Resolvin E1's Antimicrobial Potential Against Aggregatibacter Actinomycetemcomitans.

Background: Microorganisms along with host response play a key role in the development of periodontal and peri-implant infections. Advanced periodontal and peri-implant diseases are most likely associated with bacterial plaques that trigger host immune response and eventually lead to the destruction of the attachment apparatus and bone loss around a tooth or a dental implant. A recent systematic review and meta-analysis revealed that Aggregatibacter actinomycetemcomitans had the highest association with peri-implantitis. Resolvin E1 (RvE1) is part of the specialized pro-resolving lipid mediator family biosynthesized from omega-3, polyunsaturated fatty acids (PUFAs), and eicosapentaenoic acid (EPA). Although RvE1 is an established anti-inflammatory agent, it was found that its application as a treatment or as a preventive drug had an indirect effect on the subgingival microbiota of both rats and rabbits with experimental periodontitis. Aim: The aim of this study is to evaluate the direct antimicrobial effect of RvE1 on Aggregatibacter actinomycetemcomitans bacteria. Materials and Methods: The study comprised three groups that underwent minimum inhibitory concentration (MIC) against Aggregatibacter actinomycetemcomitans. The first group was tested with the RvE1 working concentration of 5 ug/ml, the second group was tested with ethanol (EtOH), 10% as the working concentration, and the final group was diluted in phosphate-buffered saline (PBS) as the positive control. Optical density (OD600) was used for the comparison of bacterial growth among the tested groups. The experiment was conducted in three biological replicates. Data were analyzed using SPSS, and results were analyzed by using one-way analysis of variance (ANOVA) followed by post-hoc Bonferroni using a minimum level of significance (P-value) of 0.05. Results: Minimum inhibitory concentration was 1.25 µg/ml and 5% for RvE1 and EtOH, respectively. RvE1's mean optical density (OD600) was 0.156 ± 0.021 and was significantly lower compared with all the other groups (P-value < 0.01). The EtOH group (mean OD600 0.178 ± 0.013) and the PBS group (mean OD600 0.1855 ± 0.022) did not reveal a significant difference (P-value = 0.185). Conclusion: RvE1 demonstrated significant antimicrobial activity against A. actinomycetemcomitans with an MIC of 1.25 µg/ml. The RvE1 group showed significantly lower bacterial growth compared to the EtOH and PBS groups.

New Conjugated Compound T5 Epidioxy-Sterol-ANB Inhibits the Growth of Mycobacterium tuberculosis Affecting the Cholesterol and Folate Pathways.

The upsurge and persistence of drug resistant strains of Mycobacterium tuberculosis (Mtb) is an important limitant to the battery of drugs available for the elimination of tuberculosis (TB). To avoid future scarcity of antibiotics against Mtb, it is important to discover new effective anti-mycobacterial agents. In this study, we present data from a series of experiments to determine in vitro and in vivo anti-mycobacterial activity of a library of epidioxy-sterol analogs. We test 15 compounds for their ability to reduce the viability of Mtb. We found that one compound called T5 epidioxy-sterol-ANB display significant potency against Mtb in vitro specifically inside macrophages but without effectivity in axenic cultures. A viability assay confirms that this T5 compound is less toxic for macrophages in vitro as compared to the current Mtb drug Rifampicin at higher concentrations. We use a transcriptomic analysis of Mtb inside macrophages after T5 epidioxy-sterol-ANB treatment, and we found a significant down-regulation of enzymes involved in the cholesterol and folic acid pathways. In vivo, significant differences were found in the lungs and spleen CFUs of Mtb infected mice treated with the T5 epidioxy-sterol-ANB as compared with the untreated control group, which provides additional evidence of the effectivity of the T5 compound. Altogether these results confirm the potential of this T5 epidioxy-sterol-ANB compound against Mtb.

Ruthenium Chloride-Induced Oxidative Cyclization of Trans-Resveratrol to (±)-ε-Viniferin and Antimicrobial and Antibiofilm Activity Against Streptococcus pneumoniae.

Polyphenol ε-viniferin (2) is a protective phytochemical found in several plant families. Here, we report a simple and effective method for the synthesis of (±)-ε-viniferin (2) as major product and (±)-(E)-ω-viniferin (3) as a minor product. Synthesized viniferin compounds and standard viniferin were analyzed for antibacterial and antibiofilm activity against Gram-positive bacteria Streptococcus pneumoniae. The minimum inhibitory concentrations (MICs) of (±)-ε-viniferin (2) and standard viniferin were 20 µm. However, the MICs of (±)-(E)-ω-viniferin (3) and compound 8 were 40 µm. Although viniferin significantly (p < 0.05) reduced pre-established in vitro biofilms and killed bacteria within the biofilm, it was unable to prevent biofilm formation at sub-MIC concentrations. The time kill experiment revealed that viniferin killed bacteria and reduced 2.8 log10 bacteria at 2 × MIC concentration after 24 h. Scanning electron microscope (SEM) analysis and live/dead biofilm staining of pre-established biofilms revealed that viniferin treatment disrupts membrane integrity of biofilm bacteria. Crystal violet absorption, total protein, and DNA and RNA release revealed that viniferin alters bacterial cell permeability, eventually killing bacteria.

Synthesis, and structure-activity relationship for C(4) and/or C(5) thienyl substituted pyrimidines, as a new family of antimycobacterial compounds.

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis of C(4) and/or C(5) mono(thienyl) and di(thienyl) substituted pyrimidines from commercially available 5-bromopyrimidine. All new pyrimidines were found to be active in micromolar concentrations in vitro against H37Rv, avium, terrae, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The data for acute in vivo toxicity in mice have been obtained for these compounds which appear to be promising antitubercular agents.

Furan type lignans with antimycobacterial activity / Lignanos del tipo furano con actividad antimicobacterial

Compounds such as triclosan, diclofenac and trimetropin posses antibacterial activity, including mycobacterial; their structures are based on two aromatic rings joined by a methylene or a heteroatom. Since a similar structural system is found in natural diarylfuran- based lignans, we studied plants known with this type of lignans, as potential active against Mycobacterium tuberculosis. Fractions of the active extracts were tested for anti-TB activity and their chemical constituents analyzed by NMR spectroscopy. Several extracts and chromatographical fractions exhibited > 90 percent inhibition of M. tuberculosis at 128 ug/mL. Methylpluviatilol, a pure compound isolated from Virola sebifera, was active at this concentration.. These findings suggest that plant species of the families here studied may yield novel lead compounds for the development of antimycobacterial agents.

Compuestos tales como triclosan, diclofenac y trimetoprim poseen actividad antibacterial, incluyendo la antimicobacterial; sus estructuras están basadas en dos anillos aromáticos unidos por un metileno o un heteroátomo. Debido a que en la naturaleza se encuentra un sistema estructural similar del tipo diarilfurano en los lignanos, así como otros subtipos, nosotros estudiamos plantas contra Mycobacterium tuberculosis, de las que se sabe contienen lignanos Las fracciones cromatográficas de los extractos activos fueron ensayadas para actividad anti.Tb y sus constituyentes químicos se analizaron por espectroscopía de RMN. Varios extractos y fracciones cromatográficas exhibieron una inhibición superior al 90 por ciento a 128 ug/mL; el compuesto metilpluviatilol, aislado de mostró una inhibición del 99 por ciento a esa concentración. Esos hechos sugieren que las especies de plantas de las familias aquí estudiadas podrían suministrar nuevos compuestos líderes para el desarrollo de agentes antimicobacteriales.

Synthesis and antituberculosis activity of novel 5-styryl-4-(hetero)aryl-pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and S(N)(H) reactions.

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis of 5-styryl-4-(hetero)aryl substituted pyrimidines from commercially available 5-bromopyrimidine. All intermediate 5-bromo-4-(hetero)aryl substituted pyrimidines and also the targeted 5-styryl-4-(hetero)arylpyrimidines were found to be active in micromolar concentrations in vitro against Mycobacterium tuberculosis H37Rv, avium, terrae, and multi-drug-resistant strain isolated from tuberculosis patients in Ural region (Russia). It has been found that some of these compounds possess a low toxicity and have a bacteriostatic effect, comparable and even higher with that of first-line antituberculosis drugs.

Isoniazid-gelatin conjugate microparticles containing rifampicin for the treatment of tuberculosis.

OBJECTIVES: In this work, a new polymeric microparticle system based on gelatin covalently bound to isoniazid (ISN) and containing rifampicin (RFP) was prepared by spray-drying technique. Microparticle aptitude to nebulisation and their capability of interacting with A549, alveolar basal epithelial cells, were evaluated in vitro. METHODS: Microparticles were obtained by spray drying, and their morphology, size, zeta potential, thermotropic behaviour and nebulisation ability were evaluated. KEY FINDINGS: Microparticles were positively charged with a mean size of 4.88 ± 0.3 µm. Microspheres were able to incorporate both RFP and ISN: encapsulation efficiency was 51 ± 6% and 22 ± 1%, respectively. X-ray diffraction study showed a new extensive and flattened diffraction peak providing evidence that the drugs were dispersed into the microparticles. Differential scanning calorimetry analysis confirmed effective interactions between gelatin and drug molecules by the presence of new transition peaks. Fifty-nine per cent of used microparticles were aerosolised. In-vitro toxicity studies on A549 alveolar basal epithelial cells showed that microparticles decreased cytotoxicity in comparison with the RFP solution. Laser scanning confocal microscopy observation confirmed that fluorescent probes delivered by microparticles are efficiently internalised in A549 cells. CONCLUSIONS: Overall, microparticles based on gelatin covalently bound to ISN and containing RFP showed a promising behaviour for pulmonary drug delivery.