Antibacterial prenylbenzoic acid derivatives from Anodendron formicinum

A phytochemical investigation on the stems of Anodendron formicinum led to the isolation of eight prenylbenzoic acid derivatives. Three of these were new compounds, designated as formicinuosides A (1), B (2), and C (3). Their structures were elucidated on the basis of extensive spectroscopic analysis, as well as by comparison with the reported spectroscopic data. This is the first report of chemical constituents from A. formicinum and their antimicrobial activities. Among the isolated compounds, compounds 4, 6 and 8 showed significant antibacterial activities against Providensia smartii with MIC values of 0.781 μg/mL. Moreover, compound 8 showed remarkable antibacterial activity against Escherichia coli with MIC value of 0.781 μg/mL.     

NorA efflux pump inhibitory activity of coumarins from Mesua ferrea

The purpose of this investigation was to study the modulator and efflux pump inhibitor activity of coumarins isolated from Mesua ferrea against clinical strains as well as NorA-over expressed strain of Staphylococcus aureus 1199B. Seven coumarins were tested for modulator activity using ethidium bromide (EtBr) as a substrate. Compounds 1, 4–7 modulated the MIC of EtBr by ≥ 2 fold against wild type clinical strains of S. aureus 1199 and S. aureus 1199B, whereas compounds 4–7 modulated the MIC of EtBr by ≥ 16 fold against MRSA 831. Compounds 1, 4–7 also reduced the MIC of norfloxacin by ≥ 8 fold against S. aureus 1199B, and 4–6 reduced the MIC of norfloxacin by ≥ 8 fold against MRSA 831 at half of their MICs. Inhibition of EtBr efflux by NorA-overproducing S. aureus 1199B and MRSA 831 confirmed the role of compounds 4–6 as NorA efflux pump inhibitors (EPI). Dose-dependent activity at sub-inhibitory concentration (6.25 μg/mL) suggested that compounds 4 and 5 are promising EPI compared to verapamil against 1199B and MRSA 831 strains.     

Quinolone alkaloids with antibacterial and cytotoxic activities from the fruits of Evodia rutaecarpa

Five new quinolone alkaloids, euocarpines A–E (16–20), four new natural products (1, 4, 12, and 14), and eleven known natural products were isolated from the fruits of Evodia rutaecarpa (Juss.) Benth. The structures of the new compounds were elucidated based on spectroscopic evidence. All compounds were evaluated for their antibacterial activity against three strains and for their cytotoxic activity against four human tumor cell lines. The results revealed that 5, 7–11, 13, 14, and 16–20 exhibited moderate antibacterial activities (MIC values: 4–128 μg/mL), and 9, 11, 14, and 17 exhibited moderate cytotoxic activities against HepG-2, Hela, BEL7402, and BEL7403 (IC₅₀ values: 15.85–56.36 μM).     

Antibacterial tetraoxygenated xanthones from the immature fruits of Garcinia cowa

A phytochemical investigation of the acetone extract from the immature fruits of Garcinia cowa led to the isolation of two novel tetraoxygenated xanthones, garcicowanones A (1) and B (2), together with eight known tetraoxygeanted xanthones. Their structures were determined by spectroscopic analysis. All isolated compounds were evaluated for their antibacterial activity against Bacillus cereus TISTR 688, Bacillus subtilis TISTR 008, Micrococcus luteus TISTR 884, Staphylococcus aureus TISTR 1466, Escherichia coli TISTR 780, Pseudomonas aeruginosa TISTR 781, Salmonella typhimurium TISTR 292 and Staphylococcus epidermidis ATCC 12228. α-Mangostin showed potent activity (MIC 0.25–1 μg/mL) against three Gram–positive strains and garcicowanone A and β-mangostin exhibited strong antibacterial activity against B. cereus with the same MIC values of 0.25 μg/mL.     

Synthesis and antimicrobial evaluation of pogostone and its analogues

Pogostone (PO) is one of the secondary metabolites from Pogostemon cablin (Blanco) Benth. (Lamiaceae), serving as the effective component of the antimicrobial activity. In this study, PO and a series of its analogues were synthesized by the reaction of dehydroacetate and aldehydes in tetrahydrofuran under a nitrogen atmosphere. Their activities against Candida albicans, Gram positive bacteria and Gram negative bacteria were evaluated. The antifungal results demonstrated that PO (MIC ranged from 12 to 97 μg/mL against all strains, MFC ranged from 49 to 97 μg/mL against all strains) and A3 (MIC ranged from 12 to 49, MFC over 195 μg/mL) showed a strong activity against Candida albicans. While A1 (MIC ranged from 49 to 97 μg/mL) and A2 (MIC ranged from 24 to 49 μg/mL) have only shown effect against Guangzhou clinical isolates, the antibacterial results demonstrated that PO and its analogues showed no effects against the tested bacteria strains. This study suggests that pogostone analogues, with the appropriated structure modification, represented a kind of promising antifungal agents.     

Lycojaponicuminol A–F: Cytotoxic serratene triterpenoids from Lycopodium japonicum

Six new serratene triterpenoids (1–6), together with nine known triterpenoid compounds were isolated from the extract of club moss Lycopodium japonicum. The structures of isolated compounds were established by spectroscopic methods. The cytotoxic activities of all compounds were evaluated against three human cancer cell lines in vitro by MTT assay. Compounds 2, 6–8 and 11 exhibited moderate activities against all three cell lines with IC₅₀ values of 2.28–11.81 μg/mL.     

New phenyl derivatives from endophytic fungus Aspergillus flavipes AIL8 derived of mangrove plant Acanthus ilicifolius

Two new aromatic butyrolactones, flavipesins A (1) and B (2), two new natural products (3 and 4), and a known phenyl dioxolanone (5) were isolated from marine-derived endophytic fungus Aspergillus flavipes. The structures of compounds 1–5 were elucidated by 1D- and 2D-NMR and MS analysis, the absolute configurations were assigned by optical rotation and CD data, and the stereochemistry of 1 was determined by X-ray crystallography analysis. 1 demonstrated lower MIC values against Staphylococcus aureus (8.0 μg/mL) and Bacillus subtillis (0.25 μg/mL). 1 also showed the unique antibiofilm activity of penetration through the biofilm matrix and kills live bacteria inside mature S. aureus biofilm.     

Cytotoxic sesquiterpenes from Hedychium spicatum: Isolation,structure elucidation and structure–activity relationship studies

Phytochemical investigation of chloroform extract from rhizomes of Hedychium spicatum resulted in the isolation of six new sesquiterpenes (1–6) along with fifteen known compounds (7–21). Their structures were elucidated on the basis of the extensive spectroscopic analyses (IR, Mass and NMR) and by comparison of the data with those reported in the literature. Further, cytotoxic activities of all the isolates were evaluated by determining their inhibitory effects against A-549, B-16, Hela, HT-29, NCI-H460, PC-3, IEC-6 and L-6 cancer cell lines. Results indicated that compounds 1 and 3 may serve as an important natural lead compounds for future development as they showed potent cytotoxic activity against Hela cell lines with an IC₅₀ value of 0.3 μg/mL and 1.80 μg/mL, respectively.     

Four new diterpenoids from the roots of Euphorbia fischeriana

Four new diterpenoids (1,4,5,9), together with 7 known diterpenoids (2,3,6–8,10,11), were isolated from the roots to Euphorbia fischeriana. On the basis of 1D and 2D NMR, HR-ESI-MS spectroscopic analysis, structures of the new compounds were elucidated as 11β-hydroxy-8,14-epoxy-ent-abieta-13(15)-en-16,12-olide (1), 3,20-dihydroxy-ent-1(10), 15-rosadiene (4), 3,7-dihydroxy-ent-1(10), 15-rosadiene (5), ingenol 6,7-epoxy-3- tetradecanoate (9). The compounds isolated were evaluated for their cytotoxicity against four cancer cell lines (A549, BEL7402, HCT116, and MDA-MB-231). Three ingenol diterpenoids (9–11) showed significant cytotoxicity against A549 with IC₅₀ value of 3.35, 2.85, 2.88 μg/mL, respectively.     

Bioactive polyketides and alkaloids from Penicillium citrinum,a fungal endophyte isolated from Ocimum tenuiflorum

Chemical investigation of the endophytic fungus Penicillium citrinum cultured on white beans or on rice led to the isolation of two new alkaloids (1 and 2), along with fourteen known polyketides (6–12, 14–20) and four known alkaloids (3–5, and 13). The structures of the isolated compounds were determined by extensive analysis of the 1D, 2D NMR, and MS data, and by comparison with the literature. Compound 13, which had been previously obtained only by chemical synthesis, was isolated as a natural product for the first time, while compound 6 was firstly reported as a fungal metabolite. A re-isolation of sclerotinin A (14) revealed it to be a diastereoisomeric mixture (14a and 14b), whose stereochemistry was proposed for the first time based on ROESY experiment. All isolated compounds were evaluated for their cytotoxic and antibacterial activities. Compounds 12 and 17 showed significant cytotoxicity against the murine lymphoma cell line L5178Y with IC₅₀ values of 1.0, and 0.78 μg/ml, respectively, while compounds 5, 11, and 15 were moderately active against Staphylococcus aureus ATCC 29213 (MIC 64 μg/ml).     

8-9′ linked neolignans with cytotoxicity from Alpinia conchigera

Five new 8-9′ linked neolignans conchigeranals A–E (1–5), together with three known compounds galanganal (6), galanganols A (7) and B (8), were isolated from the whole plant of Alpinia conchigera. Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Cytotoxicities of compounds 1–8 were tested against two cancer cell lines A549 and Hela. Results showed that 4, 5, 7 and 8 exhibited cytotoxicity against A549 with the IC₅₀ values of 12.36, 9.72, 10.26, 13.05 μg/ml, respectively, and 1–8 against Hela with the IC₅₀ values from 1.53 to 5.29 μg/ml.     

Phytochemical investigation of sesquiterpenes from the fruits of Schisandra chinensis and their cytotoxic activity

Phytochemical investigation of ethanolic extract from the fruits of Schisandra chinensis led to the isolation of four new sesquiterpenes (1–4); their structures were determined by a combination of NMR (1D and 2D) and MS spectroscopic techniques. In addition, all these isolates were screened for their cytotoxic activities against MCF-7, Caco-2, Hela, Lncap, Hep G2 and MDA-MB231 cancer cell lines. Results indicated that compounds 2 and 3 displayed potent cytotoxic activity against Caco2 cell lines with IC₅₀ values of 17.10 μg/mM and 16.46 μg/mM, respectively.     

Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia capillaris

Three new polyacetylenes, 8-(Z)-decene-4, 6-diyne-1, 3, 10-triol (1), 1, 3S, 8S-trihydroxydec-9-en-4, 6-yne (2), 3S, 8S-dihydroxydec-9-en-4, 6-yne 1-O-β -D-glucopyranoside (3), and one new glucosyl caffeoate, 1-O-ethyl-6-O-caffeoyl-β -D-glucopyranose (4), together with 34 known compounds were isolated from Artemisia capillaris. The structures of the new compounds were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRESIMS, [α]_D and CD experiments. Among them, 19 compounds showed activity inhibiting HBsAg secretion; 20 compounds showed activity inhibiting HBeAg secretion; and 25 compounds possessed inhibitory activity against HBV DNA replication according to our anti-HBV assay on HepG 2.2.15 cell line in vitro. The most active compound 12 could inhibit not only the secretions of HBsAg and HBeAg, but also HBV DNA replication with IC₅₀ values of 15.02 μM (SI = 111.3), 9.00 μM (SI = 185.9) and 12.01 μM (SI = 139.2).     

Carapanolides C–I from the seeds of andiroba (Carapa guianensis,Meliaceae)

Five new mexicanolide-type limonoids, carapanolides C–G (1–5), together with two new phragmalin-type limonoids, carapanolides H–I (6, 7), were isolated from the oil of Carapa guianasis AUBLET (Meliaceae) seeds. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR spectra and FABMS. Carapanolides C (1), E (3), and I (7) exhibited moderate activity in the P388 (IC₅₀ 17.9 μM in 1, 15.8 μM in 3) and L1210 cell lines (IC₅₀ 13.3 μM in 1, 18.1 μM in 3, 16.9 μM in 7). On the other hand, Carapanolide D (2) exhibited a strong inhibitory effect in the HL-60 cell line (IC₅₀ 11.0 μM), Carapanolides F (4) showed inhibitory activity in the L1210 cell line (IC₅₀ 15.9 μM), and the cytotoxic activity of Carapanolides I (7) was moderate in all cell lines.     

Anti-neuroinflammatory constituents from Asparagus cochinchinensis

Three new pregnane glycosides, aspacochinosides N (1), O (2), and P (3) were isolated from the roots of Asparagus cochinchinensis, together with four known furostanol glycosides. Their structures were determined by chemical methods and NMR spectral analysis, including extensive 1D and 2D NMR experiments. Compounds 1–7 were evaluated for their anti-neuroinflammatory activity in LPS-induced BV-2 microglial cells. Compounds 2, 3, and 4 showed significant inhibition on NO production in LPS-induced BV-2 microglial cells with IC₅₀ values of 13.51, 4.72, and 63.57 μM, respectively.     

Bioactive cis-stilbenoids from the tubers of Scirpus yagara

Two new cis-stilbenoids, sciryagarol I (1) and II (2) were isolated from the EtOAc extract of the tubers of Scirpus yagara, together with four known compounds. The structures of all compounds were determined by comprehensive analyses of their spectroscopic data and comparison with literature information. The compounds 3, 4 and 6 were isolated for the first time from this genus. Some compounds were tested for their cytotoxicity against human tumor cell lines and antimicrobial activity. Compounds 1–4 showed significant cytotoxicity against the Hela cell lines with IC₅₀ values ranging from 7.21 to 61.21 μM. 1 and 2 exhibited some antimicrobial activity against Staphylococcus aureus and Candida albicans with uniform MICs of 79.3 μl/ml for 2, and 152 μl/ml for 1, respectively.     

Chemical constituents from Aphanamixis grandifolia

Four new terpenoids, nemoralisins D–G (1–4), were isolated from the leaves and stems of Aphanamixis grandifolia, along with two known diterpenoids, nemoralisin C and nemoralisin. Among them, compound 1 is the first example of norsesquiterpenoid with δ-lactone moiety, and nemoralisins E–G (2–4), are a class of acyclic diterpenoids, which are structurally related nemoralisin C and nemoralisin. These structures were established on the basis of spectroscopic methods and the absolute configuration of 1 was determined by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Nemoralisins D–G (1–4) were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines (IC₅₀ > 40 μM), as well as the antimicrobial activities on Staphylococcus aureus, Pseudomonas aeruginosa, MRSA92^# and MRSA98^# (MIC > 50 μg/mL).     

Cytotoxic biflavones from Stellera chamaejasme

Bioassay-guided phytochemical studies on Stellera chamaejasme led to the isolation of two new biflavones, chamaejasmenin E (1) and chamaejasmin D (2), together with ten known compounds. The structures of new compounds were elucidated by extensive spectroscopic analyses and their absolute configurations on 2, 3, 2″ and 3″ were confirmed by TDDFT quantum chemical calculated ECD spectra combined with experimental ECD spectra. All isolated biflavones were evaluated for their cytotoxic activities against Bel-7402 and A549 tumor cell lines, and sikokianin D (3) was found to possess the most potential cytotoxic activities against both the two cell lines with IC₅₀ values of 1.29 ± 0.21 and 0.75 ± 0.25 μM, respectively. Moreover, some structure–function relationships of these bioflavones for cytotoxic activities were explored and summarized.     

A new pentacyclic triterpene with potent antibacterial activity from Limnophila indica Linn. (Druce)

A new pentacyclic triterpenoid constituent, characterized as 3-oxo-olean-12(13),18(19)-dien-29α-carboxylic acid (1) on the basis of detailed spectral studies, was isolated from the aerial parts and roots of Limnophila indica (Scrophulariaceae). Compound 1 exhibited considerable antibacterial activity against three Gram-positive bacteria viz. Bacillus subtilis, Staphylococcus aureus and Listeria monocytogenes (MICs within a range of 25–30 μg/ml) and moderate activity against four Gram-negative bacteria Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginosa, and Pantoea ananatis (MICs within a range of 30–100 μg/ml). The plant pathogenic bacterium P. ananatis and human pathogenic S. typhimurium responded at comparatively higher concentrations of the compound 1, which were 75 and 100 μg/ml respectively. The compound inhibited the growth of Gram-positive B. subtilis and Gram-negative P. aeruginosa completely with a clear bactericidal mode of action at their MIC values. The compound upon treatment on both B. subtilis and P. aeruginosa released substantial amount of nucleic acid in the external medium and also effected the change of morphology towards pleomorphicity, thereby indicating its probable action on cell membrane. Furthermore, the triterpenoid 1 was found not to inhibit a probiotic lactic acid bacterium Lactococcus lactis subsp. lactis LABW4 under in vitro condition and to possess no toxicity in Swiss albino mice.     

Japonicasins A and B,two new isoprenylated flavanones from Sophora japonica

Two new flavanones with a C₁₅ isoprenoid group, japonicasins A and B (1 and 2), were isolated from the leaves of Sophora japonica. This is the first report on the presence of the (2E,7E)-6-isopropyl-3,9-dimethyldeca-2,7,9-trien-1-yl group (C₁₅ isoprenoid group) in isoprenylated flavonoids. Their structures were determined by spectroscopic methods, including UV, IR, 1D and 2D NMR, HRESIMS, and CD experiments. In addition, the antioxidant activities of compounds 1 and 2 were determined through DPPH radical scavenging assays. They exhibited potential antioxidant activities, with IC₅₀ values of 35.1 ± 0.8 μM and 88.7 ± 1.1 μM for compounds 1 and 2, respectively.