Previously undescribed antioxidative azocinyl morpholinone alkaloid from red seaweed Gracilaria opuntia with anti-cyclooxygenase and lipoxygenase properties

In vitro antioxidative and anti-inflammatory bioassay-guided fractionation of the methanol: ethyl acetate crude extract of the thalli of red seaweed Gracilaria opuntia collected from the Gulf of Mannar led to the isolation of a new morpholine alkaloid 3-(2-ethyl-6-((3Z,7Z)-1,2,5,6-tetrahydroazocin-5-yl)hexyl) morpholin-6-one. The substituted azocinyl morpholinone recorded significant 1,1-diphenyl-2-picryl-hydrazil free radical scavenging activities (IC₅₀ ~ 0.086 mg/mL) compared to the commercially available antioxidants, butylated hydroxyanisole, butylated hydroxytoluene, and α-tocopherol (IC₅₀ > 0.20 mg/mL). The title compound showed greater cyclooxygenase-2 (COX-2) inhibitory activity (IC₅₀ 0.84 mg/mL) in conjunction with in vitro 5-lipoxidase inhibitory activity (IC₅₀ 0.85 mg/mL) than non-steroidal anti-inflammatory drugs (NSAIDs). The test compound had better selectivity index (COX-1/COX-2 ratio) (1.17 mg/mL) compared to aspirin (0.02 mg/mL), Na salicylate (0.73 mg/mL) and ibuprofen (0.44 mg/mL). The animals challenged with the substituted azocinyl morpholinone significantly mitigated the carrageenan-induced paw edema in time-dependent manner till the end of 6 h.     

Synthesis and Anticonvulsant Activity of 9-Alkoxy-6,7-dihydro-2H-benzo[c][1,2,4]triazolo[4,3-a]azepin-3[5H]-ones

A series of novel 9-alkoxy-6,7-dihydro-2H-benzo[c][1,2,4]triazolo[4,3-a]azepin-3(5H)-one derivatives was designed and synthesized starting from 2,3,4,5-tetrahydro-7-hydroxy-1H-2-benzazepin-1-one. The structures of these compounds were confirmed by mass, ¹H NMR infrared spectra, and elemental analysis. Their anticonvulsant activity was evaluated by maximal electroshock (MES) test, and their neurotoxic effects were determined by the rotarod neurotoxicity test. The results shown that 3k was the most active compound with median effective dose (ED₅₀) of 27.3 mg/kg, median toxicity dose (TD₅₀) of 118.3 mg/kg, and protective index (PI) of 4.3. Possible structure–activity relationship is discussed.     

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.     

Urease inhibitory profile of extracts and chemical constituents of Pistacia atlantica ssp. cabulica Stocks

The current study was designed to evaluate the urease inhibitory profile of extract and fractions of Pistacia atlantica ssp. cabulica Stocks followed by bioactivity-guided isolated compounds. The crude extract was found significantly active with urease inhibitor (95.40% at 0.2 mg/mL) with IC₅₀ values of 32.0 ± 0.28 μg/mL. Upon fractionation, ethyl acetate fraction displayed 100% urease inhibition with IC₅₀ values of 19.9 ± 0.51 μg/mL at 0.2 mg/mL. However, n-hexane and chloroform fractions exhibited insignificant urease inhibition. Similarly, the isolated compound, transilitin (1) and dihydro luteolin (2) demonstrated marked urease attenuation with 95 and 98% respectively, at 0.15 mg/mL. Both the isolated compounds showed marked potency with IC₅₀ values of 8.54 ± 0.54 and 9.58 ± 2.22 μg/mL, respectively. In short, both the extract and fractions and isolated compounds showed marked urease inhibition and thus a useful natural source of urease inhibition.     

Synthesis,structure, and urease inhibitory activities of Co(III), Mn(II) and Zn(II) complexes with hydrazone derived from protocatechuic acid

[Co^III(L₁)₂·H₂O]NO₃ (1), [Mn^II(L₁)₂·H₂O] (2), and [Zn^II(L₁)₂·H₂O] (3) with a hydrazone derived from protocatechuic acid (HL₁ = C₁₅H₁₃N₃O₃) were designed, synthesized, and characterized by C, H, N elemental analyses, single-crystal X-ray diffraction, and IR spectra, which revealed that the three complexes are similar structures. Docking study has been done. The urease inhibitory activities of the three complexes were tested. Complexes 1 and 3 showed strong inhibitory activity against jack bean urease with IC₅₀ values of 45.9 and 11.64 μM. Complex 2 had no obvious inhibitory activity to urease; the IC₅₀ was > 50 μM.     

Secondary metabolites from marine-derived Streptomyces antibioticus strain H74-21

A new secondary metabolite, (2S,3R)-l-threonine, N-[3-(formylamino)-2-hydroxybenzoyl]-ethyl ester (streptomyceamide C, 1), together with four known compounds 1, 4-dimethyl-3-isopropyl-2,5-piperidinedione (2), cyclo-((S)-Pro-8- hydroxy-(R)-Ile (3), cyclo-((S)-Pro-(R)-Leu (4), and seco-((S)-Pro-(R)-Val) (5), were isolated from the EtOH extract of the fermented mycelium of the marine-derived streptomycete strain H74-21, which was isolated from sea sediment in a mangrove site. The structure of the new compound was established on the basis of its spectroscopic data, including 1D and 2D NMR, HR-TOF-MS. Their antifungal activities against Candida albicans and cytotoxicities against human breast adenocarcinoma cell line MCF-7, human glioblastoma cell line SF-268 and human lung cancer cell line NCI-H460 were tested. Compounds 1 only displayed cytotoxicity against human breast adenocarcinoma cell line MCF-7 with the IC₅₀ value of 27.0 μg/mL. However, compounds 1–5 do not show antifungal activities at the test concentration of 1 mg/mL, and 2–5 have no cytotoxicities at the test concentration of 50 μg/mL.     

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.     

Chemical and biological studies on Bridelia ferruginea grown in Nigeria

Phytochemical investigation of the methanolic extract of dried leaves of Bridelia ferruginea led to the isolation and identification of fourteen compounds (1–14): compound 1 [mixture of palmitic, stearic and oleic acids], stearyl monoester of 2-O-β-?-glucosylglycerol (2), 6β-hydroxy-(20R)-24-ethylcholest-4-en-3-one (3a), 6β-hydroxy-(20R)-24-ethylcholest-4,22-dien-3-one (3b), lutein (4), vomifoliol (5), corilagin (6), kaempferide-3-O-β-?-glucoside (7), myricetin (8), isomericitrin (9), isoquercetin (10), myricitrin (11), quercitrin (12), rutin (13), and β-sitosterol glucoside (14). The total extract exhibited moderate activity towards CB2 receptor and 90% inhibition against leishmanial pathogen Trypanosoma brucei. Compound 4 exhibited 73% displacement in CB2 receptor with IC₅₀ 56.47 μM, and 93% inhibition towards T. brucei with IC₅₀ 4.16 μM. Compound 11 showed 99% inhibition towards Escherichia coli with IC₅₀ 1.123 μM.     

Carbazole-pyranocoumarin conjugate and two carbazole alkaloids from the stems of Clausena excavata

A carbazole-pyranocoumarin conjugate, carbazomarin B (1), and two carbazole alkaloids, 6-methoxymukonidine (2) and 2-hydroxy-3-methoxycarbazole (3), together with 27 known compounds (4–30), were isolated from the stems of Clausena excavata. Their structures have been elucidated by spectroscopic analyses. Compound 2 showed moderate cytotoxicity to HuCCA-1, MOLT-3 and HepG2 cancer cell lines with IC₅₀ values of 15.09–28.50 μg/mL, but none to A549 cell line. Heptaphylline (6) and nordentatin (23) were found to show moderate cytotoxic activity against HepG2 cell line with IC₅₀ values of 12.33 and 11.33, respectively, while clausine K (27) exhibited strong cytotoxicity with IC₅₀ value of 1.05 μg/mL, better than a standard drug (etoposide, IC₅₀ 13.40 μg/mL).     

In vitro antiplasmodial and cytotoxic activities of sesquiterpene lactones from Vernonia fimbrillifera Less. (Asteraceae)

Due to the in vitro antiplasmodial activity of leaf extracts from Vernonia fimbrillifera Less. (Asteraceae), a bioactivity-guided fractionation was carried out. Three sesquiterpene lactones were isolated, namely 8-(4’-hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8α-[4’-hydroxymethacryloyloxy]-4-epi-sonchucarpolide (3). Their structures were elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by comparison with published data. The isolated compounds exhibited antiplasmodial activity with IC₅₀ values ≤ 5 μg/mL. Cytotoxicity of the compounds against a human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was assessed to determine selectivity. Compound 3 displayed promising selective antiplasmodial activity (SI > 10).     

Structures and bioactivities of seven flavonoids from Osmanthus fragrans ‘Jinqiu’ essential oil extraction residues

Osmanthus fragrans are well-known for their fragrance, but it is wasteful if to discard O. fragrans flower after extracting their essential oils. In this paper, we found that O. fragrans flower residues were rich in flavonoids. Six flavonoids and one phenylethanoid glycoside were isolated from the ethanol extract of O. fragrans flower residues, identified as quercetin (1), rutin (2), verbascoside (3), genistin (4), kaempferol (5), isorhamnetin (6) and naringin (7). In bioactivity study, kaempferol (IC₅₀ = 1.43 μg/mL) showed the best anti-inflammatory activity. Isorhamnetin, quercetin, kaempferol, verbascoside and rutin (the values of IC₅₀ were 18.30, 11.05, 16.88, 20.21 and 22.76 μg/mL, respectively) showed excellent DPPH free radical scavenging activity. Verbascoside performed relatively well at inhibiting the growth of both CT26 colonic carcinoma cells (IC₅₀ = 46.87 μg/mL) and HepG2 hepatocarcinoma cells (IC₅₀ = 30.58 μg/mL). In addition, quercetin and kaempferol showed strong anti-proliferation activity against HepG2 cells.     

Phytochemical analysis and antioxidant potential of the leaves of Garcinia travancorica Bedd.

Phytochemical analysis of the leaves of Garcinia travancorica, a hitherto uninvestigated endemic species to the Western Ghats of south India, resulted in isolation and characterisation of the polyisoprenylated benzophenones 7-epi-nemorosone (1) and garcinol (2) along with biflavonoids GB-1a (3), GB-1 (4), GB-2 (5), morelloflavone (6) and morelloflavone-7″-O-β-d-glycoside or fukugiside (7). The compounds were identified using various spectroscopic techniques, mainly through NMR and MS. The methanol extract and the biflavonoids 3, 4, 5 and 7 showed potential in vitro antioxidant activities. The IC₅₀ value of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of compound 7 was 8.34 ± 2.12 μg/mL, comparable to that of standard ascorbic acid (3.2 ± 0.50 μg/mL). In the superoxide radical scavenging assay, compound 7 gave IC₅₀ value of 6.95 ± 1.33 μg/mL close to standard ascorbic acid with IC₅₀ value of 5.8 ± 0.25 μg/mL. Validated HPTLC estimation revealed G. travancorica as a rich source of morelloflavone-7″-O-β-d-glycoside (7.12% dry wt. leaves).     

Structure activity relationship of bergenin,p-hydroxybenzoyl bergenin, 11-O-galloylbergenin as potent antioxidant and urease inhibitor isolated from Bergenia ligulata

Ethanol extract of the aerial parts of Bergenia ligulata was subjected to solvent–solvent separation followed by various chromatographic techniques that lead to isolation of bergenine (1), p-hydroxybenzoyl bergenin (2), 11-O-galloylbergenin (3) and methyl gallate (4) as major constituents. Ethyl acetate fraction showed a dose-dependent urease inhibitory pattern with IC₅₀ value of 54μg/mL. Structures of compounds 1 and 3 were established by XRD and 2, 4 by NMR. All these compounds were subjected to DPPH scavenging activity, reducing power assay and urease inhibitory activity. The EC₅₀ 7.45 ± 0.2 μg/mL and 5.39 ± 0.28 μg/mL values in terms of antioxidant and reducing power, respectively, were less for 3. Compounds 1–3 showed moderate to significant urease inhibitory potential with IC₅₀ 57.1 ± 0.7, IC₅₀ 48.4 ± 0.3 and 38.6 ± 1.5. Antioxidant activities and urease inhibitory potential were investigated and compound 3 was found to be the most active.     

A new naphtho-<Emphasis Type="Italic">γ</Emphasis>-pyrone from mangrove endophytic fungus ZSU-H26

A new naphtho-γ-pyrone, 5-hydroxy-6,8-dimethoxy-2-benzyl-4H-naphtho[2,3-b]-pyran-4-one (1), together with three known compounds 5,7-dihydroxy-2-methylbenzopyran-4-one (2), 3,5-dihydroxy-2,7dimethylbenzopyran-4-one (3) and cyclo(Tyr-Tyr) (4) were isolated from the mangrove endophytic fungus Phomopsis sp. ZSU-H26 obtained from the South China Sea. Their structures were elucidated by spectroscopic methods, mainly 1D and 2D NMR spectroscopic techniques. Primary bioassays showed that 1 exhibited cytotoxicity against HEp-2 and HepG2 cells with IC₅₀ values of 10 and 8 μg/mL, respectively.     

Cytotoxic,antitumour-promoting and inhibition of protein denaturation effects of flavonoids,isolated from Potentilla evestita Th. Wolf

This study was designed to evaluate the isolated flavonoids (chrysin 1, and umbelliferone 2) from Potentilla evestita for cytotoxic, antitumour-promoting and inhibition of protein denaturation activities. The results showed marked cytotoxic effect of compounds 1 and 2 in brine shrimp cytotoxic assay at various concentrations with LD₅₀ of 34.5 and 31.8 mg/mL, respectively. In Epstein–Barr-virus early antigen activation assay, both compounds 1 and 2 illustrated significant antitumour-promoting effect with IC₅₀ values of 462 and 308 mol ratio/32 pmol TPA, respectively. The cytotoxic and antitumour-promoting effects of compounds were strongly supported by inhibition of protein denaturation activity with IC₅₀ of 119 and 112 μg/mL, respectively. In conclusion, both compounds possess strong cytotoxic, antitumour-promoting and inhibition of protein denaturation activities.     

Activity-guided investigation of Carissa carandas (L.) roots for anti-inflammatory constituents

The present study was structured to investigate the anti-inflammatory potential of the extracts, fractions and compounds isolated from Carissa carandas (L.) roots. Bioassay guided fractionation of methanol extract based on inhibitory potential towards proinflammatory mediators (TNF-α, IL-1β and nitric oxide (NO)) led to the identification of stigmasterol (1), lupeol (2), oleanolic acid (3), carissone (4) and scopoletin (5) as potential anti-inflammatory agents. Carissone (4) (IC₅₀ = 20.1 ± 2.69 μg/mL) and scopoletin (5) (IC₅₀ = 24.6 ± 1.36 μg/mL) exhibited significant inhibition of NO production comparable to specific NO inhibitor (L-NAME; IC₅₀ = 19.82 ± 1.64 μg/mL) without affecting the cell viability. Also, 4 and 5 at a concentration of 30 μM were found to inhibit 41.88–53.44% of TNF-α and IL-1β. To the best of our knowledge, this is the first report displaying the anti-inflammatory effects of C. carandas (L.) roots, partially mediated by inhibition of TNF-α, IL-1β and NO.     

Terrenolide S,a new antileishmanial butenolide from the endophytic fungus Aspergillus terreus

Terrenolide S, a new butenolide derivative (6), together with six known compounds: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), stigmasta-4,6,8(14),22-tetraen-3-one (3), terretonin A (4), terretonin (5) and butyrolactone VI (7) have been isolated from the endophytic fungus Aspergillus terreus isolated from the roots of Carthamus lanatus (Asteraceae). Their structures were established by extensive spectroscopic analyses (1D, 2D NMR and HRESIMS), as well as optical rotation measurement and comparison with literature data. Compound 1 displayed a potent activity towards methicillin-resistant Staphylococcus aureus (MRSA) and Cryptococcus neoformans with IC₅₀ values of 2.29 and 10.68 µM, respectively. Moreover, 1, 2 and 6 exhibited antileishmanial activity towards Leishmania donovani with IC₅₀ values of 11.24, 15.32 and 27.27 µM, respectively and IC₉₀ values of 14.68, 40.56 and 167.03 µM, respectively.     

A new lignan glycoside from the aerial parts and cytotoxic investigation of Uvaria rufa

Chemical investigation of the aerial parts of Uvaria rufa (Dunal) Blume collected from Vietnam yielded one new lignan glycoside, ufaside (1), along with six known compounds, oxoanolobine (2), ergosta-4,6,8(14),22-tetraen-3-one (3), catechin (4), epicatechin (5), daucosterol (6) and glutin-5-en-3-one (7). Their chemical structures were determined by using NMR, HR-MS spectroscopic analyses and in comparison with the reported data. A cytotoxic analysis of U. rufa herb extracts was performed for the first time using nine human cancer cell lines (MCF-7, MDA-MB-231, LNCaP, MKN7, SW480, KB, LU-1, HepG2 and HL-60) derived from different tumour types. Of these seven constituents, compounds 2 and 3 displayed moderate cytotoxicity against the human lung adenocarcinoma cell line (LU-1) with IC₅₀ values of 9.22 ± 1.02 μg/mL and 10.21 ± 1.16 μg/mL, respectively.     

Airlanggins A-B,two new isoprenylated benzofuran-3-ones from the stem bark of Calophyllum soulattri

Two new isoprenylated benzofuran 3-ones, airlanggin A (1) and B (2) along with two known xanthones, ananixanthone (3) and trapezifolixanthone (4) were isolated from the stem bark of Calophyllum soulattri. Structures of all the compounds were elucidated using extensive spectroscopic methods, including UV, IR, HRESIMS, 1D and 2D NMR. Compounds 1–4 were evaluated for their cytotoxicity against P-388 cells, showing that compound 3 was the most active with IC₅₀ 0.68 μg/mL and compound 1 showed moderate activity with IC₅₀ 5.80 μg/mL.