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.

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.

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.

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.

Evaluation of the antifungal activity and modulation between Cajanus cajan (L.) Millsp. leaves and roots ethanolic extracts and conventional antifungals.

BACKGROUND: The use and investigation of natural products with antimicrobial activity from vegeral source have been reported by several researchers. Cajanus cajan (Fabaceae) is a multiple use specie mainly as human food. In popular medicine, diverse parts of the plant are used as sedative and to treat cough, hepatitis, and diabetes. MATERIALS AND METHODS: This study shows the characterization of secondary metabolites present in ehtanolic extracts from leaves and roots of Cajanus cajan by phytochemical prospection. The evaluation of the antifungal activity was performed by the microdilution method, and from the subinhibitory concentrations (MIC 1/8) the modulatory activity of antifungical (fluconazole and ketoconazole) was analyzed by the direct contact assay against C. albicans ATCC40006, Candida krusei ATCC 6538 and Candida tropicalis ATCC 40042. RESULTS: The results showed the presence of tannins, flavonoids, and alkaloids in both extracts as the clinically relevant antifungal activity. The modulatory potential is presented by the antifungal tested against yeasts. CONCLUSION: The extracts studied here have demonstrated to be a new therapeutic source to treat these microorganism-associated diseases.