein kinase C.     

Eudesmane and aromadendrane sesquiterpenoids from the Vietnamese soft coral Sinularia erecta

Using various chromatographic separations, eight sesquiterpenoids (1–8), including one new compound 3β,5α-dihydroxyeudesma-4(15),11-diene (1), were isolated from the MeOH extract of the Vietnamese soft coral Sinularia erecta. The structure elucidation was confirmed by spectroscopic experiments including 1D and 2D NMR and HR-ESI-MS. The cytotoxic activities against three human cancer cell lines (A-549, HeLa and PANC-1) of all isolated compounds were evaluated by MTT-based colorimetric assays. Compound 1 exhibited selective cytotoxicity against the A549 cell line with IC₅₀ of 14.79 ± 0.91 μM.     

New macrocyclic diterpenes from Euphorbia connata Boiss. with cytotoxic activities on human breast cancer cell lines

Acetone:chloroform (1:2) extract of the aerial parts of Euphorbia connata Boiss. (Euphorbiaceae) was investigated for its diterpenoids. This led to the isolation of one known and two new diterpenes, belonging to the pentahydroxy-13(17)-epoxy-8,10(18)-myrsinadiene and tetrahydroxy-5,6-epoxy-14-oxo-jatropha-11(E)-ene classes. The structures were elucidated based on ¹³C and ¹H NMR as well as 2D NMR, IR and MS spectra and the cytotoxicity for compounds 1–3 were evaluated by using MTT assay against two human breast cancer cell lines. Myrsinane-type compounds – 3,7,14,15-tetraacetyl-5-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (1) and 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene (2) – exhibited moderate inhibitory effects, with IC₅₀ values of 24.53 ± 3.39 and 26.67 ± 1.41 μM against the MDA-MB cell line, and 37.73 ± 3.41 and 34.57 ± 2.12 μM against the MCF-7 cell line, respectively. Jatrophane-type diterpene – 5,6-epoxy-8,9,15-triacetyl-3-benzoyl-14-oxo-jatropha-11(E)-ene (3) – showed weak cytotoxicity, with IC₅₀ values of 55.67 ± 7.09 μM against MDA-MB, and moderate cytotoxicity with IC₅₀ values of 24.33 ± 3.21 μM against MCF-7 cell line.     

Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf

The crude extracts of tubers of Aconitum spicatum (Bruhl) Stapf were investigated for in vitro antileishmanial activity against Leishmania major. The dichloromethane extract at pH 2.5 showed antileishmanial activity with IC₅₀ value of 27.10 ± 0.0 μg/mL. Chromatographic purification of the dichloromethane extract led to isolation of three C-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). Compounds 3 and 2 showed antileishmanial activity with IC₅₀ = 36.10 ± 3.4 and 56.30 ± 2.1 μg/mL, respectively. Compound 1 was less effective (IC₅₀ > 100 μg/mL). The cytotoxicity of compounds 1, 2 and 3 studied against MCF7, HeLa and PC3 cancer cell lines and 3T3 normal fibroblast cell line did not show cytotoxicity at 30 μM.     

Fascioquinols A-F: bioactive meroterpenes from a deep-water southern Australian marine sponge, Fasciospongia sp.

Chemical investigation of a southern Australian deep-water marine sponge, Fasciospongia sp., returned the new meroterpene sulfate fascioquinol A (1) together with a series of acid mediated hydrolysis/cyclization products, fascioquinols B (2), C (3) and D (4), and strongylophorine-22 (5). Additional co-metabolites include the new meroterpenes fascioquinol E (6) and fascioquinol F (8), together with the known sponge metabolite geranylgeranyl 1,4-hydroquinone (7). Structures were assigned to 1-8 on the basis of detailed spectroscopic analysis, chemical interconversion, mechanistic and biosynthetic considerations, and literature comparisons. The known 1,4-hydroquinone 7 was identified as the dominant cytotoxic principle in the Fasciospongia sp. extract, with selective inhibitory activity against gastric adenocarcinoma (AGS, IC₅₀ 8 μM) and neuroblastoma (SH-SY5Y, IC₅₀ 4 μM) cell lines. By contrast, while the fascioquinols displayed little or no inhibitory activity towards human cell lines, 1 and 2 displayed promising Gram-positive selective antibacterial activity towards Staphylococcus aureus (IC₅₀ 0.9-2.5 μM) and Bacillus subtilis (IC₅₀ 0.3-7.0 μM).     

A new 3-alkylpyridine alkaloid from the marine sponge Haliclona sp. and its cytotoxic activity

A new alkaloid, 3-dodecyl pyridine containing a terminal cyano group (1), was isolated from the methanol extract of an Indonesia marine sponge Haliclona sp. Its chemical structure was determined by a combination of spectroscopic methods, including 1D and 2D NMR. Bioassay results indicated that compound 1 had moderate cytotoxity against tumour cell lines A549, MCF-7 and Hela with IC₅₀ values of 41.8, 48.4 and 33.2 μM, respectively.     

Ecionines A and B, two new cytotoxic pyridoacridine alkaloids from the Australian marine sponge, Ecionemia geodides

Chemical investigations of the Australian marine sponge Ecionemia geodides resulted in the isolation of two new pyridoacridine alkaloids, ecionines A (1) and B (2), along with the previously isolated marine natural products, biemnadin (3) and meridine (4). Compounds 1 and 2 both contain an imine moiety, which is rare for the pyridoacridine structure class. The chemical structures of 1 and 2 were determined by extensive 1D and 2D NMR and MS data analyses. All compounds were tested against a panel of human bladder cancer cell lines, the increasingly metastatic TSU-Pr1 series (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2) and the superficial bladder cancer cell line 5637. Ecionine A (1) displayed cytotoxicity against all cell lines, with IC₅₀ values ranging from 3 to 7 μM. This is the first report of chemistry from the sponge genus Ecionemia.     

Triterpene tetraglycosides from the sea cucumber Stichopus horrens

Using various chromatographic separations, three triterpene tetraglycosides (1–3), including one new compound, namely stichorrenoside E (1) along with thelenotoside B (2) and deacetyl thelenotoside B (3), were isolated from the MeOH extract of the Vietnamese sea cucumber Stichopus horrens. Their structures were confirmed by spectroscopic experiments, such as 1D and 2D NMR and HR-ESI-MS. Deacetylated thelenotoside B (3) is firstly isolated as a natural product. Among these compounds, thelenotoside B (2) showed strong cytotoxicities against five human cancer cell lines as HepG2, KB, LNCaP, MCF7 and SK-Mel2 with the IC₅₀ values from 0.95 ± 0.08 to 1.90 ± 0.13 μM, whereas stichorrenoside E (1) and deacetyl thelenotoside B (3) exhibited significant activities with the IC₅₀ values from 6.87 ± 0.25 to 11.62 ± 1.05 μM.     

A new butenolide cinnamate and other biological active chemical constituents from Polygonum glabrum

Phytochemical investigation of the methanol extract of the aerial parts of Polygonum glabrum afforded one new natural product ( ? )-2-methoxy-2-butenolide-3-cinnamate (1) along with six known compounds, β-hydroxyfriedalanol (2), 3-hydroxy-5-methoxystilbene (3), ( ? ) pinocembrin (4), sitosterol-(6′-O-palmitoyl)-3-O-β-d-glucopyranoside (5), ( ? ) pinocembrin-5-methyl ether (6) and sitosterol-3-O-β-d-glucopyranoside (7). Compound 1 showed promising in vitro anti-HIV-1 activity against primary isolates HIV-1_UG070 (X4, subtype D) and HIV-1_VB59 (R5, subtype C) assayed using TZM-bl cell line with IC₅₀ in the range of 15.68–22.43 μg/mL. The extract showed TI in the range of 19.19–27.37 with IC₅₀ in the range of 10.90–15.55 μg/mL. Compounds 1, 3 and 4 exhibited in vitro anti-mycobacterium activity against Mycobacterium tuberculosis H37Ra with IC₅₀ values of 1.43, 3.33 and 1.11 μg/mL in dormant phase and 2.27, 3.33 and 1.21 μg/mL in active phase, respectively. Compound 4 was found to be the most active antiproliferative with IC₅₀ values of 1.88–11.00 μg/mL against THP-1, A549, Panc-1, HeLa and MCF7 cell lines.     

Synthesis, characterisation and in vitro evaluation of palladium(II) iminophosphine complexes for anticancer activity

Palladium(II) complexes have been obtained from the reactions of the iminophosphine ligands, (L1–L7), respectively, with [PdCl₂(COD)] and [PdMeCl(COD)] in CH₂Cl₂ at room temperature. The palladium(II) complexes were characterised using elemental analysis, electro spray ionisation–mass spectrometry (ESI–MS), NMR (¹H and ³¹P), IR spectroscopy and X-ray diffraction studies. Single-crystal X-ray diffraction analysis for complexes 2, 7 and 8 revealed that the complexes exhibited a slightly distorted square planar geometry. In vitro cytotoxic study results show that the palladium complexes exhibit moderate activity and block the proliferation of WHCO1 cells with an IC₅₀ range of 19.02–45.27 μM, and IC₅₀ range of 10.03–68.54 μM for the KYSE450 cell lines.     

The anti-lung cancer activity of propylene tethered dihydroartemisinin-isatin hybrids

Nineteen propylene tethered dihydroartemisinin-isatin hybrids 5a-g and 6a-l were designed, synthesized, and screened for their in vitro antiproliferative activity against three lung cancer cell lines, inclusive of drug-sensitive (A549), doxorubicin-resistant A549 (A549/DOX) and cisplatin-resistant A549 (A549/DDP) cell lines. The cytotoxicity of the synthesized hybrids towards normal lung epithelial cell line (BEAS-2B) was also assessed to evaluate the selectivity. The structure-activity relationship (SAR) elucidated that (1) alkyloxylimino fragment at C-3 position of isatin moiety were more favorable than the carbonyl and benzoxylimino, and the relative contricution order was methoxylimino > ethoxylimino > carbonyl > benzoxylimino; halogen atom at C-5 or C-6 position of isatin fragment could enhance the activity. Among them, hybrid 6f (IC₅₀: 21.7–28.9 μM) showed promising activity against the three tested lung cancer cell lines, and the activity was not inferior to that of cisplatin (IC₅₀: 19.7 and 66.9 μM) and doxorubicin (IC₅₀: 54.3 and 15.1 μM) against multidrug-resistant A549/DOX and A549/DDP lung cancer cell lines. In addition, hybrid 6f (IC₅₀: >100 μM) was non-cytotoxic towards normal lung epithelial cell line (BEAS-2B), and the RI values of hybrid 6f were 1.12 and 1.33. Further, hybrid 6f also possessed acceptable stability in mouse and human microsomes. Accordingly, hybrid 6a was a promising anti-lung cancer chemotherapeutic candidate and merited further evaluations.     

Phenanthrenes from Juncus atratus with antiproliferative activity

The present study has focused on the isolation and structure determination of phenanthrenes from Juncus atratus Krock. Nine compounds, among them five phenanthrenes, have been isolated from the methanol extract of the plant. Two compounds [juncatrins A (1) and B (2)] are new natural products, three phenanthrenes [juncuenin B (3), effusol (4), and dehydroeffusol (5)], the flavones apigenin (7) and luteolin (8), the diterpene phytol and 13(R)-hydroxy-octadeca-(9Z,11E,15Z)-trien-oic acid (9) were isolated for the first time from the plant. Juncatrin A (1) is substitued with an acetyl group, while in case of juncatrin B (2), an unprecedented acetylene group is connected to the phenanthrene skeleton. The isolated phenanthrenes were evaluated for their antiproliferative activity against HeLa, SiHa and MDA-MB-231 human tumor cell lines. Four phenanthrenes (2, 3, 4 and 5) were more effective [IC₅₀s 3.48?μM (2), 2.91 (3), 3.68 (4), and 7.75?μM (5)] than cisplatin (IC₅₀ 12.43?μM) on HeLa cells.     

Ligand fishing and identification of acetylcholinesterase inhibitors in Mahonia bealei (Fort.) Carr. using high performance liquid chromatography-mass spectrometry

Abstract

A fishing platform was developed using immobilized capillary enzyme reactors in combination with liquid chromatography-mass spectrometry (LC-MS) to fish acetylcholinesterase inhibitor (AChEI) from Mahonia bealei (Fort.) Carr. (M. bealei) extract. Four potential AChEIs (columbamine, jatrorrhizine, berberine, and palmatine) were successfully screened out and identified. Their AChE inhibitory activities were further verified by an in vitro assay with IC₅₀ values of 0.93?±?0.12?μg/mL (columbamine), 3.50?±?0.15?μg/mL (jatrorrhizine), 2.51?±?0.12?μg/mL (berberine), and 1.52?±?0.13?μg/mL (palmatine). A synergy study of these AChEIs was subsequently investigated. In comparison with the IC₅₀ value of M. bealei extract (IC₅₀=0.83?±?0.21?μg/mL), it can be stated that M. bealei extract is much more active than any single AChEI. Thereafter, the determination of these four alkaloids were investigated and AChE inhibitory effect were compared in terms of the extract and corresponding contents of these four alkaloids. The inhibitory effects of extract at each concentration were stronger than four alkaloids mixture. The results demonstrated that not the four AChEI mixture cause the synergistic effect but rather than the concentrations or ratios of these AChEIs play a vital role in their synergy study.     

Novel coumarin derivatives containing 1,2,4-triazole, 4,5-dicyanoimidazole and purine moieties: synthesis and evaluation of their cytostatic activity

We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3-6), 4,5-dicyanoimidazole (compound 7), and purine (compounds 8-13) coumarin derivatives and their acyclic nucleoside analogues 14-18. Structures of novel compounds 3-18 were deduced from their ¹H- and ¹³C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC₅₀ = 35 μM), whereas compound 10 showed moderate activity against the HeLa (IC₅₀ = 33 μM), HepG2 (IC₅₀ = 25 μM) and SW620 (IC₅₀ = 35 μM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.