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.

HPLC/DAD, Antibacterial and Antioxidant Activities of Plectranthus Species (Lamiaceae) Combined with the Chemometric Calculations.

The increase in antibiotic resistance and the emergence of new bacterial infections have intensified the research for natural products from plants with associated therapy. This study aimed to verify the antibacterial and antioxidant activity of crude extracts of the genus Plectranthus species, being the first report on the modulation of aminoglycosides antibiotic activity by Plectranthus amboinicus extracts. The chemical composition was obtained by chemical prospecting and High-Performance Liquid Chromatography with diode arrangement detector (HPLC/DAD). The antibacterial activities of the extracts alone or in association with aminoglycosides were analyzed using the microdilution test. The antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The phytochemical prospection allowed the flavonoids, saponins, tannins and triterpenoids to be identified. Quercetin, rutin, gallic acid, chlorogenic acid, caffeic acid, catechin, kaempferol, glycosylated kaempferol, quercitrin, and isoquercitrin were identified and quantified. The principal component analysis (PCA) observed the influence of flavonoids and phenolic acids from Plectranthus species on studied activities. Phytochemical tests with the extracts indicated, especially, the presence of flavonoids, confirmed by quantitative analysis by HPLC. The results revealed antibacterial activities, and synergistic effects combined with aminoglycosides, as well as antioxidant potential, especially for P. ornatus species, with IC50 of 32.21 µg/mL. Multivariate analyzes show that the inclusion of data from the antioxidant and antibacterial activity suggests that the antioxidant effect of these species presents a significant contribution to the synergistic effect of phytoconstituents, especially based on the flavonoid contents. The results of this study suggest the antibacterial activity of Plectranthus extracts, as well as their potential in modifying the resistance of the analyzed aminoglycosides.

Effect of Vitamin K3 Inhibiting the Function of NorA Efflux Pump and Its Gene Expression on Staphylococcus aureus.

Resistance to antibiotics has made diseases that previously healed easily become more difficult to treat. Staphylococcus aureus is an important cause of hospital-acquired infections and multi-drug resistant. NorA efflux pump, present in bacteria S. aureus, is synthesized by the expression of the norA gene. Menadione, also known as vitamin K3, is one of the synthetic forms of vitamin K. Therefore, the aim of this study is to verify the menadione effect on efflux inhibition through NorA pump gene expression inhibition and assess the effects of menadione in bacterial membrane. The effect of menadione as an efflux pump inhibitor (EPI) was evaluated by the microdilution method, fluorimetry, electron microscopy, and by RT-qPCR to evaluate gene expression. In the molecular docking, association with menadione induces increased fluorescence intensity. Menadione was observed (100% of the clusters) interacting with residues ILE12, ILE15, PHE16, ILE19, PHE47, GLN51, ALA105, and MET109 from NorA. The results showed the norA gene had its expression significantly diminished in the presence of menadione. The simulation showed that several menadione molecules were able to go through the bilayer and allow the entry of water molecules into the hydrophobic regions of the bilayer. When present within membranes, menadione may have caused membrane structural changes resulting in a decline of the signaling pathways involved in norA expression. Menadione demonstrated to be an efflux pump inhibitor with dual mechanism: affecting the efflux pump by direct interaction with protein NorA and indirectly inhibiting the norA gene expression, possibly by affecting regulators present in the membrane altered by menadione.

Synthesis of Silver Nanoparticles Using Odontosoria chinensis (L.) J. Sm. and Evaluation of their Biological Potentials.

The present study was aimed to synthesize silver nanoparticles (AgNPs) from the aqueous extracts of Odontosoria chinensis (L.) J. Sm. and the synthesized AgNPs were examined for their biopotentials. The Odontosoria chinensis extracts were added to 1 mM AgNO3 solution with different ratios viz., 0.5: 9.5, 1:9, 1.5: 8.5 and 2: 8 ratios for the reduction of Ag ions. After reduction, the AgNPs of Odontosoria chinensis were analyzed spectroscopically for further confirmation. The synthesized AgNPs of Odontosoria chinensis were characterized by pH, ultra violet-visible spectroscopy (UV-Vis), Fourier transform-infra red spectroscopy (FT-IR), scanning electron microscopy-energy dispersive X-ray analysis (SEM-EDAX) and X-Ray diffraction (XRD). The time taken for the complete reduction of Silver (Ag) in solution to nanoparticle was 10 min. The O. chinensis aqueous extracts mediated silver nanoparticles showed a broad peak with distinct absorption at around 400-420 nm and confirmed the silver nanoparticle formation. FT-IR results also confirmed the existence of organic materials in the silver nanoparticles of O. chinensis. The EDX spectra of AgNPs of O. chinenesis revealed the occurrence of a strong Ag peak. The synthesis of AgNPs of O. chinenesis was confirmed with the existence of a peak at 46.228°. The toxic potential of AgNPs of O. chinenesis showed varied percentage mortality with the LC50 values of 134.68 µL/ 50 mL and 76.5 µL/50 mL, respectively. The anti-inflammatory and anti-diabetic activities of aqueous and AgNPs of O. chinenesis were statistically significant at p < 0.05 level. Conclusion: The results demonstrated the toxicity, anti-diabetic and anti-inflammatory potential of the studied AgNPs. The synthesized nanoparticles of Odontosoria chinensis could be tested as an alternative to anticancer, anti-diabetic and anti-inflammatory drugs.

Annona Genus: Traditional Uses, Phytochemistry and Biological Activities.

Species from the Annona (Anonaceae) genus are used in traditional medicine for the treatment of various diseases. Ethnobotanical studies provide information regarding the plant part and the preparation method being used, while scientific studies such as in vitro, in vivo, and clinical tests can provide evidence supporting ethnopharmacological reports, directing studies towards the isolation of compounds which may be active for specific pathologies. Annona muricata and Annona squamosa were the most commonly reported species from those studied, with Annona cherimola and Annona classiflora also standing out. Acetogenins were the most commonly isolated metabolite class due to their cytotoxic properties, with flavonoids, alkaloids, steroids, and peptides also being reported. Many species from the Annona genus have proven biological activities, such as antitumor, antioxidant, antimicrobial and antifungal. The present review had as its objective to facilitate access to ethnobotanical, chemical and biological information in order to direct future researches.

Characterization, antibacterial activity and antibiotic modifying action of the Caryocar coriaceum Wittm. pulp and almond fixed oil.

In this study the physicochemical characterization of the pulp and almond fixed oil was carried out; their antibacterial activity and aminoglycoside antibiotic modifying action against standard and multiresistant Gram-positive and -negative bacteria were investigated using the broth microdilution assay. Physical properties such as moisture, pH, acidity, peroxide index, relative density and refractive index indicate stability and chemical quality of the oils. In the GC/MS chemical composition analysis, a high unsaturated fatty acid content and the presence of oleic and palmitic acids were observed in the oils. In the antibacterial assay, more significant results were obtained for Escherichia coli, while other standard and multi-resistant strains presented MIC values ≥ 1024 µg/mL. Furthermore, the fixed oils in association with antibiotics were able to significantly improve antibacterial activity against S. aureus with a reduction in MICs.

Antibiotic-Potentiating Activity of Phanostenine Isolated from Cissampelos sympodialis Eichler.

Cissampelos sympodialis Eichler is well studied and investigated for its antiasthmatic properties, but there are no data in the literature describing antibacterial properties of alkaloids isolated from this botanical species. This work reports the isolation and characterization of phanostenine obtained from roots of C. sympodialis and describes for the first time its antimicrobial and antibiotic modulatory properties. Phanostenine was first isolated from Cissampelos sympodialis and its antibacterial activities were determined. Chemical structures of the alkaloid isolate were determined using spectroscopic and chemical analyses. Phanostenine was also tested for its antibacterial activity against standard strains and clinical isolates of Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentration (MIC) was determined in a microdilution assay and for the evaluation of antibiotic resistance-modifying activity. MIC of the antibiotics was determined in the presence or absence of phanostenine at sub-inhibitory concentrations. The evaluation of antibacterial activity by microdilution assay showed activity for all strains with better values against S. aureus ATCC 12692 and E. coli 27 (787.69 mm). The evaluation of aminoglycoside antibiotic resistance-modifying activity showed reduction in the MIC of the aminoglycosides (amikacin, gentamicin and neomycin) when associated with phanostenine, MIC reduction of antibiotics ranging from 21 % to 80 %. The data demonstrated that phanostenine possesses a relevant ability to modify the antibiotic activity in vitro. We can suggest that phanostenine presents itself as a promising tool as an adjuvant for novel antibiotics formulations against bacterial resistance.

LC-MS analysis and cytoprotective effect against the mercurium and aluminium toxicity by bioactive products of Psidium brownianum Mart. ex DC.

This study aimed to verify the chelating, antioxidant and cytoprotective activities of Psidium brownianum Mart. Ex DC against mercury and aluminum. The ethanolic extract, as well as the tannic and flavonoid fractions, were prepared and subjected to liquid chromatography-mass spectrometry analysis. Ferric ion reduction and antioxidant activity measurement using the FRAP method were performed with P. brownianum. After determining the sub-allelopathic doses, germination tests using Lactuca sativa (lettuce) seeds were performed. The main compounds identified in the extract and fractions were: quercetin and its derivatives; myricetin and its derivatives; gallic acid; ellagic acid; quinic acid and gallocatechin. The Minimum Inhibitory Concentration (MIC) for all samples were ≥ 1024 µg/mL. The flavonoid fraction in association with mercury chloride demonstrated cytoprotection (p < 0.001). The sub-allelopathic concentration used was 64 µg/mL. The extract and fractions were cytoprotective for radicles and caulicles when assayed in association with mercury and against aluminum for radicles. This suggests that the P. brownianum extract and its fractions present cytoprotective activity, possibly related to the antioxidant effect of secondary metabolites, especially flavonoids.

Psidium guajava bioactive product chemical analysis and heavy metal toxicity reduction.

The present study had as its objective to verify the Psidium guajava var. Pomifera L. chelating, antioxidant and cytoprotective effects against mercury and aluminum. The ethanolic extract, tannic and flavonoid fractions were subjected to LC-MS analysis. The Ferric Reducing Antioxidant Power (FRAP) and ferric ion reduction demonstrated a present antioxidant activity. The fungicidal and bactericidal activity of these metals were established. After determining the sub-allelopathic doses, germination tests using Lactuca sativa were performed. Quercetin and its derivatives were the main compounds identified in the extract and the fractions. Mercury chloride significantly reduced the bactericidal effect of the flavonoid fraction (p < 0.001). None of the fractions were cytoprotective against mercury or aluminum in the fungal model assays. Using a sub-allelopathic concentration (64 µg/mL), the ethanolic extract, flavonoid and tannic fractions were found to be cytoprotective against aluminum for radicles, however only the tannic fraction was cytoprotective for caulicles. These data suggest that natural P. guajava products are promising cytoprotective compound sources. This activity may be related to the antioxidant effect of secondary metabolites, mainly flavonoids. Our results point to a potential for environmental intervention product and technique development aimed at mitigating contamination by toxic metals such as mercury and aluminum.

Phytotoxicity reduction of the mercury chloride effect by natural products from Eugenia jambolana Lam.: A new strategy against the toxic metal pollution.

The objective of this work was to evaluate the antioxidant, metal chelating and cytoprotective activity of the Eugenia jambolana Lam. extract, as well as of its flavonoid and tannic fractions, against the action of Mercury Chloride (HgCl2). Flavonoids were quantified and an LC-MS chromatographic analysis was performed to identify secondary metabolites. Fe2+ and Fe3+ chelation tests and antioxidant activity were carried out using the FRAP method. Microbiological tests were performed by microdilution to determine the Minimum Inhibitory Concentration (MIC). From these results the Minimum Bactericidal (MBC) and Minimum Fungicide Concentration (MFC) were evaluated. The allelopathy and cytoprotection assays were performed using eukaryotic and prokaryotic models. The results revealed the presence of phenolic acids and flavonoids in the E. jambolana extract and fractions. The sub-allelopathic concentration (64 µg/mL) was used and the results demonstrated the E. jambolana potential cytoprotective effect against mercury chloride.

Antioxidative effect and phytochemical profile of natural products from the fruits of "babaçu" (Orbignia speciose) and "buriti" (Mauritia flexuosa).

Orbignya speciosa and Mauritia flexuosa are two native palm tree species found in Brazil. Their fruits are rich in edible fixed oils, which are used for many purposes in industry, such as in the manufacture of soaps, surfactants and margarines. The aim of this work was to characterize the chemical profiles and antioxidant properties of the methanol extracts obtained from the fruits of O. speciosa and M. flexuosa. The chemical prospection was carried out using specific qualitative tests to evaluate the presence of phenolic compounds (tannins and flavonoids) in the extracts of both species. The antioxidant properties of the extracts were analyzed by the following methods: production of thiobarbituric acid reactive substances (TBARS) from phospholipids, deoxyribose degradation, radical-scavenging activity-DPPH, iron chelation assay and ferric-reducing antioxidant power (FRAP). The methanolic extracts obtained from M. flexuosa and O. speciosa presented significant antioxidant activities, although M. flexuosa presented higher antioxidant activity than O. speciosa. In conclusion, M. flexuosa and O. speciosa are important sources of antioxidant substances that may be useful in the development of new products to prevent diseases associated with oxidative stress.

Gas Chromatography-Triple Quadrupole Mass Spectrometry Analysis and Vasorelaxant Effect of Essential Oil from Protium heptaphyllum (Aubl.) March.

The Protium heptaphyllum species, also known as Almécega, produces an oily resin, used in folk medicine as an analgesic and anti-inflammatory agent, in healing, and as an expectorant, which is rich in pentacyclic triterpenes and essential oils. In this study, the essential oil obtained by hydrodistillation of Almécega's resin was analyzed by gas chromatography-triple quadrupole mass spectrometry and evaluated for chemical composition and vasorelaxant activity in rat superior mesenteric artery. The main constituents determined by gas chromatography-triple quadrupole mass spectrometry were limonene, p-cineole, and o-cymene. In intact rings precontracted with phenylephrine (Phe 1 µM), EOPh (3-750 µg/mL) induced relaxation, and the essential oil had a concentration-dependent vasorelaxant effect, without involvement of endothelial mediators.

Phenolic composition and medicinal usage of Psidium guajava Linn.: Antifungal activity or inhibition of virulence?

Psidium guajava is a Myrtaceae plant whose medicinal properties are recognized in several locations. The use of teas and tinctures prepared from their leaves has been used to combat infections caused by fungi of the genus Candida. In this study, aqueous extracts of leaves and hydroethanolic were tested to verify the antifungal potential and its chemical composition has been investigated. The microbiological assays were performed by broth microdilution to determine the minimum inhibitory concentration (MIC) and from these the minimum fungicidal concentration was performed (MFC) by subculturing on solid media. A cell viability curve was obtained for demonstration of inhibition of fungal growth of strains of Candida albicans and Candida tropicalis. Tests to check morphological changes by the action of the extracts were performed in microcultive cameras depleted environment at concentrations of MIC/2, MIC and MIC × 2. Extracts analyzed by high performance liquid chromatography demonstrated flavonoids and phenolic acids. The extracts showed fungistatic effect and no fungicide with MIC >8192 µg/mL, MFC above 8192 µg/mL. The IC50 was calculated ranging from 1803.02 to 5623.41 µg/mL. It has been found that the extracts affect the morphological transition capability, preventing the formation of pseudohyphae and hyphae. Teas and tinctures, therefore, have the potential antifungal, by direct contact, causing inhibition of fungal multiplication and its virulence factor, the cell dimorphism, preventing tissue invasion. Further studies are needed to elucidate the biochemical pathways and genes assets involved in these processes.

Evaluation of chemical composition and antiedematogenic activity of the essential oil of Hyptis martiusii Benth.

Evaluations of the therapeutic potential of medicinal plants and their components have been the subject of many studies. Furthermore, the biological activities of various plant species have been reported in various pieces of literature. Hyptis martiusii Benth (Lamiaceae), popularly known as "mad balm" is commonly found in the North, Southeast, and Northeast of Brazil. Its leaves are used ethnobiologically as antiulcerogenic, antimicrobial, antitumor and as insecticide. This study aimed to analyze the chemical composition of the essential oil of H. martiusii Benth (OEHM) by GC/MS as well as its possible topical activity as an antiedematogenic. This is verified by the models of ear edema induced by single (acute edema) and multiple (chronic edema) applications of croton oil topically, and systemically verified through the model of paw edema induced by carrageenan 1%. Doses of 50, 75 and 100 mg/kg OEHM were used in all tests. Chemical analysis of the oil revealed the 1,8-cineole (34.58%) and δ-carene (21:58%) as major components present in the essential oil. On the model of ear edema, acute and chronic OEHM in all the tested doses showed no significant antiedematogenic activity (p < 0.05). The systemic model of paw edema induced by carrageenin showed that a dose of 100 mg/kg effectively reduced swelling by 55.37% in the second hour evaluation when compared to the saline group. The anti-inflammatory systemic effect can give greater bioavailability of the components present in the essential oil and your interference in cytokines and leukotriene, thromboxane and prostaglandin biosynthesis. It is therefore concluded that OEHM presents systemic antiedematogenic activity but not topical activity at these doses.

Psidium guajava L. and Psidium brownianum Mart ex DC.: Chemical composition and anti - Candida effect in association with fluconazole.

The therapeutic combinations have been increasingly used against fungal resistance. Natural products have been evaluated in combination with pharmaceutical drugs in the search for new components able to work together in order to neutralize the multiple resistance mechanisms found in yeasts from the genus Candida. The aqueous and hydroethanolic extracts from Psidium brownianum Mart ex DC. and Psidium guajava L. species were evaluated for their potential to change the effect of commercial pharmaceutical drugs against Candida albicans and Candida tropicalis strains. The tests were performed according to the broth microdilution method. Plate readings were carried out by spectrophotometry, and the data generated the cell viability curve and IC50 of the extracts against the yeasts. A chemical analysis of all the extracts was performed for detection and characterization of the secondary metabolites. The total phenols were quantified in gallic acid eq/g of extract (GAE/g) and the phenolic composition of the extracts was determined by HPLC. Fluconazole and all extracts presented high Minimum Inhibitories Concentrations (MICs). However, when associated with the extracts at sub-inhibitory concentrations (MIC/16), fluconazole had its effect potentiated. A synergistic effect was observed in the combination of fluconazole with Psidium brownianum extracts against all Candida strains. However, for Psidium guajava extracts the synergistic effect was produced mainly against the Candida albicans LM77 and Candida tropicalis INCQS 400042 strains. The IC50 values of fluconazole ranged from 19.22 to 68.1 µg/mL when it was used alone, but from 2.2 to 45.4 µg/mL in the presence of the extracts. The qualitative chemical characterization demonstrated the presence of phenols, flavonoids and tannins among the secondary metabolites. The concentration of total phenols ranged from 49.25 to 80.77 GAE/g in the P. brownianum extracts and from 68.06 to 82.18 GAE/g in the P. guajava extracts. Our results indicated that both P. brownianum and P. guajava extracts are effective on potentiating the effect of fluconazole, and therefore, these plants have the potential for development of new effective drugs for treating fungal infections.

Potentiation of antibiotic activity of aminoglycosides by natural products from Cordia verbenacea DC.

Medicinal plants are often the only therapeutic resource for many communities and ethnic groups. Cordia verbenacea DC., "Erva-baleeira," is one of the species of plants currently used to produce a phytotherapeutic product extracted from its leaves. The present study aimed to establish its chemical profile, antibacterial activity and resistance-modulating potential. The C. verbenacea extracts were prepared from fresh leaves using solvents as methanol and hexane. Ethyl Acetate was used for the preparation of the fraction. Phytochemical screening was carried out using HPLC-DAD for determination and quantification of the secondary metabolites present in the fractions. Antibacterial and resistance-modulation assays were performed to determine minimum inhibitory concentration (MIC) using a microdilution assay. The data were subjected to statistical analysis with two-way ANOVA and Bonferroni posttests. Results of phytochemical prospecting and HPLC analysis of the fractions were in agreement with the literature. The natural products presented moderate antibacterial activity when considering the clinical relevance of a MIC of 256 µg/mL against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, and 512 µg/mL against P. aeruginosa. However, when the fractions were combined with antibiotics we observed a synergic effect, as natural products enhanced the antibacterial effect of aminoglycosides, significantly decreasing the MIC of antibiotics at 12.5%-98.4%. We believe that the data obtained from phytochemical analysis and from antibacterial and resistance modulation assays of C. verbenacea extracts new can open perspectives in the search for new alternatives for the treatment of bacterial infections and stimulate the renewed use of antibiotics with reduced effectiveness due to resistance.

Synthesis, antibacterial and cytotoxic activities of new biflorin-based hydrazones and oximes.

Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution method for determining the minimum inhibitory concentration (MIC) against six bacterial strains. Tests have shown that these derivatives have potential against all bacterial strains. The cytotoxic activity was also evaluated against three strains of cancer cells, but none of the derivatives showed activity.

Additive effect of Lygodium venustum SW. in association with gentamicin.

The aim of this work was to evaluate the interactions between gentamicin and the ethanol extract of the fern Lygodium venustum SW (EELV). The ethanol extract of L. venustum was obtained, the phytocompounds were identified and the EELV was assayed by the checkerboard method with gentamicin against two bacterial strains multiresistant to antibiotics. The antibiotic activity of gentamicin, when associated with the extract, was enhanced in an additive manner against both strains. The results indicated that L. venustum can be a source of secondary metabolites to be used in association with antibiotics as aminoglycosides in the antibiotic chemotherapy against resistant bacteria.

Phytocompounds and modulatory effects of Anacardium microcarpum (cajui) on antibiotic drugs used in clinical infections.

BACKGROUND: The challenge of antibiotic resistance and the emergence of new infections have generated considerable interest in the exploration of natural products from plant origins as combination therapy. In this context, crude ethanolic extract (CEE), ethyl acetate fraction (EAF), and methanolic fraction (MF) from Anacardium microcarpum were tested alone or in combination with antibiotics (amikacin, gentamicin, ciprofloxacin, and imipenem) against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. METHODS: Antibiotic resistance-modifying activity was performed using the microdilution method by determining the minimal inhibitory concentration (MIC). In addition, phytochemical prospecting analyses of tested samples were carried out. RESULTS: Our results indicated that all the extracts showed low antibacterial activity against multidrug-resistant strains (MIC =512 µg/mL). However, addition of CEE, EAF, and MF to the growth medium at the subinhibitory concentration (MIC/8=64 µg/mL) significantly modulated amikacin- and gentamicin-resistant E. coli 06. CEE and EAF also demonstrated a significant (P<0.001) synergism with imipenem against S. aureus. In contrast, MF antagonized the antibacterial effect of ciprofloxacin and gentamicin against P. aeruginosa 03 and S. aureus 10, respectively. Qualitative phytochemical analysis of the extracts revealed the presence of secondary metabolites including phenols, flavonoids, xanthones, chalcones, and tannin pyrogallates. CONCLUSION: Taken together, our results suggest that A. microcarpum is a natural resource with resistance-modifying antibacterial activity that needs to be further investigated to overcome the present resistant-infection problem.

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.