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.     

Synthesis, structures and ligating properties of 2,6-bis(phosphino)thiophenol derivatives

New t-butyl-aryl thioethers where the aryl group is 2,6-bis(phosphino)phenyl have been synthesized. The syntheses were completed via sequential ortho-lithiations of t-butylphenylsulfide, followed by chlorophosphine (ClPR₂) quenches; symmetric (2,6-bis(diphenylphosphino)phenyl, (4a)) and unsymmetric (2-diisopropylphosphino-6-diphenylphosphino)phenyl, (4b) aryl groups were obtained. Treatment of 4a with Li or Na naphthalenide yielded 2,6-bis(diphenylphosphino)thiophenol 5. Reactions of 4a or 5 with NiCl₂ · 6H₂O yielded nickel bis(phosphinothiophenolate) 6. Compounds 4a,b, 5 and 6 were characterized by ¹H and ³¹P NMR, and by mass-spectrometry. In addition, 4a, 5 and 6 were characterized by single crystal X-ray diffraction methods.     

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.     

Ecdysteroids from Polypodium vulgare L

Three new compounds (3, 7, and 11) together with eight known phytoecdysteroids (1, 2, 4-6, and 8-10) were isolated from the rhizomes of common polypody, Polypodium vulgare L. The structures of compounds were elucidated by spectroscopic methods including 1D and 2D NMR measurements. The ¹H and ¹³C NMR assignments of compounds 1, 6, 9 and 10 are included.     

Bis-sesquiterpenes and diterpenes from Chloranthus henryi

Bis-sesquiterpenes, henriols A (1), B (2), C (3), and D (4), and three diterpenes, henrilabdanes A (5), B (6), and C (7), together with two known bis-sesquiterpenes and three known labdane diterpenes, were isolated from the ethanol extract of the roots of Chloranthushenryi. Their structures and absolute configurations were elucidated by NMR spectroscopic, X-ray crystallographic and CD analyses. Compounds 1, 5, 6 and 7 showed moderate hepatoprotective activities with IC₅₀ values of 0.19, 0.66, 0.09 and 0.18 μM, respectively. They were not studied further due to the weak effects noted. Compounds 3 and 8 exhibited cytotoxic activities against three types of cancer cell lines including the hepatoma (BEL-7402), human gastric carcinoma (BGC-823), and colon cancer (HCT-8).     

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.     

Anticancer and antifungal activity of copper(II) complexes of quinolin-2(1H)-one-derived Schiff bases

The condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2-14). The copper(II) complexes (2a-14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, ¹H and ¹³C NMR, AAS, UV-Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent anti-Candida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2-8 and 2a-8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G₂. Several derivatives were shown to be active comparable to that of cisplatin.     

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 and transition metal complexes of 3,3-bis(1-vinylimidazol-2-yl)propionic acid, a new N,N,O ligand suitable for copolymerisation

The new N,N,O heteroscorpionate ligand 3,3-bis(1-vinylimidazol-2-yl)propionic acid (Hbvip) (5) was synthesised in five steps starting from 1-vinylimidazole. This ligand is closely related to 3,3-bis(1-methylimidazol-2-yl)propionic acid (Hbmip), but contains two vinyl linker groups which can be used for radical-induced polymerisation reactions. The κ³-N,N,O coordination behaviour of 5 was proven by the synthesis of the tricarbonyl complexes [Re(bvip)(CO)₃] (6), [Mn(bvip)(CO)₃] (7) and [Cu(bvip)₂] (8). To obtain good yields of 6, it was synthesised in water instead of THF. The ligand as well as all three complexes were characterised by X-ray crystallography. Copolymerisation of 5 with pure methyl methacrylate (MMA) or a combination of MMA and ethylene glycol dimethacrylate (EGDMA) led to the solid phases P1 and P2. Polymer-bound rhenium and manganese tricarbonyl complexes could be obtained by the reaction of deprotonated P1 with [MBr(CO)₅] (M = Re, Mn) and also by copolymerisation of 6 and 7 with MMA. In both cases, the facial tripodal binding behaviour was evidenced by IR spectra of the polymers. Furthermore, the content of metal incorporated in the polymers was determined by elemental analysis, AAS or ICP-OES measurements. Reaction of the deprotonated solid phase P1 with copper(II) chloride led to a blue solid-phase (P1-Cu). The UV-Vis absorption maximum of P1-Cu is found at 615 nm, which is almost identical to that found for 8. Thereby, it seems likely that P1 is flexible enough to form bisligand complexes with copper(II). This means that the copper centres act as a kind of crosslinking agents. In contrast, the heterogeneous reaction of P2 with copper(II) chloride yielded a lime green solid phase (P2-Cu). The bathochromic shift of the absorption maximum by 102 nm suggests one-sided bound copper centres.     

Biological evaluation of phenolic constituents from the trunk of Berberis koreana

A bioassay-guided fractionation and chemical investigation of the trunk of Berberis koreana resulted in the isolation and identification of a new sesquilignan, named berbikonol (1), along with fourteen known lignan derivatives (2-15) and a new phenolic compound, named berfussinol (16), together with five known ones (17-21). The structures of these new compounds were elucidated on the basis of 1D and 2D NMR spectroscopic data analysis as well as circular dichroism (CD) spectroscopy studies. Compounds 1-5, 7-8, 11, and 14 showed significant cytotoxicity against the XF498 cell line with IC₅₀ values of 7.14-19.32 μM. In addition, compounds 3-8 and 15 strongly reduced nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, a microglial cell line.     

Three novel coordination networks dependent upon H2btze ligand [H2btze = 1,2-bis(tetrazol-5-yl) ethane]

Three novel metal-organic frameworks, [Zn(btze)]_n (1), [Zn(btze)(H₂O)]_n (2) and [Mn(btze)(H₂O)₄]_n·(H₂O)₂ (3) [btze = 1,2-bis(tetrazol-5-yl) ethane anion], were synthesized and characterized by elemental analysis, IR spectroscopy, X-ray crystallography and thermogravimetric analysis. The crystal structures study reveal that 1 displays a 3D framework, 2 displays a 2D layer structure and 3 displays a 1D polymeric chain. The luminescence properties of 1-3 were investigated at room temperature in solid state.     

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.     

The novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of N-aryl urea: synthesis, anti-inflammatory, antibacterial and antifungal activity evaluation

A series of novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of biological interest were prepared by sequential Bigineli’s reaction, reduction followed by reaction of resulting amines with different arylisocynates. All the synthesized (1-23) compounds were screened against the pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological activity evaluation study reveled that among all the compounds screened, compounds 12 and 17 found to have promising anti-inflammatory activity (68-62% TNF-α and 92-86% IL-6 inhibitory activity at 10 μM). Interestingly compounds 3, 4, 5, 6, 15, 22 and 23 revealed promising antimicrobial activity at MIC of 10-30 μg/mL against selected pathogenic bacteria and fungi.     

β-Diiminatolanthanoid(III) halides revisited

The crystalline compounds [LnCl₂(L)(thf)₂] [Ln = Ce (1), Tb (2), Yb (3)], [NdI₂(L)(thf)₂] (4), [LnCl(L′)₂] [Ln = Tb (5), Yb (6) (a known compound)] and [YbCl(L′′)(μ-Cl)₂Li(OEt₂)₂] (7) have been prepared [L = {N(C₆H₃Prⁱ₂-2,6)C(H)}₂CPh, L′ = {N(SiMe₃)C(Ph)}₂CH, L′′ = {N(SiMe₃)C(C₆H₄Ph-4)}₂CH]. The X-ray molecular structures of 2-7 have been established; in each, the monoanionic ligand L, L′ or L′′ is N,N′-chelating and essentially π-delocalised. Each of 1-7 was prepared from the appropriate LnCl₃, or for 4 [NdI₃(thf)₂], and an equivalent portion of the appropriate alkali metal [Li for 7, Na for 2, 3 and 5, or K for 1, 4 and 6] β-diiminate in thf; the isolation of exclusively 5 and 6 (rather than the L′ analogues of 2 or 3) is noteworthy, as is the structure of 7 which has no precedent in Group 3 or 4f metal β-diiminato chemistry.     

Cinnamate derivatives of fructo-oligosaccharides from Lindelofia stylosa

Phytochemical investigation on the whole plants of Lindelofia stylosa (Kar. and Kir.) has led to the isolation of eight fructo-oligosaccharide cinnamate esters 1-8. Six new compounds 1, 2, and 5-8 were isolated from the butanol extract of the plant. Compounds 1-4 belong to sucrose derivatives, while compounds 5-6 and 7-8 belong to 1-kestose- and nystose-type oligosaccharides, respectively. The fructo-oligosaccharides have been obtained from L. stylosa for the first time.     

Oxygenated verticillene derivatives from Bursera suntui

Medium polarity fractions of the hexane extracts of the stems of Bursera suntui afforded six previously known (1-6) and four hitherto unknown verticillane derivatives: (1S,3Z,7S,8S,11S,12S)-(+)-7,8-epoxyverticill-3-en-12,20-diol (7), (1S,3Z,7S,8S,11S,12S)-(+)-7,8-epoxyverticill-3-en-12,20-diol 20-acetate (8), (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol (9), and (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol 20-acetate (10). Acetylation of 9 and 10 yielded (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol 7,20-diacetate (11), while hydrolysis of 8 gave 7. The structures and stereochemistry of 7-11 were established by spectroscopic analyses, particularly by 1D and 2D NMR spectra and HRESIMS. The conformational preferences of 7-11 were studied by molecular mechanics modelling employing the Monte Carlo protocol followed by B3LYP/DGDZVP DFT calculation, thus supporting the observed ¹H NMR NOESY cross peaks.     

Synthesis of regioisomeric 17β-N-phenylpyrazolyl steroid derivatives and their inhibitory effect on 17α-hydroxylase/C17,20-lyase

The reaction of 3β-hydroxy-21-hydroxymethylidenepregn-5-en-3β-ol-20-one (1) with phenylhydrazine (2a) affords two regioisomers, 17β-(1-phenyl-3-pyrazolyl)androst-3-en-3β-ol (5a) and 17β-(1-phenyl-5-pyrazolyl)androst-5-en-3β-ol (6a). The direction of the ring-closure reactions of 1 with p-substituted phenylhydrazines (2b-e) depends strongly on the electronic features of the substituents. Oppenauer oxidation of 3β-hydroxy-17β-exo-heterocyclic steroids 5a-e and 6a-e yielded the corresponding Δ⁴-3-ketosteroids 9a-e and 10a-e. The inhibitory effects (IC₅₀) of these compounds on rat testicular C_17,20-lyase were investigated by means of an in vitro radioligand incubation technique.     

Phenolic compounds and their anti-oxidative properties and protein kinase inhibition from the Chinese mangrove plant Laguncularia racemosa

Phenolic compounds, named integracin D (1), (7′R, 8′S, 8S)-8-hydroxyisoguaiacin (3), (2R, 3R) pinobanksin-3-caffeoylate (5) and threo-8S-7-methoxysyringylglycerol (6), respectively, were isolated from the Chinese mangrove plant Laguncularia racemosa (L) Gaertn. f. (Combretaceae), together with 23 known phenolic metabolites. Their structures were elucidated on the basis of extensive spectroscopic analyses including that of IR, UV, MS, CD, 1D and 2D NMR spectra as well as by comparison with literature data. Compound 5 showed significant anti-oxidative activity in the DPPH and TEAC free-radical-scavenging assays, while several of the phenolic compounds were tested for protein kinase inhibitory activity in an assay involving 24 different human tumor related protein kinases. Compounds 5, 7, and 23 showed potential inhibition with IC₅₀ values between 2.2 and 3.6 μg/mL toward individual kinases. The ellagic acid derivatives were tested for insecticidal activity.     

Nortriterpenoids and lignans from Schisandra sphenanthera

Nortriterpenoids, sphenadilactone C (1) and sphenasin A (2), together with four known lignans (3-6), were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and compound 2 was further confirmed by single-crystal X-ray diffraction. Compound 1 features a partial enol moiety and an acetamide group in its structure. In addition, compounds 1, 3-6 showed weak anti-HIV-1 activity with EC₅₀ values in the range of 15.5-29.5 μg/mL.     

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.