Diheteroarylmethyl substituted titanocenes: A novel class of possible anti-cancer drugs

From the reaction of tert-butyl lithium or n-butyl lithium with N-methylpyrrole (1a), furan (1b) or 2-bromo-thiophen (1c), 2-N-methylpyrrolyl lithium (2a), 2-furyl lithium (2b) or 2-thiophenyl lithium (2c), respectively, was obtained. When reacted with 6-(2-N-methylpyrrolyl) fulvene (3a), 6-(2-furyl) fulvene (3b) or 6-(2-thiophenyl) fulvene (3c), the corresponding lithiated intermediates were formed (4a-c). Titanocenes (5a-c) were obtained through transmetallation with titanium tetrachloride. When these titanocenes were tested against pig kidney epithelial (LLC-PK) cells, inhibitory concentrations (IC₅₀) of 32 μM, 140 μM, and 240 μM, respectively, were observed. These values represent improved cytotoxicity against LLC-PK, compared to their ansa-analogues.     

Prenylated C6-C3 compounds with molecular diversity from the roots of Illicium oligandrum

Eleven prenylated C₆-C₃ compounds, illioliganpyranone A (1), illioliganfunone A-D (2-5), and illioliganone D-I (6-11), together with five known prenylated C₆-C₃ compounds (12-16), were isolated from roots of Illicium oligandrum. The structures of 1-11 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and CD experiments. Possible biosynthetic pathways to compounds 1-16 derived from a common precursor of 5-allylbenzene-1,2,4-triol were postulated. All compounds were evaluated for cytotoxic activities against five human cancer cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780). Compound 15 exhibited significant cytotoxicity against HCT-8, BGC-823, A549, and A2780 cell lines with IC₅₀ values of 0.30-2.57 μM. Compound 16 showed moderate selective cytotoxicity against sensitive A2780 cells with IC₅₀ value of 1.38 μM.     

Steroidal alkaloid saponins and steroidal saponins from Solanum surattense

A rare 16β-H steroidal alkaloid saponin (1), an avenacoside-type saponin (2), two steroidal saponins (4, 5), one revised-structure steroidal saponin (3) and six known compounds (6-11) were isolated from aerial parts of Solanum surattense Burm. f. Their structures were established on the basis of physical data, as well as by using spectroscopic (HRESIMS, 1D and 2D NMR), and chemical analysis methods. Compounds 1 and 11 showed cytotoxicity against A549 cell line with IC₅₀ values of 20.3 and 15.7 μM, respectively.     

Unusual stilbenoids and a stilbenolignan from seeds of Syagrus romanzoffiana

Stilbenoids, syagrusins A-B (1-2), and a stilbenolignan, 5-hydroxyaiphanol (3), along with three known phenylpropanoids (4-6), were isolated from seeds of Syagrus romanzoffiana. Compounds 1 and 2 possess unusual 1,4,4a,9a-tetrahydrofluoren-9-one and bicyclo[3.3.0]octanedione skeletons, respectively, whereas compound 3 is a stilbenolignan belonging to a very rare structural class of plant secondary metabolites. Their structures were elucidated by spectroscopic analyses. Compounds 1-3 exhibited moderate inhibitory activity against α-glucosidase with IC₅₀ values of 16.9 μM (1), 23.7 μM (2) and 12.8 μM (3), respectively.     

Steroids from the leaves of Chinese Melia azedarach and their cytotoxic effects on human cancer cell lines

Three new (1-3) and several known (4-6) steroids were isolated from the leaves of Chinese Melia azedarach. The structures of the new compounds were elucidated by means of spectroscopic methods including 2D NMR techniques and mass spectrometry to be (20S)-5,24(28)-ergostadiene-3β,7α,16β,20-tetrol (1), (20S)-5-ergostene-3β,7α,16β,20-tetrol (2), and 2α,3β-dihydro-5-pregnen-16-one (3). The cytotoxicities of the isolated compounds against three human cancer cell lines (A549, H460, U251) were evaluated; only compounds 1, 2, and (20S)-5-stigmastene-3β,7α,20-triol (4) were found to show significant cyctotoxic effects with IC₅₀s from 12.0 to 30.1 μg/mL.     

NF kappa B inhibitors and antitrypanosomal metabolites from endophytic fungus Penicillium sp. isolated from Limonium tubiflorum

Chemical investigation of the endophytic fungus Penicillium sp. isolated from Limonium tubiflorum growing in Egypt afforded four new compounds of polyketide origin, including two macrolides, penilactone (1) and 10,11-epoxycurvularin (2), a dianthrone, neobulgarone G (7), and a sulfinylcoumarin, sulfimarin (14), along with twelve known metabolites (3-6, 8-13, 15 and 16). The structures of all compounds were assigned by comprehensive spectral analysis (1D and 2D NMR) and mass spectrometry. Compounds 3, 4, 13 and 16 showed pronounced antitrypanosomal activity with mean MIC values ranging from 4.96 to 9.75 ??M. Moreover, when tested against a panel of three human tumor cell lines compounds 3, 4, 6 and 12 showed selective growth inhibition against Jurkat and U937 cell lines with IC₅₀ values ranging from 1.8 to 13.3 ??M. The latter compounds also inhibited TNF??-induced NF-??B activity in K562 cells with IC₅₀ values ranging from 1.6 to 10.1 ??M, respectively.     

Methylated anthocyanidin glycosides from flowers of Canna indica

Methylated anthocyanin glycosides were isolated from red Canna indica flower and identified as malvidin 3-O-(6-O-acetyl-β-d-glucopyranoside)-5-O-β-d-glucopyranoside (1), malvidin 3,5-O-β-d-diglucopyranoside (2), cyanidin-3-O-(6″-O-α-rhamnopyranosyl-β-glucopyranoside (3), cyanidin-3-O-(6″-O-α-rhamnopyranosyl)-β-galactopyranoside (4), cyanidin-3-O-β-glucopyranoside (5) and cyanidin-O-β-galactopyranoside (6) by HPLC-PDA. Their structures were subsequently determined on the basis of spectroscopic analyses, that is, ¹H NMR, ¹³C NMR, HMQC, HMBC, ESI-MS, and UV-vis. Compounds (1-4) were found to be in major quantity while compounds (5-6) were in minor quantity.     

Antioxidant activity of a new C-glycosylflavone from the leaves of Ficus microcarpa

By bioactive-guided fractionation of methanol extract of the Ficus microcarpa leaves, one new C-glucosylflavone, ficuflavoside (1), one new megastigmane glycoside, ficumegasoside (8), and twelve known compounds including flavonoids (2-6), phenylpropanoids (7), megastigmanes (9-11) and sterol derivatives (12-14) were isolated. Their chemical structures were elucidated by mass, 1D, and 2D NMR spectroscopies. The antioxidant activities of these compounds were measured using the oxygen radical absorbance capacity methods. Compounds 1-6 exhibited potent antioxidant activities of 6.6-9.5 μM Trolox equivalents at the concentration of 2.0 μM. The results indicated 2, 3, and 5 having meaningful reducing capacity of copper (I) ions concentration of 6.1-8.4 μM.     

Isoprenylated cyclohexanoids from the basidiomycete Hexagonia speciosa

Nine oxygenated cyclohexanoids, speciosins L-T (1-9) as well as a 5H-furan-2-one metabolite, 5′-O-acetylaporpinone A (10), together with known analogs, speciosins A, B, D, E, F, I and K (11-17), and aporpinone A (18), were isolated from a scale-up cultures of the basidiomycete Hexagonia speciosa. Their structures were elucidated by analysis of spectroscopic data, including 1D and 2D NMR. Speciosin B (12) showed significant cytotoxicity against several tumor cell lines with IC₅₀ values in the range 0.23-3.30 μM.     

Anthocyanins in Caprifoliaceae

The qualitative and relative quantitative anthocyanin content of 19 species belonging to the genera Sambucus, Lonicera and Viburnum in the family Caprifoliaceae has been determined. Altogether 12 anthocyanins were identified; the 3-O-glucoside (2), 3-O-galactoside (5), 3-O-(6″-O-arabinosylglucoside) (7), 3-O-(6″-O-rhamnosylglucoside) (9), 3-O-(2″-O-xylosyl-6″-O-rhamnosylglucoside) (10), 3-O-(2″-O-xylosylgalactoside) (11), 3-O-(2″-O-xylosylglucoside) (12), 3-O-(2″-O-xylosylglucoside)-5-O-glucoside (14), 3-O-(2″-O-xylosyl-6″-O-Z-p-coumaroylglucoside)-5-O-glucoside (15) and 3-O-(2″-O-xylosyl-6″-O-E-p-coumaroylglucoside)-5-O-glucoside (16) of cyanidin, in addition to the 3-O-glucosides of pelargonidin and delphinidin (1 and 3). Pigment 7 is the first complete identification of the disaccharide vicianose, 6″-O-α-arabinopyranosyl-β-glucopyranose, linked to an anthocyanidin.     

A new iridoid and effect on the rat aortic vascular smooth muscle cell proliferation of isolated compounds from Buddleja officinalis

A new iridoid, named methylscutelloside (1) together with 19 known compounds belonging to the iridoids (2-4), monoterpenoids (5), flavonoids (6-8), triterpenoids (9-14), and phenylethanoids (15-20) were isolated from the flowers of Buddleja officinalis. Their chemical structures were elucidated on the basis of physicochemical properties, and by spectroscopic methods including 1D, 2D NMR, and MS. All isolated compounds were tested in vitro for their effects on the proliferation of rat aortic vascular smooth muscle cells (VSMCs). Among them, iridoids were the main active components and showed significant inhibitory effects on PDGF-BB-induced proliferation in rat aortic VSMCs.     

Chemical constituents of Picea neoveitchii

Four flavonoids, 5,7,4′-trihydroxy-3,8,-dimethoxy-6-C-methylflavone (1), 5,8,4′-trihydroxy-3,7-dimethoxy-6-C-methylflavone (2), 7-methoxy-6-C-methylkaempferol (3) and kaempferol-7-O-(2″-E-p-coumaroyl)-α-l-arabinofuranoside (4), together with 15 known compounds, were isolated from the twigs and leaves of Picea neoveitchii Mast. Their structures were elucidated on the basis of analyses of spectroscopic data. Compound 4 showed strong anti-fungal activity against Fusarium oxysporum whereas compounds 1-4 were all active against Rhizoctonia solani.     

Non-cannabinoid constituents from a high potency Cannabis sativa variety

Six new non-cannabinoid constituents were isolated from a high potency Cannabis sativa L. variety, namely 5-acetoxy-6-geranyl-3-n-pentyl-1,4-benzoquinone (1), 4,5-dihydroxy-2,3,6-trimethoxy-9,10-dihydrophenanthrene (2), 4-hydroxy-2,3,6,7-tetramethoxy-9,10-dihydrophenanthrene (3), 4,7-dimethoxy-1,2,5-trihydroxyphenanthrene (4), cannflavin C (5) and β-sitosteryl-3-O-β-d-glucopyranoside-2′-O-palmitate (6). In addition, five known compounds, α-cannabispiranol (7), chrysoeriol (8), 6-prenylapigenin (9), cannflavin A (10) and β-acetyl cannabispiranol (11) were identified, with 8 and 9 being reported for the first time from cannabis. Some isolates displayed weak to strong antimicrobial, antileishmanial, antimalarial and anti-oxidant activities. Compounds 2-4 were inactive as analgesics.     

Iridoids from Gentiana loureirii

Iridoid glycosides, 2′,3′,6′-tri-O-acetyl-4′-O-trans-p-(O-β-d-glucopyranosyl)coumaroyl-7-ketologanin (1), 2′-O-caffeoylloganic acid (2), 2′-O-p-hydroxybenzoylloganic acid (3), 2′-O-trans-p-coumaroylloganic acid (4), and 2′-O-cis-p-coumaroylloganic acid (5), were isolated from whole plants of Gentiana loureirii along with six known iridoids, 7-ketologanin (6), loganin (7), loganic acid (8), sweroside, boonein, and isoboonein, and three other known compounds. Their structures were elucidated by spectroscopic means and chemical correlations. The isolated iridoids were evaluated for antibacterial and antioxidant activities, but were either inactive or very weakly active.     

Antineoplastic unsaturated fatty acids from Fijian macroalgae

Phytochemical analysis of Fijian populations of the green alga Tydemania expeditionis led to the isolation of two unsaturated fatty acids, 3(ζ)-hydroxy-octadeca-4(E),6(Z),15(Z)-trienoic acid (1) and 3(ζ)-hydroxy-hexadeca-4(E),6(Z)-dienoic acid (2), along with the known 3(ζ)-hydroxy-octadeca-4(E),6(Z)-dienoic acid (4). Investigations of the red alga Hydrolithon reinboldii led to identification of a glycolipid, lithonoside (3), and five known compounds, 15-tricosenoic acid, hexacosa-5,9-dienoic methyl ester, β-sitosterol, 10(S)-hydroxypheophytin A, and 10(R)-hydroxypheophytin A. The structures of 1-3 were elucidated by spectroscopic methods (1D and 2D NMR spectroscopy and ESI-MS). Compounds 1, 2, and 4, containing conjugated double bonds, demonstrated moderate inhibitory activity against a panel of tumor cell lines (including breast, colon, lung, prostate and ovarian cells) with IC₅₀ values ranging from 1.3 to 14.4 μM. The similar cell selectivity patterns of these three compounds suggest that they might act by a common, but unknown, mechanism of action.     

Osteogenic constituents from Pterospermum acerifolium Willd. flowers

Phytochemical investigation of ethanol extracts of the Pterospermumacerifolium flowers led to the isolation and identification of two new flavones, 4′-(2-methoxy-4-(1,2,3-trihydroxypropyl) phenoxy luteolin (1) and 5,7,3′-trihydroxy-6-O-β-d-glucopyranosyl flavone (2), and one new lactone, 3,5-dihydroxyfuran-2(5H)-one (3) along with 14 known compounds (4-17). The structure of compounds 1-17 was established based on MS, 1D and 2D NMR, spectroscopic analysis. Eight of these compounds (1-6, 8 and 9) were assessed for osteogenic activity by using primary cultures of rat osteoblast. The compounds 1, 3 and 4 significantly stimulated osteoblast differentiation and mineralization as evident from a marked increase in expression of alkaline phosphatase and alizarin red-S staining of osteoblasts.     

New monoterpene glycosides and phenolic compounds from Distylium racemosum and their inhibitory activity against ribonuclease H

Two new monoterpene glycosides, distyloside A-B (1-2), and a new megastigmane glucoside, iso-dihydrodendranthemoside A (3) were isolated from twigs and leaves of Distylium racemosum, along with five known phenolic compounds (4-8). The structures were established via spectroscopic techniques and chemical transformations, and the absolute stereochemistry of 3 was determined by Mosher’s esterification. A homogeneous fluorescence resonance energy transfer (FRET) quenching assay was used to determine the inhibitory activity of isolates (1-8) on the ribonuclease H enzymes from HIV-1, 2, human, and Escherichia coli. Among them, 6″-O-galloylsalidroside (6) showed potent inhibitory effects with an IC₅₀ value of 3.5 μM on HIV-2, and 1.7 μM on human RNase H, respectively.     

Synthesis, structures, luminescence/magnetic properties of complexes of the M/1-hydroxybenzotriazole, M = cobalt, nickel, silver, zinc and copper

Five novel complexes, Co(OBt)₂ · 7H₂O (1) (OBt = 1-hydroxybenzotriazole ion), Ni₃(OBt)₆ · 6H₂O (2), [Ag(OBt)(HOBt)]_n (3), [Zn(OBt)₂]_n (4) and [Cu₂(OBt)₄ · 3H₂O]_n (5) were synthesized by hydrothermal method and characterized by elemental analysis, IR spectroscopy, TGA, XRPD, and single-crystal X-ray diffraction. The results from single-crystal X-ray diffraction indicate that 1-5 are zero-dimensional (0D), zero-dimensional, one-dimensional (1D), and three-dimensional (3D) frameworks, respectively. In particular, 3 is twin crystal; 4 possesses of double-stranded chains; 5 crystallizes in orthorhombic space group P2₁2₁2₁ with a helical chain in its structure. The luminescence properties and the magnetic properties of the five complexes were investigated.     

Furostanol saponins from the rhizomes of Dioscorea japonica and their effects on NGF induction

The rhizome of Dioscorea japonica is a food and medicinal source known as ‘San Yak’ in Korea. Two new furostanol saponins, coreajaponins A (1) and B (2), together with 10 known compounds (3-12) were isolated from the rhizomes of D. japonica. Their structures were determined by spectroscopic methods, including 1D and 2D NMR techniques, HRMS, and chemical methods. Nerve growth factor (NGF), a crucial factor for neuronal survival and differentiation, can potentially improve neurodegenerative diseases and diabetic polyneuropathy. We evaluated the effects of isolates (1-12) on NGF induction in a C6 rat glioma cell line. Coreajaponin B (2) upregulated NGF content without significant cell toxicity, as did 6, 8, 9, and 11.     

New bufadienolides and C23 steroids from the venom of Bufo bufo gargarizans

Six new bufadienolides (1-6) and two new C₂₃ steroids (7 and 8), together with three known compounds (9-11) were isolated from the venom of Bufo bufo gargarizans. Their structures were elucidated by spectroscopic analysis and single-crystal X-ray diffraction. In vitro cytotoxicities of all compounds were evaluated in A549 cancer cell line. Compounds 2, 3 and 10 showed significant cytotoxic activities.