Antiproliferative steroidal glycosides from Digitalis ciliata

Two new compounds, a furostanol glycoside (1) and a pregnane glycoside (4), along with eight known compounds, belonging to the classes of spirostane (2,3), pregnane (5–7) and cardenolide (8–10) glycosides, were isolated from the seeds of Digitalis ciliata. Their structures were elucidated by 1D and 2D-NMR experiments as well as ESI-MS analysis. For the first time pregnane glycosides of the diginigenin series have been isolated from D. ciliata. The cytotoxic effects of compounds 1–10 on cell viability of several cancer cell lines, namely human breast cancer (MCF-7), human glioblastoma (T98G), human lung adenocarcinoma (A549), human colon carcinoma (HT-29), and human prostate cancer (PC-3) cell lines were evaluated. Compounds 1, 4, 7 and 8 showed antiproliferative effects against MCF-7, HT-29 and A549 cancer cells with IC₅₀ values ranging from 8.3 to 20 μM. The effects of compounds 1–10 on cell proliferation were evaluated on these three cancer cell lines by cell cycle analysis of DNA content using flow cytometry. Compounds 7, 8 and 10 induced significant changes in G₂/M cell cycle phase of all analyzed cells. The obtained results indicate that compounds 7, 8 and 10 are cytostatic compounds effective in reducing cell proliferation by inducing accumulation of the cells in the G₂/M phase of the cell cycle.     

Sesquiterpenes and acetogenins from the marine red alga Laurencia okamurai

Three new halogenated sesquiterpenes, 10-bromo-7α,8α-expoxychamigr-1-en-3-ol (1), 10-bromo-β-chamigren-8-ol (2), and 10-bromo-3-chlorocupar-5-en-2-ol (3), one new C₁₂-acetogenin, desepilaurallene (7), one new naturally occurring sesquiterpene, 7-hydroxylaurene acetate (4), two known sesquiterpenes, allolaurinterol acetate (5) and laurene (6), and one known C₁₅-acetogenin, epilaurallene (8), were isolated from the marine red alga Laurencia okamurai collected from the coast of Rongcheng, China. The structures of these compounds were unambiguously established by 1D, 2D NMR and mass spectroscopic techniques. The bioassay results showed that 4, 5 exhibited potent antibacterial activity, and 1, 4, 5 were toxic to brine shrimp.     

neo-Clerodane diterpenes from Ajuga decumbens and their inhibitory activities on LPS-induced NO production

A phytochemical investigation of the whole plants of Ajuga decumbens led to the isolation of three new (1, 2a, and 2b) and three known (3a−3c) neo-clerodane diterpenes. Their structures were elucidated by spectroscopic data analysis (IR, ESIMS, HR-ESIMS, 1D and 2D NMR), and the structure of 1 was confirmed by X-ray crystallography. The inhibitory activities on LPS-induced NO production of the six diterpenes were evaluated and compounds 2a, 2b, and 3a showed inhibitory effects.     

New icetexane diterpenes with intestinal α-glucosidase inhibitory and free-radical scavenging activity isolated from Premna tomentosa roots

New icetexane diterpenes (1-2); 8, 11, 13-icetexatriene-10-hydroxy, 11, 12, 16-tri acetoxyl (1) and 8, 11, 13-icetexatriene-7, 10, 11-dihydroxy-12, 13-dihydrofuran (2) along with six known compounds namely acetoxy syranzaldehyde (3), syranzaldehyde (4), coniferaldehyde (5), lupeol (6), betulin (7), and 4-(4-methoxy phenyl)-2-butanone (8) were isolated from the roots of Premna tomentosa. The structures of compounds 1 and 2 were established by detailed spectral analysis using UV, IR, ¹H NMR, ¹³C NMR, 1D, 2D and Mass. The newly isolated compounds were screened for rat intestinal α-glucosidase inhibitory and free radical (DPPH) scavenging potentiality. The new icetexane diterpenes (1, 2) and compound 3 were found to have significant α-glucosidase inhibitory and also free radical scavenging (DPPH) activities.     

Neuroprotective bakkenolides from the roots of Valeriana jatamansi

Two new bakkenolides, valerilactones A (1), and B (2), and two known analogues, bakkenolide-H (3) and bakkenolide-B (4), were isolated from the roots of Valeriana jatamansi. Their structures and relative configurations were elucidated by spectroscopic methods (IR, ESIMS, HRESIMS, 1D and 2D NMR) and by comparison of their NMR data with those of related compounds. Compounds 1, 2, and 3 exhibited potent neuroprotective effects against MPP⁺-induced neuronal cell death in human dopaminergic neuroblastoma SH-SY5Y cells.     

Antioxidant flavonoids from the seed of Oroxylum indicum

Three new flavonoid glycosides (1-3) and nineteen known compounds (4-22) were isolated from the aqueous ethanolic extract of the seed of Oroxylum indicum. The structures of 1-3 were elucidated on the basis of spectroscopic analysis. Antioxidant activities of all the isolated compounds were evaluated using a DPPH and an ORAC assay. Compounds 3, 5-7, 9 and 12 exhibited potent antioxidant activity in the DPPH assay, while compounds 3-15 showed potent antioxidant capacity in the ORAC assay, and seven antioxidant flavonoids (4-6, 8, 9, 11, 12) were detected as the main ingredients in the methanolic extract of seed of O. indicum using an HPLC analysis.     

Triterpenes and steroids from the roots of Scorzonera austriaca

A new D:B-friedoolean-type triterpene, 3β-acetoxyglutin-5(10)-en-6-oxo (1), together with seventeen known compounds (2-18) was isolated from the roots of Scorzonera austriaca. Their structures were elucidated mainly by NMR and HR-ESI-MS, as well as on comparison with the reported data. Cytotoxicities of compounds 2, 4, 6, 10-14 and 16 against selected cancer cells of human promyelocytic leukemia (HL-60) and human hepatoma (BEL-7404) were measured in vitro.     

New flavane gallates isolated from the leaves of Plicosepalus curviflorus and their hypoglycemic activity

Two new flavane gallates were isolated from the leaves of Plicosepalus curviflorus. The structure of the new compounds was established as 2S,3R-3,3′,4′,5,7-pentahydroxyflavane-5-O-gallate (1) and 2S,3R-3,3′,4′,5,5′,7-hexahydroxyflavane-4′,5-di-O-gallate (2), respectively. In addition, seven known compounds (−)-catechin (3), quercetin (4), lupeol (5), β-sitosterol (6), pomolic acid (7), β-sitosterol 3-O-β-d-glucopyranoside (8) and 4-methoxycinnamic acid (9) were reported for the first time from the genus Plicosepalus. Compounds 1, 2 and 3 were investigated for their hypoglycemic activity and showed significant hypoglycemic activity in Swiss Albino mice.     

Trichalasins C and D from the plant endophytic fungus Trichoderma gamsii

Two new cytochalasans, trichalasins C (1) and D (2) together with known cytochalasans aspochalasins D (3), M (4) and P (5) were isolated from one endophytic fungus Trichoderma gamsii inhabiting in traditional medicinal plant Panax notoginseng (BurK.) F.H.Chen. The structures for the new compounds 1 and 2 were determined by NMR and HRESIMS, and their relative configurations were established by analysis of coupling constants and NOESY correlations. Compound 3 displaying inhibitory activity with EC₅₀ value 5.72 μM, whereas the EC₅₀ values for compounds 1, 2 and 4, 5 are more than 40 μM.     

Bioactive phenolics from the fruits of Livistona chinensis

This study investigated the antioxidant and cytotoxic activity of the phenolics isolated from the fruits of Livistona chinensis. Four new compounds, 1-{ω-isoferul[6- (4-hydroxybutyl)pentadecanoic acid]}-glycerol (1), E-[6′-(5″-hydroxypentyl)tricosyl]-4-hydroxy-3-methoxycinnamate (2), 2-(3′-hydroxy-5′-methoxyphenyl)-3-hydroxylmethyl-7-methoxy-2,3-dihydrobenzofuran-5- carboxylic acid (3), 7-hydroxy-5,4′-dimethoxy-2-arylbenzofuran (4), together with eleven known phenolics (5-15), were isolated and identified. Among these compounds, 1-4, 5-O-caffeoylshikimic acid (5), caffeic acid (7), and 3-O-caffeoylshikimic acid (8) showed potent antioxidant activity. 1-5, and 8 showed potent antiproliferative activities with IC₅₀ values among 5-150 μM against HepG2 human liver cancer, HL-60 human myeloid leukemia, K562 human myeloid leukemia, and CNE-1 human nasopharyngeal carcinoma cell lines. On the basis of these findings, it could be proposed that the fruits of L. chinensis may serve as attractive mines of powerful anticancer and antioxidant agents for various purposes.     

Monoterpenoid inhibitors of NO production from Paeonia suffruticosa

Three pairs of monoterpene glycosides (1–6), of which compounds 1, 3, and 4 as new compounds, together with one new monoterpene (7) were obtained from the ethanol extract of Paeonia suffruticosa Andrews. Their structures were determined on the basis of chemical methods and spectral data. On this basis, the spectral characteristics of three pairs of monoterpene glycosides were also discussed. The inhibitory effects of isolated compounds on nitric oxide (NO) production in lipopolysaccharide-activated macrophages were evaluated, and NO production was suppressed significantly by compounds 4–7.     

New biologically active compounds from Kenyan propolis

From propolis samples from Kenya, two new arylnaphtalene lignans were isolated, tetrahydrojusticidin B 1 and 6-methoxydiphyllin 2, along with four known phenolic compounds 5–8, found for the first time in propolis. The structures of the compounds were elucidated based on their spectral properties. The geranylstilbenes 7 and 8 demonstrated antibacterial activity against S. aureus, and the geranylflavon macarangin 6 possessed antiradical activity against DPPH radicals.     

Occurrence of stilbene oligomers in Cyperus rhizomes

Investigation of the chemical constituents of Rhizoma Cyperi (Cyperus rotundus Linneus) resulted in the isolation of novel enantiomeric and meso-stilbene trimers [i.e., (+)- and (−)-(E)-cyperusphenol A (1, 2 respectively) and (E)-mesocyperusphenol A (3)], a trimer bearing a novel hexacyclic ring system [cyperusphenol B (5)], as well as known stilbenoids (cyperusphenols C (4) and D (6), scirpusins A (7) and B (8), and piceid (9)) and luteolin. HPLC was used for the optical resolution of 1 and 2 as well as for the identification of cooccurrence of enantiomers of 7. The structures of the isolates were established by spectroscopic analyses, including a detailed NMR spectroscopic investigation. The isolates were evaluated in terms of their antiproliferative activity employing the Jurkat cell line (human T-cell leukemia cells), while the IC₅₀ potencies of a racemate of 1 and 2, 3, 5, and 6 were estimated as 27.4, 40.5, 26.4, and 26.3 μM, respectively. The suppression of cell growth by 6 was due to the induction of apoptosis, which was characterized by nuclear changes and PARP-1 cleavage determined by western blotting. We also evaluated the free radical scavenging activity of the isolates.     

New coumarin glycosides from the leaves of Diospyros crassiflora (Hiern)

Two new 5-methylcoumarin glycosides named diosfeboside A (1) and B (2) and five known compounds namely kaempferol 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranoside (3), ursolic acid (4), betulinic acid (5), stigmasterol (6) and stigmasterol 3-O-β-d-glucopyranoside (7) were isolated from the leaves of Diospyros crassiflora (Hiern). Their structures were established through interpretation of 1 and 2D NMR, mass spectra analysis and comparison with reported data. In vitro cytotoxic activity of the new compounds against human carcinoma cell lines (HL-60, Bel-7402, BGC-823, and KB) was evaluated and no cytotoxicity was observed for each of them.     

N-Methyl-6, 7-dimethoxyisoquinolone in Annona squamosa twigs is the major immune modifier to elicit polarized Th1 immune response in BALB/c mice

Annona squamosa (AS) has traditionally been used as ethnomedicine. We have earlier extracted and fractionated the twigs of AS based upon its bioactivity and observed its immune potentiating activity that was localized in its three fractions. Present communication deals with the phytochemical analysis and pharmacological investigation of the most active chloroform fraction that led to isolation and identification of a number of compounds whose structures were elucidated using 1D and 2D NMR spectroscopic analysis. Amongst the twelve pure compounds isolated, five compounds Lanuginosine (1), (+) -O- methylarmepavine (2), (+)-anomuricine (3), Isocorydine (4), and N-methyl-6, 7-dimethoxyisoquinolone (5) were evaluated in vivo for their immune modifier activities in BALB/c mice after oral administration at three log doses of 0.3, 1.0 and 3.0 mg/kg for 14 consecutive days. Of these, three compounds (1, 2 and 5) showed dose dependent immune stimulating activity. However, the uppermost activity was noted in the compound N-methyl-6, 7-dimethoxyisoquinolone at the 3.0 mg/kg oral dose. The activity was assessed in the form of increased splenic T and B cellular proliferation, up-regulated CD4+, CD8+ and CD19+ cell population and accentuation in the peritoneal macrophage function. The compound possibly acted modifying the expression of Th1- and Th2- cytokines via stimulation of pro-inflammatory Th1 cytokines IL-2 and IFN-γ. These results warrant the use of the above compounds as an efficient immune-stimulant or immune-adjuvant against diseases with immune suppression. The analogs of the compound may further be chemically synthesized to achieve desired immune modifying activity.     

Antiparasitic antioxidant phenylpropanoids and iridoid glycosides from Tecoma mollis

A radical scavenging guided phytochemical study on the stem bark of Tecoma mollis afforded seven active phenylpropanoid glycosides (1–7), including a new one (4), and one iridoid (8). The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds (1–7) displayed promising antioxidant activity (DPPH assay) in relation to ascorbic acid (positive control). The antimicrobial activity for compounds (1–8) was evaluated against five bacterial and five fungal strains. The isolated compounds exhibited nonselective weak to moderate antimicrobial activity. The highest antileishmanial activity against Leishmania donovani was observed for compound (7) with an IC₅₀ value of 6.71 μg/ml, using pentamidine and amphotericin B as drug controls. Compound (5) exhibited moderate antimalarial activity (45% inhibition) against chloroquine sensitive (D6) clones of Plasmodium falciparum.     

Cyclic bisdesmosides from Actinostemma lobatum MAXIM (Cucurbitaceae) and their in vitro cytotoxicity

Two new cyclic bisdesmosides elucidated as lobatoside L (1) and lobatoside M (2) and four known cyclic bisdesmosides (3-6) were isolated from Actinostemma lobatum MAXIM (Cucurbitaceae). Their structures were determined on the basis of spectroscopic analyses including IR, HR-FAB-MS, TOCSY, 1D- and 2D-NMR experiments and chemical reactions. The inhibitory effects of the six compounds on human cancer cell growth (including esophageal squamous carcinoma cell line ECA109, lung cancer cell line A549 and gastric cancer cell line MGC-803) were determined using the MTT assay. The results revealed that the six compounds exhibited cytotoxicity against all the cell lines tested, and compounds 1, 3 and 5 showed significant activities in a dose dependent manner against all the cell lines, especially for compound 1 and 5, the IC₅₀ values for ECA-109 cells were 8.25 μM and 3.71 μM. The results demonstrated that compounds 1 and 5's activities are 2- and 4-fold that of cisplatin.     

Malaysianol B,an oligostilbenoid derivative from Dryobalanops lanceolata

A new oligostilbenoid tetramer, malaysianol B (1), was isolated from the acetone extract of the stem bark of Dryobalanops lanceolata along with seven oligostilbenoids tetramers; hopeaphenol (2), stenophyllol A (3), nepalensinol B (4), vaticanol B (5) and C (6), upunaphenol D (7), and flexuosol A (8). The structures of the isolated compounds were established on the basis of their spectroscopic data evidence. The antibacterial activity of the isolated compounds was evaluated using resazurin microtitre-plate assay.