Semisynthesis, in silico study and in vitro antibacterial evaluation of fucosterol derivatives.

Thirteen fucosterol derivatives were prepared by structural modification at the hydroxyl group in C-3 and catalytic hydrogenation at the carbon-carbon double bond in C-5(6) and C-24(28). The structures of all compounds were established based on their spectral data (IR, MS, and NMR). Fucosterol (1) and its derivatives (2-12, and a mixture of 13a and 13b) were evaluated for their in vitro antibacterial activity against Klebsiella pneumoniae (ATCC 10031), Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 15442), Streptococcus mutans (ATCC 0046) and Staphylococcus aureus using the microdilution method. Among them, 1, 8, 9, 10, and a mixture of 13a and 13b exhibited the best antibacterial activity. The derivative 7 was inactive against all bacterial strains evaluated (MIC ≥ 2.327 mM). In addition, the investigation of binding interactions of more active compounds (1, 8, 9, 10, and mixture of 13a and 13b) to appropriate proteins was performed using molecular docking. This paper registers for the first time the in silico studies on the antibacterial activity of compounds 1, 8, 9, 10, and mixture of 13a/13b, and the spectral data of compounds 4, 6, and 7.

Chemical constituents and acetylcholinesterase inhibitory activity from the stems of Bauhinia pentandra.

Two steroids (1 and 2), two oxepin derivatives (3 and 4) and seven flavonoids (5-11) were isolated from the stems of Bauhinia pentandra. Their structures were elucidated on the basis of NMR spectroscopic data, and by comparison with data previously reported in the literature. The ethanol extract from the stems of B. pentandra and the compounds, 4, 5, 6, 7, 8 and 11 have been evaluated as acetylcholinesterase inhibitors, and among these, the compound 5 exhibited the strongest activity. In addition, all the isolated compounds are reported for the first time as constituents of B. pentandra.

Chemical composition and biological activities of the essential oils from Vitex-agnus castus, Ocimum campechianum and Ocimum carnosum.

The essential oils obtained by hydrodistillation from fresh leaves of Vitex agnus-castus and Ocimum campechianum, and from fresh inflorescences of Ocimum carnosum were analysed by GC-FID and GC-MS. The major components of V. agnus-castus essential oil were identified as 1,8-cineole (47.9%), terpinyl α-acetate (11.6%), sabinene (11.2%) and caryophyllene oxide (9.7%), while in the O. campechianum essential oil were eugenol (72.1%), ß-elemene (6.8%), (E)-caryophyllene (6.4%) and bicyclogermacrene (5.2%). Linalool (79.0%), α-epi-cadinol (5.4%), terpinen-4-ol (3.2%) and 1,8-cineole (2.8%) were the major constituents in the O. carnosum essential oil. The essential oils were subsequently evaluated for their larvicidal and cytotoxic activities. Larval bioassay against Aedes aegypti of V. agnus-castus, O. campechianum and O. carnosum essential oils showed LC50 values of 97.55 ± 0.35, 81.45 ± 0.35 and 109.49 ± 0.35 µg/mL, respectively. The in vitro cytotoxic activities of the essential oils has been evaluated on breast adenocarcinoma (MCF-7), lung carcinoma (NCI-H292), pro-myelocytic leukemia (HL-60), and cervical adenocarcinoma (HEP-2) human cell lines, and pro-myelocytic leukemia cells lines (HL-60) were found to be the most sensitive to all the essential oils tested than the others. This is the first report on larvicidal and cytotoxic activities of these essential oils.

New flavone and other compounds from Tephrosia egregia: assessing the cytotoxic effect on human tumor cell lines

ABSTRACT The organic extracts from stems, roots and leaves of Tephrosia egregia Sandwith, Fabaceae, provided a new flavone, 5-hydroxy-8-(1",2"-epoxy-3"-hydroxy-3"-methylbutyl)-7-methoxyflavone (1), in addition to eleven known compounds: pongaflavone (2), praecansone B (3), 12a-hydroxyrotenone (4), praecansone A, 2',6'-dimethoxy-4',5'-(2",2"-dimethyl)-pyranochalcone, pongachalcone, maackiain, β-sistosterol and its glucoside, p-cumaric acid and cinnamic acid. The structures of all compounds were established on the basis of spectroscopic methods, mainly 1D and 2D NMR and HRESIMS, involving comparison with literature data. Cytotoxicity of compounds 1-4 was evaluated against AGP-01 (cancerous ascitic fluid), HCT-116 (colon adenocarcinoma), HL-60 (leukemia), PC-3 (prostate carcinoma), SF-295 (glioblastoma) and SKMEL 28 (melanoma) cell lines.

Chemical constituents from Bauhinia acuruana and their cytotoxicity

ABSTRACT Phytochemical investigation of Bauhinia acuruana Moric., Fabaceae, resulted in the isolation of sixteen constituents, including two new compounds 2'-hydroxy-2,3,5-trimethoxybibenzyl (1), (2R,3S)-2-(3,4'-dihydroxyphenyl)-5-methoxy-6-methylchroman-3,7-diol (2), together with fourteen known ones (3-16). The structures of the compounds were established by spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR data, followed by comparison with previously reported data from the literature. Compounds 1, 2, 6, 7, 8 and 9 were evaluated for their cytotoxicity, which turned out to be marginal in a panel of six human cancer cell lines.

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C chemical shift assignments.

A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C chemical shift assignments

ABSTRACT A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.

New Cytotoxic Bibenzyl and Other Constituents from Bauhinia ungulata L. (Fabaceae).

A new bibenzyl, 2'-hydroxy-3,5-dimethoxy-4-methylbibenzyl (1) and four known compounds identified as 2'-hydroxy-3,5-dimethoxybibenzyl (2), liquiritigenin (3), guibourtinidol (4) and fisetinidol (5) were isolated from the roots of Bauhinia ungulata L. Phytochemical investigations of the stems of B. ungulata led to the isolation of the known compounds identified as liquiritigenin (3), guibourtinidol (4), fisetinidol (5), taraxerol (6), betulinic acid (7), taraxerone (8), glutinol (9), a mixture of sitosterol (10) and stigmasterol (11), pacharin (12), naringenin (13) and eriodictyol (14). The structures of these compounds were elucidated on the basis of their spectral data (IR, MS, 1D- and 2D-NMR). The cytotoxicity of the bibenzyl 1 has been evaluated against four human cancer cell lines, showing the IC50 values of 4.3 and 6.5 µg ml-1 against pro-myelocytic leukemia (HL-60) and cervical adenocarcinoma (HEP-2) cell lines, respectively. This article also registers for the first time the 13 C-NMR data of the known bibenzyl 2.

Lithocholic acid and derivatives: Antibacterial activity.

In order to develop bioactive lithocholic acid derivatives, we prepared fifteen semi-synthetic compounds through modification at C-3 and/or C-24. The reactions showed yields ranging from 37% to 100%. The structures of all compounds obtained were identified on the basis of their spectral data (IR, MS, 1D- and 2D-NMR). The activity of lithocholic acid and derivatives was evaluated against the growth of Escherichia coli, Staphylococcus aureus, Bacillus cereus and Pseudomonas aeruginosa. The derivative 3α-formyloxy-5ß-cholan-24-oic acid (LA-06) showed the best activity, with MIC values of 0.0790 mM against E. coli (Ec 27) and B. cereus in both cases, and 0.0395 mM against S. aureus (ATCC 12692). Lithocholic acid and the derivatives with MIC⩽1.2 mM were evaluated on the susceptibility of some bacterial pathogens to the aminoglycoside antibiotics neomycin, amikacin and gentamicin was evaluated. There are no previously reported studies about these compounds as modifiers of the action of antibiotics or any other drugs.

Antibacterial and antioxidant activities of ursolic acid and derivatives.

Ursolic acid, an important bioactive compound, was isolated from ethanol extract of aerial parts of Sambucus australis. In order to develop bioactive ursolic acid derivatives, two semi-synthetic compounds were obtained through modification at C-3. The antibacterial activity of the ursolic acid and its derivatives was investigated. The microdilution method was used for determination of the minimal inhibitory concentration (MIC), against twelve bacterial strains. The influence of ursolic acid and its derivatives on the susceptibility of some bacterial pathogens to the aminoglycosides antibiotics neomycin, amikacin, kanamycin and gentamicin was evaluated. The most representative synergistic effect was observed by 3ß-formyloxy-urs-12-en-28-oic acid at the concentration of 64 µg/mL in combination with kanamycin against Escherichia coli (27), a multidrug-resistant clinical isolate from sputum, with reduction of MIC value from 128 µg/mL to 8 µg/mL. Ursolic acid and its derivatives were examined for their radical scavenger activity using the DPPH assay, and showed significant activity.

Larvicidal activity against Aedes aegypti of essential oils from northeast Brazil.

The larvicidal activities of essential oils from the leaves of Artemisia vulgaris L., Cymbopogon flexuosus (Nees ex Steud.) Wats. and Piper tuberculatum Jacq. were evaluated using third-instar larvae of Aedes aegypti. The essential oils were obtained by hydrodistillation and analyzed by GC and GC-MS. The essential oil of P. tuberculqatum had the lowest LC50 value (106.3 +/- 2.2 microg/mL), followed by that of A. vulgaris (114.1 +/- 1.7 microg/mL) and C. flexuosus (121.6 +/- 0.8 micro/mL). The results show that these essential oils may be potent sources of natural larvicides.

New indole alkaloid from Peschiera affinis (Apocynaceae).

A new indole alkaloid of the pyridocarbazole type, named 6N-hydroxy-olivacine, and two known compounds, 2N-oxide-olivacine and olivacine, were isolated from roots of Peschiera affinis. The structures of the compounds were determined by spectroscopic {IR and extensive NMR (COSY, HMQC, HMBCand NOESY)} and EIMS analysis.

Effect of subinihibitory and inhibitory concentrations of Plectranthus amboinicus (Lour.) Spreng essential oil on Klebsiella pneumoniae.

We evaluated the antimicrobial activity and some mechanisms used by subinhibitory and inhibitory concentrations of the essential oil, obtained from leaves of Plectranthus amboinicus, against a standard strain of Klebsiella pneumoniae and 5 multiresistant clinical isolates of the bacteria. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), the rate of kill and the pH sensitivity of the essential oil were determined by microdilution tests performed in 96-well plates. Subinhibitory and inhibitory concentrations of the essential oil were tested in order to check its action on K. pneumoniae membrane permeability, capsule expression, urease activity and cell morphology. The MIC and MBC of the essential oil were 0.09±0.01%. A complete inhibition of the bacterial growth was observed after 2 h of incubation with twice the MIC of the essential oil. A better MIC was found when neutral or alkaline pH broth was used. Alteration in membrane permeability was found by the increase of crystal violet uptake when the bacteria were incubated with twice the MIC levels of the essential oil. The urease activity could be prevented when all the subinhibitory concentrations were tested in comparison to the untreated group (p<0.001). Alteration of the bacterial morphology besides inhibition of the capsule expression was verified by atomic force microscopy, and Anthony's stain method, respectively. Our data allow us to conclude that the essential oil of P. amboinicus can be a good candidate for future research.

Effects of Myrcia ovata Cambess., essential oil on planktonic growth of gastrointestinal microorganisms and biofilm formation of Enterococcus faecalis

The essential oil from the leaves of Myrcia ovata Cambess., commonly used in Brazil for the treatment of gastric illnesses, was screened for antimicrobial activity and action in the formation of microbial biofilms by Enterococcus faecalis. The oil was obtained by hydrodistillation using a clevenger-type system. Its chemical composition was analyzed using GC and GC-MS. Both MIC and MBC of the essential oil were determined by broth microdilution techniques and agar dilution method. The essential oil showed antimicrobial activity against E. faecalis, Escherichia coli, Pseudomonas aeruginosa, Salmonella choleraesuis, Staphylococcus aureus, Streptococcus pneumoniae and Candida parapsilosis. The results showed that the essential oil of M. ovata Cambess. was effective against the formation of biofilm by E. faecalis when compared with the control. Four volatile compounds, representing 92.1 percent of the oil, were identified and geranial was the major component (50.4 percent). At the best of our knowledge, this is the first report of the chemical composition and antimicrobial activity of the essential oil from leaves of M. ovata.

Effects of myrcia ovata cambess. Essential oil on planktonic growth of gastrointestinal microorganisms and biofilm formation of enterococcus faecalis.

The essential oil from the leaves of Myrcia ovata Cambess., commonly used in Brazil for the treatment of gastric illnesses, was screened for antimicrobial activity and action in the formation of microbial biofilms by Enterococcus faecalis. The oil was obtained by hydrodistillation using a clevenger-type system. Its chemical composition was analyzed using GC and GC-MS. Both MIC and MBC of the essential oil were determined by broth microdilution techniques and agar dilution method. The essential oil showed antimicrobial activity against E. faecalis, Escherichia coli, Pseudomonas aeruginosa, Salmonella choleraesuis, Staphylococcus aureus, Streptococcus pneumoniae and Candida parapsilosis. The results showed that the essential oil of M. ovata Cambess. was effective against the formation of biofilm by E. faecalis when compared with the control. Four volatile compounds, representing 92.1 % of the oil, were identified and geranial was the major component (50.4 %). At the best of our knowledge, this is the first report of the chemical composition and antimicrobial activity of the essential oil from leaves of M. ovata.

Chemical constituents and larvicidal activity of Hymenaea courbaril fruit peel.

The chemical compositions of the essential oils from the peel of ripe and unripe fruits of Hymenaea courbaril L., obtained by hydrodistillation, were analyzed by GC and GC-MS. The main constituents of the essential oil from the peel of the ripe fruits were the sesquiterpenes alpha-copaene (11.1%), spathulenol (10.1%) and beta-selinene (8.2%), while germacrene-D (31.9%), beta-caryophyllene (27.1%) and bicyclogermacrene (6.5%) were the major compounds in the oil from unripe fruits. The essential oils were tested against Aedes aegypti larvae and showed LC50 values of 14.8 +/- 0.4 microg/mL and 28.4 +/- 0.3 microg/mL for the ripe and unripe fruit peel oils, respectively. From the peel of the ripe fruits, the diterpenes zanzibaric acid and isoozic acid were isolated, along with the sesquiterpene caryolane-1,9beta-diol. To the best of our knowledge, this is the first report of this sesquiterpene in the genus. The structures of all compounds isolated were identified on the basis of their spectral data (IR, MS, 1D- and 2D-NMR) and by comparison with literature spectral data.

Antioxidant and larvicidal activities of Tephrosia egregia Sandw against Aedes aegypti.

The antioxidant and larvicidal activities of Tephrosia egregia extracts and its major component, dehydrorotenone, were studied. High antioxidant activity was found for dehydrorotenone and methanol and ethyl acetate extracts from roots and stems, respectively. Among the tested extracts, the hexane extract from stems showed potent larvicidal activity (LC50 12.88 +/- 0.64) while low activity was found for dehydrorotenone.

Estudo fitoquímico e avaliação da atividade larvicida de Pterodon polygalaeflorus Benth (Leguminosae) sobre Aedes aegypti / Phytotochemical study and evaluation of larvicidal activity of Pterodon polygalaeflorus Benth (Leguminosae) against Aedes aegypti

Estudo fitoquímico dos extratos hexânico e metanólico dos frutos de Pterodon polygalaeflorus Benth forneceu três diterpenos furânicos: 6-alfa-acetoxivouacapano, 6-alfa-hidroxivouacapano e vouacapano, sendo este ultimo relatado pela primeira vez como produto natural. Avaliação da atividade sobre larvas de estágio 3 de Aedes aegypti de 6-alfa-acetoxivouacapano, dos extratos hexânico e metanólico dos frutos de P. polygalaeflorus e de seu óleo essencial também é relatada. Apenas o extrato hexânico mostrou boa atividade com CL50 23,99 ± 0,75 µg/mL, podendo ser considerado um potencial agente larvicida.

Chemical investigation of the hexane and methanol extracts of the fruits of Pterodon polygalaeflorus (Leguminosae) resulted in the isolation and identification of furanic diterpenes: 6-alpha-acetoxivouacapane, 6-alpha-hidroxyvouacapane and vouacapane, which is related by the first time as a natural product. The structures of these compounds were established by spectroscopic analysis, including 2D NMR experiments. The 6-alpha-acetoxivouacapane, the hexane and methanol extracts, and the essential oil were evaluated on 3rd instar larvae of Aedes aegypti and only the hexane extract showed good larvicidal activity with LC50 23.99 ± 0.75 µg/mL.

Insecticidal activity and chemical composition of volatile oils from Hyptis martiusii Benth.

The essential oils from leaves and inflorescences of Hyptis martiusii Benth were analyzed by GC-MS. Twenty-six compounds representing 93.2% of the essential oil of leaves were characterized; Delta-3-carene (22.5%), 1,8-cineole (24.27%), beta-caryophyllene (6.15%), and bicyclogermacrene (6.32%) were found as the major components. In the essential oil of inflorescences 27 compounds representing 87.7% of the oil were identified. The major components were Delta-3-carene (13.5%), alpha-pinene (5.78%), beta-caryophyllene (6.59%), viridiflorene (8.25%), and germacrene B (5.21%). The essential oil of leaves and 1,8-cineole showed pronounced insecticidal effect against Aedes aegypti larvae and Bemisia argentifolii, the vectors of dengue fever and white fly fruit plague, respectively.

New enamine derivatives of lapachol and biological activity.

A convenient synthesis of the new enamine derivatives 2-(4-morpholinyl)-3-(3-methyl-2-butenyl)-1,4-naphthalenedione, 2-(1-piperidinyl)-3-(3-methyl-2-butenyl)-1,4-naphtalenedione and 2-(1-pyrrolidinyl)-3-(3-methyl-2-butenyl)-1,4-naphthalenedione was carried out from natural 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthalenedione (lapachol) and morpholine, piperidine and pyrrolidine. The structures of the products were established mainly by NMR analysis, including 2D experiments. Biological activities of these products were evaluated against Artemia salina, Aedes aegypti and cytotoxicity using A549 human breast cells.