Cytotoxic lasiodiplodin derivatives from the fungus <Emphasis Type="Italic">Syncephalastrum racemosum</Emphasis>

Chemical investigation of fungal biomass of the fungus Syncephalastrum racemosum led to the isolation of new natural products (3R),(5S)-5-hydroxy-de-O-methyllasiodiplodin (1), 6-oxode-O-methyllasiodiplodin (2), in addition to five known compounds, de-O-methyllasiodiplodin (3), lasiodiplodin (4), (3R),(5R)-5-hydroxy-de-O-methyllasiodiplodin (5), ergosterol (6), and ergosterol peroxide (7). Their structures were elucidated by spectroscopic techniques. The absolute configuration of 1 was determined by a modified Mosher’s method. Compound 1 showed cytotoxicity against cholangiocarcinoma, KKU-M139, KKU-M156, and KKU-M213 cell lines with IC₅₀ values in the range of 14–19 μg/mL, while 3 showed cytotoxicity against KB, BC1, and NCI-H187 cell lines with IC₅₀ values of 12.67, 9.65, and 11.07 μg/mL, respectively.     

Amino and nitro derivatives of 5,7-dimethoxyflavone from <Emphasis Type="Italic">Kaempferia parviflora</Emphasis> and cytotoxicity against KB cell line

Structural modification of 5,7-dimethoxyflavone isolated from Kaempferia parviflora furnished two nitro and seven amino derivatives. Among these, six new (3, 5–6, 8–10) and three known (2, 4, 7) flavonoid derivatives were synthesized. All compounds were evaluated for cytotoxicity against KB cell line using colorimetric method. Compounds 6 and 8 exhibited strong cytotoxicity with IC₅₀ values of 6.80 and 5.84 μg/mL, respectively.     

A new acyclic diterpene acid and bioactive compounds from <Emphasis Type="Italic">Knema glauca</Emphasis>

Investigation of the chemical constituents of the fruits of Knema glauca (Myristicaceae) yielded a new acyclic diterpene acid, named glaucaic acid 4, together with four acylphenols, including 1-(2,6-dihydroxyphenyl) tetradecan-1-one 1, malabaricone A 6, dodecanoylphloroglucinol 7 and 1-(2,4,6-trihydroxyphenyl)-9-phenylnonan-1-one 8, two lignans sesamin 2 and asarinin 3, and a flavan, myristinin D 5. In addition, myristinin A 9 and (±)-7,4′-dihydroxy-3′-methoxyflavan 10 were isolated from its leaves and stems, respectively. When tested against small-cell lung cancer (NCI-H187), epidermoid carcinoma (KB) and breast cancer (BC) cell lines, compounds 1, 6–8 and 10 displayed weak to moderate cytotoxicity. The acylphenols 6–8 displayed antituberculosis activity against the microbe Mycobacterium tuberculosis with MIC values of 25, 50 and 100 μg/mL, respectively, and antiviral activity against herpes simplex virus type 1, with 7 as the most active compound (IC₅₀ = 3.05 μg/mL). Malabaricone A 6 was also active against the malarial parasite Plasmodium falciparum with an IC₅₀ value of 2.78 μg/mL.     

Kaempferol glycosides and cardenolide glycosides,cytotoxic constituents from the seeds of <Emphasis Type="Italic">Draba nemorosa</Emphasis> (Brassicaceae)

Bioassay-directed fractionation of a methanolic extract from the seeds of Draba nemorosa (Brassicaceae) led to isolation of a new flavonol glycoside, drabanemoroside (5, kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranose) along with four known flavonoid derivatives (1–4), four cardenolide glycosides (6–9). Kaempferol glycosides 2 and 5 showed strong cytotoxicity against human small lung cancer cell line A549 and melanoma SK-Mel-2 with an IC₅₀ of 0.5 μg/mL and 1.9 μg/mL, respectively. Cardenolide glycosides 6–9 showed potent cytotoxicity (A549) in the range of 0.01–0.032 μg/mL. Their structures were characterized based on spectroscopic data (2D NMR, HRTOFMS, IR, and UV) and comparison of literature values. The carbohydrate units were also confirmed by comparing the hydrolysate of 5 with authentic monosaccharides.     

Structural modification of 5,7-dimethoxyflavone from <Emphasis Type="Italic">Kaempferia parviflora</Emphasis> and biological activities

5,7-Dimethoxyflavone, a major compound from Kaempferia parviflora, was used as a starting material for structural modification. Seven flavonoid derivatives have been synthesized from this flavone. Two new oxime derivatives 4 and 6 exhibited cytotoxicity against HepG2 cell line with IC₅₀ values of 36.38 and 25.34 μg/mL, respectively, and against T47D cell line with IC₅₀ values of 41.66 and 22.94 μg/mL, respectively. Compound 7 showed cytotoxicity against HepG2 and T47D cell lines with IC₅₀ values of 21.36 and 25.00 μg/mL, respectively. Compounds 6 and 7 showed cytotoxicity nearly equal to the tamoxifen standard. In addition, oxime 6 exhibited antifungal activity against Candida albicans with an IC₅₀ value of 48.98 μg/mL.     

Inhibition of DNA topoisomerases I and II and cytotoxicity of compounds from <Emphasis Type="Italic">Ulmus davidiana</Emphasis> var. <Emphasis Type="Italic">japonica</Emphasis>

Twenty five compounds including ten triterpenes (1–3, 5–11), six flavonoids (12–15, 24, 25), five lignans (17, 18, 21–23), two butenyl clohexnone glycosides (19–20), one fructofuranoside (16) and one fatty acid (4) were isolated from the roots of Ulmus davidiana var. japonica. The structures of those compounds were identified by comparing their physicochemical and spectral data with those of published in literatures. All the compounds were evaluated for DNA topoisomerase inhibitory activities and cytotoxicities. Among the purified compounds, 4 and 19 showed more potent inhibitory acitivities (IC₅₀: 39 and 19 μM, respectively) than camptothecin, as the positive control (IC₅₀: 46 μM) against topoisomerase I. Compounds, 4, 10, 12, 19, 24 and 25 showed strong inhibitory activities toward DNA topoisomerase II (IC₅₀: 0.1, 0.52, 0.47, 0.42, 0.17 μM and 17 nM, respectively), which were more potent than that of etoposide as positive control (IC₅₀: 20 μM). In A549 cell line, 5 and 6 showed cytotoxicities (IC₅₀: 4 μM and 3 μM, respectively, with IC₅₀ of camptothecin as positive control: 10.3 μM). In the HepG2 cell line, 3, 5 and 7 showed cytotoxicity (IC₅₀: 4, 3 and 4 μM, respectively, with IC₅₀ of camptothecin: 0.3 μM). Compounds 6, 12 and 23 showed cytotoxicities in the HT-29 cell line (IC₅₀: 19, 19 and 15 μM, respectively, with IC₅₀ of camptothecin: 2 μM).     

Synthesis and preliminary evaluation of selected 2-aryl-5(6)-nitro- 1<Emphasis Type="Italic">H</Emphasis>-benzimidazole derivatives as potential anticancer agents

In this study we report the synthesis and preliminary evaluation of a series of six 2-aryl-5(6)-nitro-1H-benzimidazole derivatives (1–6) as potential anticancer agents. Cytotoxicity was evaluated against seven human neoplastic cell lines using the MTT assay. Compound 6 [2-(4-chloro-3-nitrophenyl)-5(6)-nitro-1H-benzimidazole] was the most active of the series, showing an IC₅₀ of 28 nM against the A549 cell line. This compound displayed a selective in vitro cytotoxic activity index (>700) in non neoplastic HACAT cells (IC₅₀ = 22.2 μM). Compounds 3 and 6 induce arrest in the S phase of the cell cycle, and compounds 1–6 induce apoptosis in the K562 cell line. Compound 6 induces poly (ADP-ribose) polymerase (PARP) inhibition activity as a potential mechanism of action. These results suggest that compound 6 could be a potent anticancer agent. Compound 3 displayed the best inhibitory activity against PARP with an IC₅₀ value of 0.05 μM, compared to the activity shown by the positive control 3-aminobenzamide (IC₅₀ = 28.5 μM).     

Cytotoxic constituents of<Emphasis Type="Italic">diadema setosum</Emphasis>

5,8-Epidioxycholest-6-en-3-ol (1), cholesterol (2), glycerol 1-palmitate (3) and glycerol 1,3-dioleate-2-stearate (4) were isolated from the methanol extract of the sea urchinDiadema setosum, which was collected from the Halong sea, Vietnam. Chemical structures were established based on extensive 1D, 2D-NMR, FAB-MS, EI-MS spectroscopic data and GC-MS analysis. The NMR spectral data of compound 1 were reassigned by using HMQC and HMBC. Compound1 was found to have strong cytotoxic effect against various cancer cell lines, such as KB (IC₅₀, 2.0 μg/mL), FL (IC₅₀, 3.93 μg/mL), and Hep-2 (IC₅₀, 2.4 μg/mL) byin vitro assay.     

Bile acid derivatives from a sponge-associated bacterium Psychrobacter sp.

In our search for bioactive metabolites from a marine sponge-associated bacterium Psychrobacter sp., a new bile acid derivative (1), which was assumed to be an artifact, were isolated along with six known (2–7) compounds by bioactivity-guided fractionation. Elucidation of the structure of the new compound was done using a combination of NMR (¹H, ¹³C, HMBC, HSQC, and COSY) and MS spectroscopy. Compound 1 exhibited moderate suppressive effects on both NO and IL-6 production at a concentration of 200 μM (87.3 μg/mL) without significant cytotoxicity against cells. Compounds 2–5 and 7 showed selective inhibitory activity against several human pathogenic bacterial strains at the low concentration of 30 μg/well. In a cytotoxicity evaluation, only compound 7 showed mild cytotoxicity against five human solid tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF-498, and HCT-15) with ED₅₀ values in the range of 11–14 μg/mL. These authors equally contributed to this work     

Two new xanthones from the roots of Cratoxylum cochinchinense and their cytotoxicity

Two new xanthones namely cratochinone A (1) and cratochinone B (2), along with 16 known xanthones, were isolated from the roots of Cratoxylum cochinchinense. Their structures were characterized by spectroscopic methods, especially 1D and 2D NMR as well as comparison with those reported in the literature for known xanthones. All isolated compounds were evaluated for their cytotoxicity against five human cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and Hep G2 cell lines). Compounds 2, 5, and 7 showed significant cytotoxic effects against all cell lines with IC₅₀ values in the range of 0.91–9.93 μM, while 10 exhibited cytotoxicity against the KB, HeLa S-3, and HT-29 cells with IC₅₀ values of 7.39, 6.07, and 8.11 μM, respectively. Compound 12 exhibited cytotoxicity against both KB and HeLa S-3 cells with IC₅₀ values of 7.28 and 9.84 μM.

     

Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E<Subscript>2</Subscript> (COX-2) production of flavonoids from seeds of <Emphasis Type="Italic">Prunus tomentosa</Emphasis> Thunberg

Chemical investigation of the 80% Me₂CO extract from the seeds of Prunus tomentosa led to the isolation and identification of six flavonoids: kaempferol (1), kaempferol 3-O-α-L-rhamnopyranoside (2; afzelin), kaempferol 3-O-β-D-(6-acetyl)-glucopyranosyl(1→4)-α-L-rhamnopyranoside (3; multiflorin A), kaempferol 3-O-β-D-glucopyranosyl(1→4)-α-L-rhamnopyranoside (4; multiflorin B), quercetin 3-O-α-L-rhamnopyranoside (5; quercitrin), and quercetin 3-O-β-D-glucopyranosyl (1→4)-α-L-rhamnopyranoside (6; multinoside A). Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E₂ production in interferon-γ (INF-γ) and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro (COX-2) of the isolated compounds were evaluated. Compounds 1, 5, and 6 exhibited potent anti-oxidative activity in the DPPH radical scavenging assay with IC₅₀ values of 57.2, 59.4, and 54.3 μg/mL respectively. The positive control, ascorbic acid, had an IC₅₀ of 55.5 μg/mL. Compounds 1, 5, and 6 also reduced COX-2 levels in a dose dependent manner with IC₅₀ values of 10.2, 8.7, and 9.6 μg/mL respectively, with the positive control, indomethacin, having an IC₅₀ of 5.1 μg/mL. All six compounds inhibited NO production in a dose dependent manner with IC₅₀ values of 35.1, 42.8, 40.0, 44.8, 43.7, and 43.9 μg/mL respectively, while the positive control, L-NMMA, had an IC₅₀ of 42.1 μg/mL.     

Synthesis,antioxidant and antimicrobial evaluation of simple aromatic esters of ferulic acid

Aromatic ester derivatives of ferulic acid where the phenolic hydroxyl is free (6a–d) or acetylated (5a–d) were evaluated for their antioxidant and antimicrobial properties. The superoxide radical scavenging capacity of compounds 5d and 6d–e (IC₅₀ of 0.19, 0.27 and 0.20 mM, respectively) was found to be twice as active as α-tocopherol (IC₅₀ = 0.51 mM). DPPH radical scavenging capacity was moderate and only found in compounds bearing free phenolic hydroxyl groups (6a–e). With regard to antimicrobial properties, compounds 6b and 6c displayed significant activity against Enterococcus faecalis (MICs = 16 μg/mL) and vancomycin-resistant E. faecalis (MIC for 6b, 32 and for 6c, 16 μg/mL). Compound 6c also demonstrated prominent activity against planktonic Staphylococcus aureus with a MIC value of <8 μg/mL and it inhibited bacterial biofilm formation by S. aureus with a MBEC value of <8 μg/mL, which was 64 and 128 times more potent than ofloxacin and vancomycin, respectively.     

Topoisomerase I and II inhibitory constituents from the bark of Tilia amurensis

Two coumarins (1 and 6), one flavan-3-ol (2), one fatty acid (3), and two lignan glycosides (4 and 5) were isolated from the EtOAc and CH₂Cl₂ extract of the bark of Tilia amurensis. Their chemical structures were identified by comparing their physicochemical and spectral data with those of published in literatures. Compounds 4, 5, and 6 were isolated from Tilia genus for the first time. Compounds 2 and 3 showed potent inhibitory activity against both DNA topoisomerase I (IC₅₀ values; 49 μM and 4 μM, respectively, with 18 μM of positive control compound, comptothecin) and DNA topoisomerase II (IC₅₀ values; 13 μM and 3 μM, respectively, with 50 μM of positive control compound, etoposide). However, all compounds did not showed cytotoxicity against the human colon adenocarcinoma cell line (HT-29), the human breast adenocarcinoma cell line (MCF-7), and human liver hepatoblastoma cell line (HepG-2).     

Bioactive metabolites from the sponge-derived fungus <Emphasis Type="Italic">Aspergillus versicolor</Emphasis>

As part of an ongoing search for bioactive metabolites from the fungus Aspergillus versicolor derived from a marine sponge Petrosia sp., an aromatic polyketide derivative (1), two xanthones (2 and 3), and five anthraquinones (4–8) were isolated by bioactivity-guided fractionation. The gross structures were determined based on the NMR and MS spectroscopic data, and the absolute configurations were defined by comparison of optical rotation data with those of reported. Compounds 2, 4, 5, and 7 exhibited significant cytotoxicity against five human solid tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF-498, and HCT-15) with IC50 values in the range of 0.41–4.61 μg/mL. Compounds 4 and 7 exhibited antibacterial activity against several clinically isolated Gram-positive strains with MIC values of 0.78–6.25 μg/mL.     

Cytotoxic 10-(indol-3-yl)-[13]cytochalasans from the fungus <Emphasis Type="Italic">Chaetomium elatum</Emphasis> ChE01

Nine 10-(indol-3-yl)-[13]cytochalasans such as a new chaetoglobosin V (1); two new natural products, prochaetoglobosin III (2) and prochaetoglobosin III_ed (3); six known chaetoglobosins B-D (4–6), F (7), and G (8) and isochaetoglobosin D (9) in addition to two known sterols, 24(R)-5α,8α-epidioxyergosta-6–22-diene-3β-ol (10) and ergosterol (11), were isolated from the fungus Chaetomium elatum ChE01. The structures of these compounds were elucidated by spectroscopic methods. Compounds 1–9 showed cytotoxicity against the human breast cancer (IC₅₀ 2.54–21.29 μM) and cholangiocarcinoma cell lines (IC₅₀ 3.41–86.95 μM).     

A new furostanol saponin from <Emphasis Type="Italic">Asparagus cochinchinensis</Emphasis>

A new furostanol saponin, (25S)-26-O-β-d-glucopyranosyl-5β-furost-20(22)-en-3β, 15β,26-triol-3-O-[α-l-rhamnopyranosyl-(1–4)]-β-d-glucopyranoside, namely, aspacochioside D (1) were isolated from Asparagus cochinchinensis (Lour.) Merr, along with three known saponins, aspacochioside C (2), (25S)-5β-spirostan-3β-yl-O-[O-α-l-rhamnopyranosyl-(1–4)]-β-d-glucopyranoside (3), and pseudoprotoneodioscin (4). The structure of 1 was elucidated on the basis of chemical reactions and spectral analysis (IR, GC, ESI-MS, ¹H-NMR, ¹³C-NMR, DEPT, HMBC, HMQC and NOESY). The antiproliferative effects of 1–4 were evaluated in a cytotoxicity assay against the human tumor cell line, A549. Compound 2 (Aspacochioside C) exhibited moderate cytotoxicity against A-549, with an IC₅₀ value of 3.87 μg/mL.     

A new pyrrole alkaloid isolated from<Emphasis Type="Italic">Arum palaestinum</Emphasis> Boiss. and its biological activities

The phytochemical analysis of the ethyl acetate fraction ofArum palaestinum Boiss. (Araceae) led to the isolation and identification of a new polyhydroxy alkaloid compound; (S)-3,4,5-trihydroxy-1H-pyrrol-2(5H)-one (1), and other five known compounds; caffeic acid (2), isoorientin (3), luteolin (4) and vicenin II (5), as well as the rare compound 3,6,8-trimethoxy, 5,7,3′,4′-tetrahydroxy flavone (6). The structural elucidations of all the compounds were based on spectroscopic data (¹H- and¹³C-NMR, DEPT, HSQC, HMBC and NOE difference techniques) and comparison with literature data. Investigation of the antioxidant activity of the ethyl acetate fraction indicated its strong scavenging capacity for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radicals (SC₅₀ 3.1 ±0.82 μg/mL). Moreover, the treatment of different human cancer cell lines with the ethyl acetate fraction led to dose-dependant suppression in the proliferation of both breast carcinoma cells (MCF-7; IC₅₀ 59.09±4.1 μg/mL) and lymphoblastic leukemia cells (1301; IC₅₀ 53.1±2.9 μg/mL); however, it was found to have no effect on the growth of hepatocellular carcinoma cells (Hep G2).     

Cytotoxic effects of triterpenoid saponins from <Emphasis Type="Italic">Androsace umbellata</Emphasis> against multidrug resistance (MDR) and non-MDR cells

Cytotoxicity-guided fractionation and separation of MeOH extract from Androsace umbellata (Lour.) Merr. led to the isolation of four triterpenoid saponins. Compounds isolated from the n-BuOH soluble fraction were identified as saxifragifolin C (1), A (2), B (3), and D (4) by spectroscopic analysis. Antiproliferative effect of isolated compounds were evaluated by the sulforhodamin B assay against multidrug resistance (MDR; MES-SA/DX5 and HCT15/CLO2) and non-MDR (A549, SK-OV-3, SK-MEL-2, MES-SA, and HCT15) human tumor cell lines. All compounds exhibited strong cytotoxicity against non-MDR human tumor cell lines with IC₅₀ values of 0.19–2.37 μM. MDR cells and non-MDR cells had similar sensitivity to these compounds, however, MDR cells were highly resistant to doxorubicin. Compounds 1–4 induced an increase in the percentage of Annexin V-binding cells, indicating that 1–4 induced apoptosis in RAW 264.7 cells. Also, the condensation of nuclei, a characteristic morphological change of apoptosis, was observed in RAW 264.7 cells by the treatment with n-BuOH fraction, compounds 3 and 4, respectively.     

Triazenoindazoles and triazenopyrazolopyridines: Design,synthesis, and cytotoxic activity

Several triazenoindazoles 3a–e and triazinopyrazolopyridines 6a–i were prepared through the reaction of the corresponding 3-amino-4-chloroindazole and 3-aminopyrazolopyridine diazonium salts 2 and 5 with a number of secondary amines. All compounds were evaluated for their in vitro cytotoxic activity on three cell lines, HepG2, MCF7, and HeLa. Most compounds inhibited cell growth with IC₅₀ less than 0.1 μM. Compound 6d was the most potent, with an IC₅₀ of 0.03 μM against HepG2 and 0.05 μM against MCF7 and HeLa cells.     

Anthraquinones from the Roots of <Emphasis Type="Italic">Knoxia valerianoides</Emphasis> inhibit the formation of advanced glycation end products and rat lens aldose reductase <Emphasis Type="Italic">in vitro</Emphasis>

Eight known compounds, lucidin (1), lucidin-ω-methyl ether (2), rubiadin (3), damnacanthol (4), 1,3,6-trihydroxy-2-methoxymethylanthraquinone (5), 3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (6), 1,3,6-trihydroxy-2-hydroxymethyl-9,10-anthraquinone 3-O-β-primeveroside (7), and vanillic acid (8), were isolated from EtOAc- and n-BuOH-soluble fractions of the roots of Knoxia valerianoides. The structures of 1–8 were identified by analysis of spectroscopic data as well as by comparison with published values. All the isolates were subjected to in vitro bioassays to evaluate advanced glycation end products (AGEs) formation and rat lens aldose reductase (RLAR) inhibitory activity. Compound 5 showed the most potent inhibitory activity (IC₅₀ = 52.72 μM) against AGEs formation. Compounds 1, 2, and 8 also showed potent inhibitory activity on AGEs formation with IC₅₀ values of 79.28, 62.79, and 93.93 μM, respectively, compared with positive control, aminoguanidine (IC₅₀ = 962 μM). While, compounds 1 and 5–7 showed strong inhibitory activity against RLAR with IC₅₀ values of 3.35, 3.04, 6.39, and 2.05 μM, respectively.