Antibacterial diterpenes from Calceolaria pinifolia

Two new isopimaranes, 19-methylmalonyloxy-ent-isopimara-8(9),15-diene (5) and 19-malonyloxy-ent-isopimara-8(9),15-diene (6), were isolated using bioassay-guided fractionation of the CH(2)Cl(2)-MeOH (1:1) extract of the aerial part of Calceolaria pinifolia along with eight other diterpenes (1-4, 7-10) and two triterpenes (11, 12). All compounds were assayed against Staphylococcus aureus (SA), methicillin-resistant S. aureus (MRSA), Bacillus subtilis (BS), and Escherichia coli (EC). 4-Epi-dehydroabietinol (2) and ent-isopimara-9(11),15-diene-19-ol (8) were found to be active against MRSA with MIC values of 8 and 2 microgram/mL, respectively. Mechanistic studies of 8 in BS suggested rapid and nonspecific inhibition of uptake and incorporation of radiolabeled precursors into DNA, RNA, and protein consistent with membrane-damaging effects in bacteria. Compound 8 did not afford protection against an acute infection with SA in mice.     

Quercus infectoria: a candidate for the control of methicillin-resistant Staphylococcus aureus infections

Acetone, ethyl acetate, 95% ethanol and aqueous extracts of Quercus infectoria (Q. infectoria) demonstrated significant antibacterial activities against all strains of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). Inhibition zones were in the range 11.75-16.82 mm. Both MRSA and MSSA strains exhibited minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values at 0.13 and 0.13-1.00 mg/mL, respectively. At 2 MIC, the growth of two representative MRSA strains was continually inhibited for at least 20 h. Surviving MRSA cells were not detected within 12-14 h after treatment with the extract at 4 MIC concentration. Staphylococcus aureus ATCC 25923 demonstrated similar results.     

Benzoylphloroglucinol derivatives from Hypericum scabrum

Nine new polyprenylated benzoylphloroglucinol derivatives, hyperibones A-I (1-9), were isolated from the aerial parts of the Uzbekistan medicinal plant Hypericum scabrum. Their structures were determined mainly on the basis of spectroscopic evidence (2D NMR and HRMS). Compounds 1, 2, and 4 showed mild in vitro antibacterial activity against methicillin-resistance Staphylococus aureus (MRSA) and methicillin-sensitive Staphylococus aureus (MSSA).     

Antibacterial iridoid glucosides from Eremostachys laciniata

Eremostachys laciniata (L) Bunge (family: Lamiaceae alt. Labiatae; subfamily: Lamioideae) is one of the 15 endemic Iranian herbs of the genus Eremostachys. A decoction of the roots and flowers of E. laciniata has traditionally been taken orally for the treatment of allergies, headache and liver diseases. Three antibacterial iridoid glucosides, phloyoside I (1), phlomiol (2) and pulchelloside I (3) have been isolated from the rhizomes of this plant. The structures of these compounds were elucidated unequivocally by a series of 1D and 2D NMR analyses. The antibacterial activity and brine shrimp toxicity of these compounds were assessed using the resazurin microtitre assay and the brine shrimp lethality assay, respectively. All three iridoid glycosides 1-3 exhibited from low to moderate levels (MIC = 0.05-0.50 mg/mL) of antibacterial activity. Of these compounds, compound 3 was the most active, and displayed antibacterial activity against 9 of 12 different strains tested. The most noteworthy activity of 3 was against Bacillus cereus, penicillin-resistant Escherichia coli, Proteus mirabilis and Staphylococcus aureus with an MIC value of 0.05 mg/mL.     

Antimicrobial and antiparasitic (+)-trans-hexahydrodibenzopyrans and analogues from Machaerium multiflorum

Machaerium multiflorum yielded two additional new (+)-trans-hexahydrodibenzopyrans (HHDBP's), machaeriol C (1) and machaeriol D (2), and three new 5,6-seco-HHDBP's, machaeridiol A (3), machaeridiol B (4), and machaeridiol C (5). Their structures and stereochemistries were determined by 1D and 2D NMR data, including HMBC, NOESY, and circular dichroism experiments. Machaeriol C (1) demonstrated in vitro antibacterial activity against Staphylococcus aureus (IC(50) 0.65 microg/mL) and methicillin-resistant S. aureus (MRSA) (IC(50) 0.70 microg/mL), while its corresponding 5,6-seco-analogues machaeridiol A (3) and machaeridiol B (4) showed antibacterial activity against S. aureus and MRSA (IC(50) 1.0-2.6 microg/mL) and antifungal activity against Candida albicans (IC(50), 2.0-3.5 microg/mL). In addition, machaeridiol B (4) demonstrated antiparasitic activities against Plasmodium falciparum D6 and W2 clones and Leishmania donavani with IC(50) values of 0.64, 0.22, and 0.9 microg/mL, respectively.     

Bionectins A-C, epidithiodioxopiperazines with anti-MRSA activity, from Bionectra byssicola F120

Three new epidithiodioxopiperazine compounds, bionectins A (1), B (2), and C (3), along with a known compound, verticillin D (4), have been isolated from the mycelium of liquid fermentation cultures of the fungus Bionectra byssicola F120. The structures of compounds 1-3 were assigned on the basis of MS and NMR data. Compounds 1 and 2 incorporate a dioxopiperazine moiety with a disulfide bridge in their molecules, while 3 contains a dioxopiperazine ring with two methylsulfanyl groups. Compounds 1 and 2 exhibited antibacterial activity against S. aureus including methicillin-resistant S. aureus (MRSA) and quinolone-resistant S. aureus (QRSA), with MIC values of 10-30 microg/mL, while 3 showed no antibacterial activity even at 100 microg/mL.     

Antimethicillin‐resistant Staphylococcus aureus (MRSA) activity of ‘pacific propolis’ and isolated prenylflavanones

The need to discover and develop alternative therapies to treat methicillin‐resistant Staphylococcus aureus (MRSA) infections is timely. This study was undertaken to purify and identify some anti‐MRSA constituents from propolis, a natural product from the beehive traditionally used in folk medicine for its antimicrobial properties. A crude extract of propolis originating from the Solomon Islands (‘Pacific propolis’) was screened, using an agar dilution assay, in vitro against 15 MRSA clinical isolates. Results revealed activity worthy of further investigation, and subsequent purification work on this crude extract afforded 23 fractions. Further purification of active fractions led to the isolation of compounds 1–4, characterized upon analysis of their spectroscopic data (1D‐ and 2D‐NMR, MS) and by comparison with the literature, as the prenylflavanones propolin H (1), propolin G (2), propolin D (3), and propolin C (4). This study is the first to report the anti‐MRSA activity of ‘Pacific propolis’ and the presence of prenylflavanones in the propolis sample selected. The anti‐MRSA activity of propolin D (3) (MIC 8–16 mg/L) and propolin C (4) (MIC 8–32 mg/L) is reported for the first time. Copyright © 2010 John Wiley & Sons, Ltd.     

Bioactive carbazole alkaloids from Clausena wallichii roots

Four new carbazole alkaloids, clausenawallines C-F (1-4), along with 18 known compounds (5-22) were isolated from the roots of Clausena wallichii. Compounds 3, 9, and 22 exhibited significant antibacterial activity against methicillin-resistant Staphylococcus aureus SK1 (MRSA SK1) and Staph. aureus TISTR 1466 with MIC values in the range 4-16 μg/mL, whereas compound 4 showed the highest cytotoxicity against oral cavity cancer (KB) and small-cell lung cancer (NCI-H187) with IC(50) values of 10.2 and 4.5 μM, respectively.     

In vitro antibacterial effects of Cinnamomum extracts on common bacteria found in wound infections with emphasis on methicillin-resistant Staphylococcus aureus

Ethnopharmacological relevance

Cinnamomum species have been widely used in many traditional systems of medicine around the world. In the Malaysian traditional system of medicine, the leaves, stem bark and stem wood of Cinnamomum iners, Cinnamomum porrectum, Cinnamomum altissimum and Cinnamomum impressicostatum have been used to treat wound infections. To study the antibacterial effects of Cinnamomum iners, Cinnamomum porrectum, Cinnamomum altissimum and Cinnamomum impressicostatum against common bacteria found in wound infections with primary focus on methicillin-resistant Staphylococcus aureus (MRSA).

Materials and methods

The crude extracts from the leaves, stem-bark and stem-wood of Cinnamomum iners, Cinnamomum porrectum, Cinnamomum altissimum and Cinnamomum impressicostatum were obtained using sequential extraction with hexane, ethylacetate, methanol and water. The volatile oils were obtained by hydro-distillation. The antibacterial activities of extracts were investigated using disk diffusion assays and broth microdilution assays.

Results

The volatile oils obtained from the stem-bark of Cinnamomum altissimum, Cinnamomum porrectum and Cinnamomum impressicostatum have shown significant antibacterial activity against a wide range of Gram positive and Gram negative bacteria including MRSA. A few test extracts have shown better activity against MRSA as compared to methicillin sensitive Staphylococcus aureus (MSSA). Amongst all the test extracts, Cinnamomum impressicostatum stem-bark water extract produced the largest inhibition zone of 21.0 mm against MRSA while its inhibition zone against MSSA was only 8.5 mm. The minimum inhibitory concentration (MIC) of this extract against MRSA was 19.5 μg mL⁻¹ and the corresponding minimum bactericidal concentration (MBC) was 39.0 μg mL⁻¹.

Conclusions

This study has scientifically validated the traditional use of Cinnamomum species in treating wound infections. Of high scientific interest was the observation that the antibacterial effect of Cinnamomum impressicostatum stem-bark crude water extract against MRSA was significantly higher than its effect against MSSA, suggesting that the extract contains a compound(s) with higher specific neutralising activity against the drug resistance markers of MRSA.     

Phytochemical studies on Stemona aphylla: isolation of a new stemofoline alkaloid and six new stemofurans

A new stemofoline alkaloid, (2'S)-hydroxy-(11S,12R)-dihydrostemofoline (3), new stemofurans M-R (8-13), and known compounds stemofoline (1), (2'S)-hydroxystemofoline (2), stemofuran E (4), stemofuran F (5), stemofuran J (6), and stilbostemin F (7) have been isolated from the root extracts of Stemona aphylla. The structures and relative configurations of these new compounds have been determined by spectroscopic data interpretation and from semisynthetic studies. These natural and semisynthetic alkaloids were tested for acetylcholinesterase inhibitory activities and were found to be 10-20 times less active than 1',2'-didehydrostemofoline itself. Stemofurans 4, 6, 8, 11, and 13 were tested for their antibacterial and antifungal activities. Three of these showed antibacterial activities against MRSA with MIC values of 15.6 μg/mL.     

Iridoid glucosides and p-coumaroyl iridoids from Viburnum luzonicum and their cytotoxicity

Four new iridoids glucosides (1-4) and seven new iridoid aglycons (5-11) bearing (E)- or (Z)-p-coumaroyl groups were isolated from a methanol extract of the dried leaves of Viburnum luzonicum collected in Kaoshiung, Taiwan. The structures of the new compounds, named luzonoside A (1), luzonoside B (2), luzonoside C (3), luzonoside D (4), luzonoid A (5), luzonoid B (6), luzonoid C (7), luzonoid D (8), luzonoid E (9), luzonoid F (10), and luzonoid G (11), were elucidated by analysis of spectroscopic data and comparison with values for previously known analogues. Among the iridoids isolated in the present study, glucosides 1 and 2, and their aglycons 5-9, exhibited moderate inhibitory activity against HeLa S3 cancer cells, whereas 3 and 4 showed no cytotoxicity even at 100 microM.     

Trigoflavidols A-C, degraded diterpenoids with antimicrobial activity, from Trigonostemon flavidus

Trigoflavidols A (1) and B (2), tetranorditerpenoid dimers possessing a rearrangement skeleton with a spiroketal core moiety, and trigoflavidol C (3), a hexanorditerpenoid, have been isolated from Trigonostemon flavidus along with two known compounds. Compounds 1 and 2 showed moderate antimicrobial activities (MIC values: 3.12-6.25 μg/mL) against Staphylococcus aureus, 8(#)MRSA, and 82(#)MRSA, and 1, 2, and 5 showed weak activities (IC(50) values: 3.75-28.99 μM) against various human tumor cell lines.     

五倍子乙醇提取物对金葡菌的体外抗菌研究

目的观察五倍子乙醇提取物对金黄色葡萄球菌(MRSA和MSSA)的体外抗菌活性.方法采用中药抑菌实验方法对五倍子乙醇提取物进行了112株金黄色葡萄球菌的最低抑菌浓度测定.结果五倍子乙醇提取物对84株耐甲氧西林的金黄色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)和28株甲氧西林敏感的金黄色葡萄球菌(methicillin-sensitive staphylococcus aureus,MSSA)的MIC50、MIC90分别为0.315、0.315和0.63、0.315 mg/mL.结论五倍子乙醇提取物对金黄色葡萄球菌(84株MRSA和28株MSSA)具有较强的抑菌活性.     

Steroidal saponins from Smilax medica and their antifungal activity

Three new steroidal saponins (1-3) were isolated from the roots of Smilax medica, together with the known disporoside A (4). The structures of the new compounds were elucidated mainly by extensive spectroscopic analysis (1D and 2D NMR, FABMS, and HRESIMS). Compounds 1, 2, and 4 demonstrated weak antifungal activity against the human pathogenic yeasts Candida albicans, C. glabrata, and C.tropicalis, with MIC values between 12.5 and 50 microg/mL.     

Antibacterial pterocarpans from Erythrina subumbrans

Seven pterocarpans, erybraedin B (1), erybraedin A (2), phaseollin (3), erythrabyssin II (4), erystagallin A (5), erythrabissin-1 (6) and erycristagallin (7), two flavanones, 5-hydroxysophoranone (8) and glabrol (9), and one isoflavone, erysubin F (10), were isolated from the stems of Erythrina subumbrans (Leguminosae). Their structures were identified by means of spectroscopy. This is the first report of the isolation of the non-alkaloidal compounds from Erythrina subumbrans and the observed dehydration of 6a-hydroxypterocarpans 5 and 6 in CDCl(3) to the corresponding pterocarpenes 11 and 12, respectively. Compounds 8 and 9 were isolated for the first time from the genus Erythrina. Compounds 2 and 4 exhibited the highest degree of activity against Streptococcus strains with an MIC range of 0.78-1.56 microg/ml, whereas compound 7 exhibited the highest degree of activity against Staphylococcus strains, including drug-resistant strains (MRSA and VRSA), with an MIC range of 0.39-1.56 microg/ml. Interestingly, compounds 2, 4, 5 and 7 were more active against several strains of Streptococcus and Staphylococcus than the standard antibiotics vancomycin and oxacillin. Compound 7 showed the highest level of activity against all VRSA strains tested, with an MIC range of 0.39-1.56 microg/ml, which were resistant to both antibiotics. These compounds may prove to be potent phytochemical agents for antibacterial activity, especially against the MRSA and VRSA strains.     

斜叶檀和杠香不同提取物的体外抗菌活性初探

目的探究传统民族药斜叶檀(又称为斜叶黄檀,Dalbergia pinnata(Lour.)Prain)和杠香(又称为滇黔黄檀,Dalbergia yunnanensis Franch)不同提取物的体外抗菌活性。方法采用纸片扩散法探究斜叶檀及杠香的水蒸气蒸馏挥发油、超临界二氧化碳萃取挥发油、水提物及醇提物对金黄色葡萄球菌(Staphylococcus aureus S.aureus)、耐甲氧西林金黄色葡萄球菌(Methicillin Resistant Staphylococcus aureus,MRSA)、粪肠球菌(Enterococcus faecalis)、大肠埃希菌(Escherichia coli)、铜绿假单胞菌(Pseudomonas aeruginosa)及白念珠菌(Candida albicans,C.albicaus)的抑菌效果,并探究提取物浓度对敏感菌株抑菌活性的影响,同时进行最低抑菌浓度(Minimum Inhibitory Concentration,MIC)及最低杀菌浓度(Minimal Bactericidal Concentration,MBC及Minimal Fungicidal Concentration,MFC)的测定。结果两种药物不同的提取物均表现出不同程度的抑菌活性,且活性强弱与提取物浓度成正相关。二者水提物对两种葡萄球菌抑制效果明显,对粪肠球菌抑制效果稍逊;斜叶檀水蒸馏挥发油对白念珠菌抑制效果极强,抑菌圈直径大于30 mm。斜叶檀水蒸馏挥发油对白念珠菌的MIC和MFC均为220μg·mL-1;水提物对两种葡萄球菌的MIC及MBC均为625μg·mL-1。杠香水提物对两种葡萄球菌的抑菌作用均优于其水蒸馏挥发油。结论斜叶檀、杠香的水蒸馏挥发油及水提物有较好的抗菌活性,拥有进一步开发的潜力。     

Chemical composition,antimicrobial activity against Staphylococcus aureus and a pro-apoptotic effect in SGC-7901 of the essential oil from Toona sinensis (A. Juss.) Roem. leaves

Ethnopharmacological relevance

Leaves of Toona sinensis (A. Juss.) Roem. (TSL), a popular vegetable in China, have anti-inflammatory, antidoting, and worm-killing effects and are used in folk medicine for the treatment of enteritis, dysentery, carbuncles, boils, and especially abdominal tumors. Our aim was to investigate the in vitro antimicrobial activity against Staphylococcus aureus and anticancer property of the essential oil from TSL (TSL-EO), especially the pro-apoptotic effect in SGC-7901.

Materials and methods

TSL-EO obtained by hydrodistillation was analyzed by GC/MS and was tested in vitro against twenty clinically isolated strains of Staphylococcus aureus (SA 1–20), which were either methicillin-sensitive Staphylococcus aureus (MSSA) or methicillin-resistant Staphylococcus aureus (MRSA) and two standard strains viz. ATCC 25923 and ATCC 43300. The anticancer activity of TSL-EO was evaluated in vitro against HepG2, SGC7901, and HT29 through MTT assay. Moreover, the apoptosis-inducing activity of TSL-EO in SGC7901 cells was determined by Hoechst 33324 staining and flow cytometry methods. Also, the apoptosis-related proteins viz. Bax, Bcl-2 and caspase-3 were detected by western-blotting.

Results

GC–MS analysis showed that TSL-EO contained a high amount of sesquiterpenes (84.64%), including copaene (8.27%), β-caryophyllene (10.16%), caryophyllene (13.18%) and β-eudesmene (5.06%). TSL-EO inhibited the growth of both MSSA and MRSA, with the lowest MIC values of 0.125 and 1 mg/ml, respectively. Treatment with TSL-EO for 24 h could significantly suppress the viability of three different cancer cell lines (P<0.05). Furthermore, the apoptosis-inducing activity of TSL-EO in SGC7901 cells increased in a dose-dependent manner, potentially resulting from the up-regulated expression of Bax, caspase-3 and down-regulated expression of Bcl-2.

Conclusions

TSL-EO possessed antibacterial activity against Staphylococcus aureus and significant cytotoxicity against cancer cells and particularly prominent pro-apoptotic activity in SGC7901 cells. These bioactivities were probably due to the high content of sesquiterpenes. Our results suggested that TSL-EO possessed potential health benefits and could serve as a promising natural food addictive.     

白及不同提取部位抗耐甲氧西林金黄色葡萄球菌的体内外活性

目的:研究白及对“超级细菌”——耐甲氧西林金黄色葡萄球菌(MRSA)的抑菌作用及活性部位.方法:规范提取白及乙酸乙酯部位、正丁醇部位、萃取后水部位、醇提后水煎液部位等4个部位,采用琼脂平板二倍稀释法测定以上4个部位对金黄色葡萄球菌(MSSA)及MRSA共6株病原菌的MIC;用白及乙酸乙酯部位以两种给药方式对小鼠进行预防给药,测定白及对MRSA感染SPF小鼠的保护力.结果:乙酸乙酯部位和正丁醇部位对受试病原菌均具明显抑菌活性,4个部位中尤以乙酸乙醇部位的抑菌活性最强,其MIC为0.065 ～0.26 g·L-1;且白及乙酸乙酯部位对MRSA感染小鼠有很强的保护作用,其中尤以ip0.5 g·kg-1的保护达到100％.结论:白及对MSSA和MRSA有明显的抑菌作用,乙酸乙酯部位是其主要的活性部位.     

Continentalic acid from Aralia continentalis shows activity against methicillin-resistant Staphylococcus aureus

In a continuing search for compounds with antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), a chloroform extract of roots of Aralia continentalis was found to contain continentalic acid (CA, C(20)H(30)O(2)), a diterpenic acid. This compound exhibited potent activity against standard methicillin-susceptible Staphylococcus aureus (MSSA) as well as clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). It was determined that continentalic acid had minimum inhibitory concentrations (MICs) of approximately 8-16 microg/mL against S. aureus, including the MSSA and MRSA standard strains. Therefore, the results obtained in this study suggest that continentalic acid might have potential as an adjunct in the treatment of antibiotic-resistant bacteria.     

Anti-TB polyynes from the roots of Angelica sinensis

Following chemotaxonomic evidence, the PE and CHCl(3) extracts of the roots of the botanical Angelica sinensis (Oliv.) Diels (Dang Gui) were investigated for in vitro anti-TB activity, in parallel to studying their serotonergic and GABAergic potential. The activities were confirmed to overlap chemically with the neurotropic active principles present in medium lipophilic fractions. Phytochemical investigations led to the isolation of five polyynes: falcarindiol (1), 9Z,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate (2), oplopandiol (3), heptadeca-1-ene-9,10-epoxy-4,6-diyne-3,8-diol (4) and the new polyyne 8-hydroxy-1-methoxy-(Z)-9-heptadecene-4,6-diyn-3-one (5), as characterized by spectroscopic techniques including 1D, 2D NMR and HR-MS. All compounds were tested against two pathogenic strains of Mycobacterium tuberculosis (H37Rv and Erdman) in vitro in a microplate Alamar Blue assay (MABA). The most potent anti-TB constituents were 1 and 2, exhibiting MIC values of 1.4-26.7 microg/mL; 3 showed moderate MICs (49.5 and 50.2 microg/mL, respectively) while 4 and 5 were weakly active (MIC > 60 microg/mL). Notably, none of the five compounds exhibited significant cytotoxicity against Vero cells. These findings not only reveal a new potential area of therapeutic value for A. sinensis, but also underline the role of polyynes as anti-TB active principles in ethnobotanical preparations, and as lead compounds.