Antibacterial dihydrobenzopyran and xanthone derivatives from Garcinia cowa stem barks

Two new compounds, garciniacowol (1) and garciniacowone (2) along with 15 known compounds were isolated from the stem barks of Garcinia cowa. Their structures were determined by intensive spectroscopic methods. The structure of 1 was a symmetrical dimeric dihydrobenzopyran derivative, whereas the framework of 2 was a triprenyl caged-xanthone precursor. The antibacterial activities against Escherichia coli TISTR 780, Salmonella typhimurium TISTR 292, Staphylococcus aureus TISTR 1466, and methicillin-resistant S. aureus (MRSA) SK1 of the isolated compounds were also evaluated. Compounds 2 and 9 exhibited good antibacterial activity against MRSA SK1 with the same minimum inhibitory concentration (MIC) value of 2 μg/mL. Moreover, compound 2 also showed good antibacterial activity against S. aureus with an MIC value of 2 μg/mL.     

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.     

Three new antibacterial active diarylheptanoids from Alpinia officinarum

Three new diarylheptanoids, together with ten known ones, were isolated from the ethanol extract from the rhizomes of Alpinia officinarum Hance. The structural identification of these compounds was mainly achieved by spectroscopic methods. The new compounds were elucidated as 7-(4″, 5″-dihydroxy-3″-methoxyphenyl)-1-phenyl -4-heptene-3-one (1), 1, 7-diphenyl-5-heptene-3-one (2) and 4-phenethyl-1, 7-diphenyl -1-heptene-3, 5-dione (3), respectively. All of the compounds showed antibacterial activity against Helicobactor pylori. Especially, the three new compounds showed strong antibacterial activity against Hp-Sydney strain 1 with the MIC values of 9–12 μg/mL, and against Hp-F44 with the MIC values of 25–30 μg/mL.     

Ent-trachyloban-19-oic acid isolated from Iostephane heterophylla as a promising antibacterial agent against Streptococcus mutans biofilms

From the roots of Iostephane heterophylla, six known compounds, namely, ent-trachyloban-19-oic acid (1), the mixture of ent-kaur-16-en-19-oic acid (2) and ent-beyer-15-en-19-oic acid (3), xanthorrhizol (4), 16α-hydroxy-ent-kaurane (5) and 16α-hydroxy-ent-kaur-11-en-19-oic acid (6) were isolated using a bioassay-guided fractionation method. The known compounds (1-6) were identified by comparison of their spectroscopic data with reported values in the literature. In an attempt to increase the resultant antimicrobial activity of 1 and 4, a series of reactions was performed on ent-trachyloban-19-oic acid (1) and xanthorrhizol (4), to obtain derivatives 1a, 1b, and 4a-4d. All the isolated compounds (1-6) and the derivatives 1a, 1b, and 4a-4d were evaluated for their antimicrobial activity against two oral pathogens, Streptococcus mutans and Porphyromonas gingivalis associated with caries and periodontal disease, respectively. Compounds 1, 1b, 2+3, 4 and 4d inhibited the growth of S. mutans with concentrations ranging from 4.1 μg/mL to 70.5 μg/mL. No significant activity was found on P. gingivalis except for 4 with an MIC of 6.8 μg/mL. The ability of 1, 1b, 2+3, 4 and 4d to inhibit biofilm formation by S. mutans was evaluated. It was found that 1, 1b, 4 and 4d interfered with the establishment of S. mutans biofilms, inhibiting their development at 32.5, 125.0, 14.1 and 24.4 μg/mL, respectively.     

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.     

Biologically active steroids from the aerial parts of Vernonia anthelmintica Willd

A new steroid, vernoanthelsterone A (1), and five known steroids were isolated from the aerial parts of Vernonia anthelmintica Willd. Compound 1 possesses a Δ(8(14))-15-one moiety. To our best knowledge, few steroids with this moiety have been reported before. Compounds 1-6 were tested for their antibacterial activities and their effects on estrogen biosynthesis in human ovarian granulosa-like cells (KGN cells). Compound 2 showed the ability to promote estrogen biosynthesis with EC(50) of 56.95 μg/mL and also exhibited the antibacterial activities against Bacillus cereus, Staphyloccocus aureus, Bacillus subtilis and Escherichia coli with MICs ranging from 3.15 to 15.5 μg/mL. The structures of 1-6 were determined on the basis of IR, MS, 1D and 2D NMR.     

Phytochemical and antimicrobial investigations of stilbenoids and flavonoids isolated from three species of Combretaceae

The antimicrobial activity and chemistry of the African Combretaceae has been well studied in recent years. The present study aimed to investigate the phytochemistry and antimicrobial activity of lesser known members of this family viz. C. hereroense, C. apiculatum and C. collinum. Pulverized leaves of C. collinum and C. apiculatum, and the fruit of C. hereroense were extracted with organic solvents and subjected to preparative chromatography. Seventeen phenolic constituents including four phenanthrenes from the fruit of C. hereroense and two known bibenzyls (including a combretastatin) from the leaves of C. collinum were isolated. The compounds were then subsequently tested for their antimicrobial activity against Candida albicans, Mycobacterium fortuitum, Staphylococcus aureus, Escherichia coli and Proteus vulgaris. Pinocembrin showed excellent activity against C. albicans (MIC - 6.25 μg/ml), superior to that of the positive control, fluconazole and against S. aureus (MIC - 12.5 mg/ml). The phenanthrenes (compounds 1, 2, 3 and 5) showed some activity against M. fortuitum and S. aureus with a uniform MIC of 25 μg/ml. From this study it was evident that most stilbenoids and flavonoids from the selected Combretaceae have little or no antimicrobial activity.     

In vitro antifungal activities of longan (Dimocarpus longan Lour.) seed extract

Longan, Dimocarpus longan Lour., contains polyphenolic compounds which exhibit several pharmacological properties. This study aims to evaluate antifungal activities of longan fruit extract in comparison to its active compounds. The results showed that longan seed exhibited antifungal activity against the opportunistic yeasts (Candida species and Cryptococcus neoformans). In contrast, longan pulp and whole fruit did not demonstrate any inhibitory effects. Ellagic acid showed the most potent antifungal activity followed by corilagin and gallic acid, respectively. Ellagic acid inhibited Candida parapsilosis and C. neoformans more effectively than Candida krusei and also some Candida albicans clinical strains. Baidam cultivar possessed higher antifungal activity (MIC=500-4000 μg/ml) as it contained higher contents of ellagic acid and gallic acid than Edor (MIC=1000-8000 μg/ml). For antibacterial activity, only corilagin and gallic acid possessed weak to moderate inhibitory effects against Staphylococcus aureus and Streptococcus mutans, respectively. Longan seed was then applied in the oral care products. Longan effervescent granule (5% extract) significantly reduced adhesion of C. albicans to acrylic strips. Mouthwash containing 0.5% extract exhibited good antifungal activity compared to a commercial product. These findings indicated that longan seed extract and its polyphenolic compounds can be used as an antifungal agent in oral care products for the treatment of opportunistic yeast infection.     

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.     

异长叶烯基噻唑类化合物的合成及其抑菌、抗肿瘤活性研究

以异长烯酮为原料,通过缩合、亲核取代和环化等手段合成了11种新型异长叶烯基噻唑类化合物,同时采用1H NMR、13C NMR、LC-MS和FT-IR对化合物进行了鉴定,从而确定了化合物的结构。对目标化合物进行了抑菌活性实验,结果表明:(E)-4-(4-甲氧基苯基)-2-(2-(1,1,5,5-四甲基-3,4,5,6-四氢-1H-2,4a-亚甲基-7(2H)-亚基)肼基)噻唑(2e)与(E)-4-(4-甲基苯基)-2-(2-(1,1,5,5-四甲基-3,4,5,6-四氢-1H-2,4a-亚甲基-7(2H)-亚基)肼基)噻唑(2g)对细菌(大肠杆菌与金黄色葡萄球菌)具有较好的抑制效果,最低抑菌质量浓度(MIC)为7.8 mg/L。(E)-4-氯苯基-2-(2-(1,1,5,5-四甲基-3,4,5,6-四氢-1H-2,4a-亚甲基-7(2H)-亚基)肼基)噻唑(2b)对真菌(白念球菌与热带假丝酵母)抑制效果优于其他化合物,其MIC值为15.6 mg/L。采用噻唑蓝(MTT)法对目标化合物进行了人体肝癌细胞(HepG 2)抗癌活性测试,化合物2g(IC50=43.9±0.9 mg/L)对HepG 2具有较好的抗癌活性。     

Flavonoids with antiplasmodial and cytotoxic activities of Macaranga triloba

A new flavanone derivative, malaysianone A (1), four prenylated flavanones, 6-prenyl-3'-methoxyeriodictyol (2), nymphaeol B (3), nymphaeol C (4) and 6-farnesyl-3',4',5,7-tetrahydroxyflavanone (5), and two coumarins, 5,7-dihydroxycoumarin (6) and scopoletin (7), were isolated from the dichloromethane extract of the inflorescences of Macaranga triloba. The structures of these compounds were elucidated based on spectroscopic methods including nuclear magnetic resonance (NMR-1D and 2D), UV, IR and mass spectrometry. The cytotoxic activity of the compounds was tested against several cell lines, with 5 inhibiting very strongly the growth of HeLa and HL-60 cells (IC(50): 1.3 μg/ml and 3.3 μg/ml, respectively). Compound 5 also showed strong antiplasmodial activity (IC(50): 0.06 μM).     

Antituberculosis activity of natural and semisynthetic azorellane and mulinane diterpenoids

The antituberculosis activity of 14 natural azorellane and mulinane diterpenoids isolated from Azorella compacta, Azorella madreporica, Mulinum crassifolium, and Laretia acaulis, together with eight semisynthetic derivatives, was evaluated against two Mycobacterium tuberculosis strains. The natural azorellanes azorellanol (3) and 17-acetoxy-13-α-hydroxyazorellane (6), and the semisynthetic mulinanes 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13) and mulinenic acid methyl ester (23), showed the strongest activity, with MIC values of 12.5 μg/mL against both strains. The methylated derivatives 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13), mulin-11,13-dien-20-oic acid methyl ester (15) and mulinenic acid methyl ester (23) proved to be more active than the parent compounds.     

鸭儿芹精油成分、抗氧化与抑菌活性研究

为给鸭儿芹的综合利用提供科学依据,以鸭儿芹茎、叶为原料,采用水蒸气蒸馏法提取鸭儿芹精油,利用气相色谱-质谱联用技术(GC-MS)对鸭儿芹精油成分进行了分析,利用DPPH、ABTS自由基清除能力试验与FRAP试验及打孔法抑菌试验对其精油的抗氧化抗菌活性进行了分析。结果表明:(1)精油成分方面,从鸭儿芹精油中共分离出32个峰,占总离子峰的93.75%,共鉴定出30种化合物,其主要成分分别为α-芹子烯(42.01%)、β-芹子烯(19.86%)、(Z)-β-金合欢烯(12.76%)、镰叶芹醇(4.16%)、α-没药醇(3.93%)等;(2)抗氧化能力方面,当鸭儿芹精油浓度由19μg/m L上升到38μg/m L时,DPPH反应液中Trolox的当量由0.003μmol上升到0.007μmol,ABTS反应液中Trolox的当量由0.069μmol上升到0.074μmol,FRAP反应液中Trolox的当量由0.225μmol上升到0.280μmol,当精油浓度在一定范围内,其DPPH清除能力、ABTS自由基清除能力及铁离子还原抗氧化能力与其浓度间均呈量效关系,且均呈正相关效应,表明鸭儿芹精油具有良好的抗氧化能力;(3)抗菌活性方面,当鸭儿芹精油浓度为1 280 mg/m L时,金黄色葡萄球菌的抑菌圈直径可达7.05 mm,表现出一定的抑菌活性,且其对金黄色葡萄球菌的抑菌效果显著优于其对大肠杆菌的抑菌效果。     

银杏叶聚戊烯醇含氮和含卤素衍生物的抑菌活性研究

利用含氮和含卤素试剂对银杏叶聚戊烯醇末端羟基进行含氮和含卤素的衍生化改性,结果得到5种衍生物,分别为聚戊烯基邻苯二甲酰亚胺(GPH)、氨基聚戊烯醇(GAM)、聚戊烯基季铵盐(GAS)、聚戊烯基三氟乙酰(GTF)和聚戊烯基氯乙酰(GCH),并用~1H NMR分别表征并证实了产物结构。通过比较产物抑菌圈直径和最小抑质量浓度(MIC)来筛选出抗菌作用较强的衍生物,结果显示:GAS对于大肠杆菌和金黄色葡萄球菌的抗菌活性均为最高,其抑菌圈为19.1~19.8 mm,MIC均为31.3 mg/L。同时研究了GAS在亚抑菌质量浓度下(15.6 mg/L)对大肠杆菌和金黄色葡萄球菌的杀菌曲线,结果显示:GAS对大肠杆菌和金黄色葡萄球菌在48 h内具有一定抗菌性;在前8 h内,GAS对于大肠杆菌和金黄色葡萄球菌的杀菌作用较强,致使菌群数量迅速下降;8 h以后,两种菌群都有不同程度的再生,抑菌活性减弱。     

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.     

New antimicrobial pregnane glycosides from the stem of Ecdysanthera rosea

Phytochemical investigation on the stem of Ecdysanthera rosea led to the isolation of eight new C-21 pregnane glycoside ecdysosides A–H (1–8), together with one known pregnane glycoside ecdysantheroside A (9). Their structures were elucidated based on extensive spectroscopic data (MS, IR, 1D and 2D NMR) analysis, as well as comparison with the reported literature data. Antimicrobial activities of all the compounds were evaluated against bacteria and yeasts. Compounds 1, 9, 3 and 5 exhibited moderate antibacterial activities against respective Enterococcus faecalis and Providensia smartii, with MIC value of 12.5 μg/mL. Compound 8 showed significant anti-yeast activity against Cryptococcus neoformans with MIC value of 12.5 μg/mL.     

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).     

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.     

Molluscicidal activity of Aglaia duperreana and the constituents of its twigs and leaves

The methanol (MeOH) extract of the twigs and leaves of Aglaia duperreana was investigated for its molluscicidal activity against Pomacea canaliculata. The extract was found to exhibit significant molluscicidal activity. The ethyl acetate soluble fraction of the extract showed the most potent molluscicidal activity among different solvent fractions. The bioactivity-guided chemical investigation of the ethyl acetate soluble fraction led to a new triterpenoid along with 15 known compounds. Their structures were elucidated by spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance techniques as well as mass spectroscopic analysis. The molluscicidal activities of compounds 2-16 against P. canaliculata were also investigated. Naringenin trimethyl ether showed significant molluscicidal activity with a median lethal concentration (LC(50)) of 3.9 μg/mL, which was indicated higher potency than the positive control, tea saponin (LC(50)=4.5 μg/mL).