Selective in vitro Synergistic Evaluation of Probiotic Tolerant morpholinyl- and 4-ethylpiperazinyl-Imidazole-chalcone Derivatives on Gastrointestinal System Pathogens.

Imidazole-chalcone compounds are recognised for their broad-spectrum antimicrobial properties. Probiotic-friendly, selective new-generation antimicrobials prove to be more efficient in combating gastrointestinal system pathogens. The aim of this study is to identify imidazole-chalcone derivatives that probiotics tolerate and evaluate their in vitro synergistic antimicrobial effects on pathogens. In this study, fifteen previously identified imidazole-chalcone derivatives were analyzed for their in vitro antimicrobial properties against gastrointestinal microorganisms. Initially, the antimicrobial activity of pathogens was measured using the agar well diffusion method, while the susceptibility of probiotics was determined by microdilution. The chosen imidazole-chalcone derivatives were assessed for synergistic effects using the checkerboard method. Four imidazole-chalcone derivatives to which probiotic bacteria were tolerant exhibited antibacterial and antifungal activity against the human pathogens tested. To our knowledge, this study is the first to reveal the fractional inhibitory concentration (FIC) of combinations of imidazole-chalcone derivatives. Indeed, the minimum inhibitory concentrations (MIC) for morpholinyl- (ZDO-3f) and 4-ethylpiperazinyl- (ZDO-3 m) imidazole-chalcones were notably low when tested against E. coli and B. subtilis, with values of 31.25 µg/mL and 125 µg/mL, respectively. The combination of morpholinyl- and 4-ethylpiperazinyl derivatives demonstrated an indifferent effect against E. coli, but an additive effect was observed for B. subtilis. Additionally, it was observed that imidazole-chalcone derivatives did not exhibit any inhibitory effects on probiotic organisms like Lactobacillus fermentum (CECT-5716), Lactobacillus rhamnosus (GG), and Lactobacillus casei (RSSK-591). This study demonstrates that imidazole-chalcone derivatives that are well tolerated by probiotics can potentially exert a synergistic effect against gastrointestinal system pathogens.

Antimicrobial evaluation of Tripleurospermum callosum (Boiss. & Heldr.) E. Hossain extracts using in vitro and in vivo Caenorhabditis elegans model against urinary system pathogens.

Tripleurospermum callosum (Boiss. & Heldr.) E. Hossain was recorded in Turkish ethnobotanical data for its use against urinary and respiratory system ailments. Infusion, decoction and 96% ethanol extracts of T. callosum aerial parts were prepared for in vitro antimicrobial activity against urinary system pathogens Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, Klebsiella aerogenes ATCC 1348 and Candida albicans ATCC 10231. The non-toxic concentrations of extracts and in vivo antimicrobial assay were performed using C. elegans. The extracts were analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS) for phytochemical composition. The water extracts were non-toxic at between 5000 and 312 µg/mL, while 96% ethanol extract at 312 µg/mL for C. elegans. The infusion extract showed in vivo anti-infective effect 5000-312 µg/mL against Gram-negative strains. The results indicate a potential role of plant extracts with relatively non-toxic and anti-infective effects against urinary system pathogens.

In Vitro Antiviral Evaluations of Coldmix®: An Essential Oil Blend against SARS-CoV-2.

Coldmix® is a commercially available Eucalyptus aetheroleum and, Abies aetheroleum blend for medicinal applications. In this present study, the in vitro antiviral potential of Coldmix®, and its major constituents 1,8-cineole and α-pinene were evaluated by using the in vitro ACE2 enzyme inhibition assay as well as the direct contact test against SARS-CoV-2. The observed ACE2 enzyme inhibitory activity of Coldmix®, 1,8-cineole, and α-pinene were 72%, 88%, and 80%, respectively; whereas in the direct contact test in the vapor phase, the destruction of the virus was 79.9% within 5 min and 93.2% in the 30th min, respectively. In a similar Coldmix® vapor phase setup using the in vitro cytotoxicity cell assay, E6 VERO healthy cells were experimentally not affected by toxicity. According to the promising initial antiviral results of Coldmix® and the individually tested constituents, detailed further in vivo evaluation using different virus classes is suggested.

Binary Synergistic Combinations of Lavender and Fennel Essential Oils with Amoxicillin.

Microbial resistance is an important problem in modern healthcare systems. In addition to drug resistance, the side effects of current antibiotic applications are also known issues. In this present study, binary combinations of amoxicillin with European Pharmacopoeia quality lavender (Lavandula angustifolia) and fennel (Foeniculum vulgare) essential oils were evaluated against human pathogenic microbial strains. The checkerboard method was used to quantify the efficacy of the essential oils in combination with amoxicillin. As an initial result, remarkable in vitro antimicrobial activity was observed at relatively low amoxicillin concentrations using different oil combinations against Staphylococcus aureus ATCC 6538, Enterococcus faecalis ATCC 29212, Bacillus cereus ATCC 14579, Escherichia coli NRRL B-3008, Salmonella typhi (clinical isolate), respectively. Fractional inhibitory concentrations were calculated and interpreted in terms of addition, synergy, antagonism, or indifferent. A synergistic interaction with the combination F. vulgare essential oil and amoxicillin (fractional inhibitory concentration index = 8.05 × 10-4) was observed against the pathogens E. faecalis and Escherichia coli. Both essential oils together and in combination with amoxicillin showed a synergistic effect with possible future applications.

In Vitro and In Silico Evaluation of ACE2 and LOX Inhibitory Activity of Origanum Essential Oils and Carvacrol.

Origanum spp. are used both for culinary purposes and for their biological activities. In this study, commercial Origanum majorana, Origanum minutiflorum, Origanum vulgare, and Origanum onites essential oils and their prominent constituent carvacrol were evaluated for their in vitro and in silico angiotensin-converting enzyme 2 and lipoxygenase enzyme inhibitory potentials. The essential oils were analysed by gas chromatography-flame ionisation detection and gas chromatography-mass spectrometry, where carvacrol was identified as the major component (62 - 81%), confirming the quality. In vitro enzyme inhibition assays were conducted both with the essential oils (20 µg/mL) and with carvacrol (5 µg/mL). The comparative values of angiotensin-converting enzyme 2 percent inhibition for O. majorana, O. minutiflorum, O. vulgare, and O. onites essential oils were determined as 85.5, 79.1, 74.3, and 42.8%, respectively. As a result of the enzyme assays, carvacrol showed 90.7% in vitro angiotensin-converting enzyme 2 inhibitory activity. The in vitro lipoxygenase inhibition of the essential oils (in the same order) was 89.4, 78.9, 81.1, and 73.5%, respectively, where carvacrol showed 74.8% inhibition. In addition, protein-ligand docking and interaction profiling was used to gain structural and mechanistic insights into the angiotensin-converting enzyme 2 and lipoxygenase inhibitory potentials of major Origanum essential oil constituents. The in silico findings agreed with the significant enzyme inhibition activity observed in vitro. Further in vivo studies are suggested to confirm the safety and efficacy of the oils.

Chemical Characterization and Multidirectional Biological Effects of Different Solvent Extracts of Arum elongatum: in Vitro and in Silico Approaches.

Arum elongatum (Araceae) is widely used traditionally for the treatment of abdominal pain, arterial hypertension, diabetes mellitus, rheumatism and hemorrhoids. This study investigated the antioxidant properties, individual phenolic compounds, total phenolic and total flavonoid contents (HPLC/MS analysis), reducing power and metal chelating effects of four extracts obtained from A. elongatum (ethyl acetate (EA), methanol (MeOH), methanol/water (MeOH/water) and infusion). The inhibitory activity of the extracts were also determined against acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase and glucosidase enzymes. The MeOH/water extracts contained the highest amount of phenolic contents (28.85 mg GAE/g) while the highest total flavonoid content was obtained with MeOH extract (36.77 mg RE/g). MeOH/water demonstrated highest antioxidant activity against DPPH⋅ radical at 38.90 mg Trolox equivalent per gram. The infusion extract was the most active against ABTS+ ⋅ (133.08 mg TE/g). MeOH/water extract showed the highest reducing abilities with the CUPRAC value of 102.22 mg TE/g and the FRAP value of 68.50 mg TE/g. A strong metal chelating effect was observed with MeOH/water extract (35.72 mg EDTAE/g). The PBD values of the extracts ranged from 1.01 to 2.17 mmol TE/g. EA extract displayed the highest inhibitory activity against AChE (2.32 mg GALAE/g), BChE (3.80 mg GALAE/g), α-amylase (0.56 mmol ACAE/g) and α-glucosidase (9.16 mmol ACAE/g) enzymes. Infusion extract was the most active against tyrosinase enzyme with a value of 83.33 mg KAE/g. A total of 28 compounds were identified from the different extracts. The compounds present in the highest concentration were chlorogenic acids, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, isoquercitrin, delphindin 3,5-diglucoside, kaempferol-3-glucoside and hyperoside. The biological activities of A. elongatum extracts could be due to the presence of compounds such as gallic acid, chlorogenic acids, ellagic acid, epicatechin, catechin, kaempferol, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, quercetin, isoquercitrin, and hyperoside. Extracts of A. elongatum showed promising biological activities which warrants further investigations in an endeavor to develop biopharmaceuticals.

Comparison of marginal and internal adaptation of three-unit fixed dental prostheses made using CAD/CAM metal-free materials.

The aim of this study was to compare the marginal and internal adaptation of three-unit fixed dental prostheses (FDPs) fabricated from different metal-free materials using CAD/CAM methods. A total of 100 three-unit FDPs were produced from a cubic zirconia, a fiber-reinforced resin composite, a polyetheretherketone (PEEK), a polyetherketoneketone (PEKK), and a polymer composite material by the CAD/CAM method (n = 20 per material). The zirconia group was considered the control/reference material. Marginal and internal gap values of the produced FDPs were measured using the silicone replica method at ×40 magnification under a stereomicroscope. The obtained data were analyzed using one-way ANOVA and Tukey's HSD tests. The marginal and internal gap values for the cubic zirconia material were found to be statistically significantly lower than those seen for the PEEK, polymer composite, PEKK, and fiber-reinforced resin composite materials. While the marginal and internal adaptation of the cubic zirconia material was found to be better than the others, it should be noted that the marginal and internal gap values for all other materials tested were found to be within the clinically acceptable range.

Effect of Extraction Time on Origanum onites L. Infusions and Essential Oils - Biological Evaluation, Statistical Principal Component and Hierarchial Cluster Analyses.

Origanum onites L. of Lamiaceae, is used as a culinary spice and herbal tea; also for its antioxidant, antimicrobial effects among other activities and effects. This research aims to examine the in vitro antimicrobial and antioxidant activities of the infusions and the essential oils (EOs) obtained using different conditions from the aerial parts of the processed and raw of O. onites herbal material. The EOs from O. onites were distilled at different times and characterized both by GC-FID and GC/MS systems. The resulting main compounds were identified as carvacrol (65.5-91 %), linalool (0.3-17.9 %), γ-terpinene (2.8-4.6 %), and thymol (0.5-1.5 %), respectively. In addition, Origanum infusions were prepared at four different time intervals, where the volatile compounds of the infusions were analysed using the HS-SPME-GC/MS system. Statistical Principal Component (PCA) and Hierarchical Cluster Analyses (HCA) tools were used to demonstrate the composition variations on different times for O. onites infusion and EO samples.

Mechanical analysis of three-unit metal-free fixed dental prostheses produced in different materials with CAD/CAM technology.

OBJECTIVES: The aim of this study was to evaluate the mechanical analysis of different three-unit metal-free fixed dental prostheses (FDPs) produced by computer-aided design (CAD)/computer-aided manufacturing (CAM). MATERIALS AND METHODS: A hundred stainless steel die models of a mandibular left first premolar and a mandibular left first molar were prepared. The specimens were divided into five CAD/CAM material groups (n = 20): Group ZIR, a cubic zirconia (DD cube ONE®); Group FRC, FRC resin material (Trinia); Group PEEK, a PEEK material (KERA® starPEEK); Group PEKK, a PEKK material (Pekkton® ivory); and Group COMP, a polymer composite material (BreCAM.HIPC). Compression test was applied to the specimens, and then the results were analyzed statistically using one-way ANOVA and Tukey's tests. In addition, deformation analyses in FDPs were compared with finite element method (FEM). After the compression test, the damage to FDPs was evaluated with a scanning electron microscopy. RESULTS: Although ZIR (2461 ± 93.70 N) showed high fracture load values, FRC (1571 ± 35.96 N) material was found to be advantageous in terms of toughness. These were followed by PEEK (1398 ± 38.26 N), PEKK (1227 ± 44.25 N), and COMP (829 ± 32.33 N), respectively. A ductile fracture was observed in PEEK, PEKK, and FRC due to their elastic structures. The deformation properties examined by the FEM were found to be similar to the compression test. CONCLUSIONS: CAD/CAM high-performance polymers and cubic zirconia material can be used in three-unit FDPs. In three-unit FDPs, the use of FRC material can be advantageous due to both biomechanics and lightness. CLINICAL RELEVANCE: Metal-free CAD/CAM materials may offer new possibilities in three-unit FDPs.

Effect of unfiltered cigarettes on marginal bone loss of dental implants: A single center 4-year retrospective clinical study.

PURPOSE: This retrospective clinical study evaluated, by radiographic analysis, the effect of unfiltered and filtered tobacco cigarette smoking on marginal bone loss (MBL) in the subjects with dental implants. METHODS: In a 4-year retrospective clinical study, 419 dental implants were placed in 188 subjects aged 23-76 years who underwent implant-supported fixed prosthetic restorations. The effects of gender, implant length, implant diameter, implant location, and use of unfiltered and filtered tobacco cigarettes on marginal bone were investigated. MBL was analyzed on the mean, mesial, and distal surfaces of dental implants on periapical radiographs. The results of the data were statistically analyzed with ANOVA and Tukey test. RESULTS: A significant correlation was found between MBL difference and gender, implant length, and implant location (P< 0.05). Smokers had significantly higher MBL than nonsmokers, both within and between groups (P< 0.05). There was a significant difference in MBL in the mesial region in unfiltered cigarette smokers compared to filtered cigarette smokers (P= 0.013). There was a significant increase in MBL in the mesial and distal region compared to heavy smokers of cigarettes without filters (>20 cigarettes/day) and heavy smokers of cigarettes with filters (>20 cigarettes/day) (P< 0.05). CLINICAL SIGNIFICANCE: In this study, tobacco smoking had a negative effect on marginal bone loss. There was a significant increase in marginal bone loss on the mesial and distal surfaces, especially in unfiltered heavy tobacco smokers (>20 cigarettes/day).

Fracture strength of different veneers on polyetheretherketone (PEEK) frameworks in implant-supported single crowns.

PURPOSE: To evaluate the fracture strength of polyetheretherketone (PEEK) single crowns veneered with different materials produced by computer-aided design (CAD)-computer-aided manufacture (CAM) after aging. METHODS: 60 stainless-steel master dies were prepared with a 1 mm-wide deep chamfer. Sixty PEEK frameworks were produced with a CAD-CAM system for the right maxillary first molar tooth on the dies. PEEK frameworks were divided into six groups (n= 10) according to veneering materials (five CAD-CAM materials and a resin composite). Group ZR: monolithic zirconia (Upcera ST-Color); Group EC: lithium disilicate glass-ceramic (IPS e.max CAD); Group LU: resin nano-ceramic (Lava Ultimate); Group VM: feldspathic ceramic (Vitablocs Mark II); Group VS: zirconia-reinforced lithium silicate glass-ceramic (VITA Suprinity); and Group CR: indirect resin composite (Gradia). All samples were subjected to a fracture strength test in a universal test device after thermo-mechanical aging and then the results were analyzed statistically using one-way ANOVA and Tukey's post hoc test. In addition, post-fracture analyses of all samples were performed with a stereomicroscope. RESULTS: The differences in fracture strength values of different veneer materials in single crowns with a PEEK framework were statistically significant (P< 0.05). Fracture strength was highest in Group ZR (1665 N), followed by Groups LU (1440 N), EC (1249 N), CR (918 N), VS (754 N), and VM (655 N). CLINICAL SIGNIFICANCE: PEEK frameworks may have the potential to be used with many veneer materials of different content and properties in fixed partial prostheses.

Effect of ultrasonic scaling and air polishing on the surface roughness of polyetheretherketone (PEEK) materials.

PURPOSE: To evaluate the effects of ultrasonic scaling (US) and air polishing (AP) on four polyetheretherketone (PEEK) composites. METHODS: One hundred-twenty 15 × 3 mm discs of PEEK specimens were divided into four groups (n=30): Unfilled PEEK(U-PEEK), carbon fiber-reinforced PEEK(CFR-PEEK), glass fiber-reinforced PEEK(GFR-PEEK), and ceramic-filled PEEK(CF-PEEK). Each group was further divided into three subgroups (n = 10): control, US, and AP. Profilometry and scanning electron microscopy were used to analyze and evaluate surface roughness (SR). Statistical analyses of the data obtained were conducted using Shapiro-Wilk, Welch, and Games-Howell tests. RESULTS: When the SR values of the specimens with US cleaning were evaluated, a statistically significant difference was found between the groups (P< 0.05). When the SR values of the specimens with AP cleaning were analyzed, there was a statistically significant difference in the CF-PEEK group (P< 0.05), whereas the other groups were not significantly different (P> 0.05). More studies are needed on CFR-PEEK and GFR-PEEK materials offered as alternatives to CF-PEEK in dentistry. CLINICAL SIGNIFICANCE: Dental instruments affect the different PEEK materials, as well as causing surface roughness in many restorative materials used in dentistry. Surface roughness that occurs in dental restorations can cause bacterial adhesion. It is clinically important to choose the dental instrument according to the type of PEEK used for dental implant or prosthetic restoration in the clinic.

Biomechanical and Biochemical Analyses of the Effects of Propranolol on the Osseointegration of Implants.

ABSTRACT: This study aimed to investigate the effects of systemic propranolol on the osseointegration of titanium implants. After the surgical insertion of titanium implants into the metaphyseal part of the tibiae of rats, the rats were randomly divided into three equal groups: the control (n = 8), propranolol dosage-1 (PRP-1) (n = 8), and propranolol dosage-2 (PRP-2) (n = 8) groups. In the control group, the rats received no further treatment during the 4-week experimental period after the surgery. After the surgical insertion of the implants, the rats in the PRP-1 and PRP-2 groups were given 5 mg/kg and 10 mg/kg propranolol, respectively, every 3 days for the 4-week experimental period. After the experimental period, the rats were euthanized. Blood sera were collected for biochemical analysis, and the implants and surrounding bone tissues were used for the biomechanical reverse torque analysis. One-way ANOVA and Tukey's honest significant difference test were used for statistical analysis. The student t-test was used to analyze the data obtained from the tests and the controls. There were no significant differences in the reverse torque analysis results and the biochemical parameters (alkaline phosphatase, calcium, and phosphorus) of the groups (P > 0.05). Alkaline phosphatase was, however, found to be higher in test animals compared to the controls (P < 0.05). Also, propranolol did not biomechanically affect the osseointegration of titanium implants, while alkaline phosphatase activity was higher in the test animals.

Chemical Characterization and Biological Activity of the Mastic Gum Essential Oils of Pistacia lentiscus Var. Chia from Turkey.

The essential oils (EOs) were isolated by hydrodistillation from wild and cultivated Pistacia lentiscus L. var. chia-mastic gum tree (Anacardiaceae) from two natural habitats, namely from Cesme-Uzunkoy (1) and Mordogan (2), and one cultivated source, Cesme-Germiyan (3), in Izmir, Turkey. This comparative study evaluated the chemical composition and biological activity of mastic gum essential oils (MGEOs). For this purpose, MGEOs 1-3 were analyzed by gas chromatography-flame ionization detection (GC-FID), gas chromatography-mass spectrometry (GC-MS), and chiral GC for α-pinene. Laboratory assays were conducted to assess for potential in vitro cytotoxicity (multiple in vitro cancer cell lines), antimicrobial properties (five bacterial species and yeast), anti-inflammatory activity (inhibition of inducible nitric oxide synthase, iNOS), and the attraction of Ceratitis capitata (Mediterranean fruit fly, medfly), respectively. Chemical analysis indicated that MGEOs 1 and 2 were rich in α-pinene (56.2% and 51.9%), myrcene (20.1% and 18.6%), and ß-pinene (2.7% and 3.1%), respectively; whereas MGEO-3 was characterized by a high level of α-pinene (70.8%), followed by ß-pinene (5.7%) and myrcene (2.5%). Chiral GC analyses showed that concentration ratios between (-)/(+)-α-pinene and (-)-α-pinene/myrcene allowed for differentiation between wild and cultivated MGEO sources. In biological assays, MGEOs 1-3 did not exhibit significant antimicrobial effects against the pathogens evaluated and were not strong attractants of male medflies; however, all three MGEOs displayed a dose-dependent inhibition of iNOS, and MGEOs 1 and 2 exhibited selective in vitro cytotoxicity against human cancer cells. These results suggest that wild-type mastic gum oils from Cesme and Mordogan (MGEOs 1 and 2) are potential sources of beneficial products and warrant further investigation.

In Vivo Wound Healing and In Vitro Anti-Inflammatory Activity Evaluation of Phlomis russeliana Extract Gel Formulations.

The air-dried aerial parts of Phlomis russeliana (Sims) Lag. Ex Benth. was extracted by methanol and fractionated by n-hexane, dichloromethane, and ethyl acetate, respectively. The wound healing properties of P. russeliana extract gel was evaluated using the in vivo excisional wound model using Balb-c mice. Initially, the P. russeliana methanol extract showed LOX inhibitory activity at IC50 = 23.2 µg/mL, whereas the DPPH• assay showed IC50 = 0.89 mg/mL, and the ABTS• assay showed IC50 = 0.99 mg/mL, respectively. In addition, a remarkable anti-inflammatory activity was observed in the cell culture assay. Thereafter, activity-guided fractionation was performed by LOX enzyme inhibition assays, and the structures of the two most active fractions were revealed by both GC-FID and GC/MS analyses, simultaneously. Phytol and 1-heptadecanoic acid were characterized as the active constituents. Moreover, the P. russeliana extract gel formulation was applied for in vivo tests, where the new gel formulation supported the in vitro anti-inflammatory activity findings. As a conclusion, this experimental results support the wound healing evidence based on the ethnobotanical application of Phlomis species with further potential.

Rutamarin: Efficient Liquid-Liquid Chromatographic Isolation from Ruta graveolens L. and Evaluation of Its In Vitro and In Silico MAO-B Inhibitory Activity.

Naturally occurring coumarins are a group of compounds with many documented central nervous system (CNS) activities. However, dihydrofuranocoumarins have been infrequently investigated for their bioactivities at CNS level. Within the frame of this study, an efficient liquid-liquid chromatography method was developed to rapidly isolate rutamarin from Ruta graveolens L. (Rutaceae) dichloromethane extract (DCM). The crude DCM (9.78 mg/mL) and rutamarin (6.17 M) were found to be effective inhibitors of human monoamine oxidase B (hMAO-B) with inhibition percentages of 89.98% and 95.26%, respectively. The inhibitory activity against human monoamine oxidase A (hMAO-A) for the DCM extract was almost the same (88.22%). However, for rutamarin, it significantly dropped to 25.15%. To examine the molecular interaction of rutamarin with hMAO- B, an in silico evaluation was implemented. A docking study was performed for the two enantiomers (R)-rutamarin and (S)-rutamarin. The (S)-rutamarin was found to bind stronger to the hMAO-B binging cavity.

Antiprotozoal Activity of Turkish Origanum onites Essential Oil and Its Components.

Essential oil of Origanum species is well known for antimicrobial activity, but only a few have been evaluated in narrow spectrum antiprotozoal assays. Herein, we assessed the antiprotozoal potential of Turkish Origanum onites L. oil and its major constituents against a panel of parasitic protozoa. The essential oil was obtained by hydrodistillation from the dried herbal parts of O. onites and analyzed by Gas Chromatography-Flame Ionization Detector (GC-FID) and Gas Chromatography coupled with Mass Spectrometry (GC-MS). The in vitro activity of the oil and its major components were evaluated against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. The main component of the oil was identified as carvacrol (70.6%), followed by linalool (9.7%), p-cymene (7%), γ-terpinene (2.1%), and thymol (1.8%). The oil showed significant in vitro activity against T. b. rhodesiense (IC50 180 ng/mL), and moderate antileishmanial and antiplasmodial effects, without toxicity to mammalian cells. Carvacrol, thymol, and 10 additional abundant oil constituents were tested against the same panel; carvacrol and thymol retained the oil's in vitro antiparasitic potency. In the T. b. brucei mouse model, thymol, but not carvacrol, extended the mean survival of animals. This study indicates the potential of the essential oil of O. onites and its constituents in the treatment of protozoal infections.

Anti-inflammatory and antibacterial evaluation of Thymus sipyleus Boiss. subsp. sipyleus var. sipyleus essential oil against rhinosinusitis pathogens.

Thymus sipyleus Boiss. subsp. sipyleus var. sipyleus of the Lamiaceae, locally known as thyme scented lemon, which is an endemic taxon collected from Sivas in Anatolia, was investigated in this study due to its folk medicine use against rhinosinusitis. The aromatic characteristics of the plant material gave the idea for the detailed evaluation of the volatiles and essential oil thereof. Consequently, the oil was obtained by Clevenger type hydrodistillation followed by gas chromatography-flame ionization detector (GC-FID) and gas chromatography/mass spectrometry (GC/MS) analyses for phytochemical characterization. To confirm the folk medicinal use against sinusitis, in vitro antimicrobial activities of the essential oil was evaluated by agar diffusion, microdilution and vapour diffusion methods against selected rhinosinusitis associated strains such as Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis, Streptococcus pyogenes, S. pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae and Moraxella catarrhalis. Additionally, the in vitro anti-inflammatory activity was evaluated by 5-lipoxygenase (5-LOX) inhibitory effect of the essential oil spectrophotometrically. Furthermore, the composition of the volatiles of the vapour phase of the oil was determined by headspace-solid phase microextraction (HS-SPME-GC/MS) after 15 min and 24 h in accordance with antimicrobial vapour diffusion method conditions, respectively. According to the analytical results, the main component was determined as thymol (66.2%). Whereas in the HS-SPME method p-cymene (26.1%) and γ-terpinene (26%) were identified as the main volatile components within the 15. min., and thymol (75.3%) after 24 h, respectively. The antibacterial activity against rhinosinusitis pathogens varied between 160 and 1250 µg/mL minimum inhibitory concentrations, with the best inhibitory effects observed against the S. aureus, S. pyogenes and M. catarrhalis. The anti-inflammatory activity of the oil was determined as 12.1 ±â€¯1.8% in 100 µg/mL. The results showed the in vitro antimicrobial and anti-inflammatory potential of the oil also in vapour phase against sinusitis supporting the traditional use.

Antibacterial profiling of abietane-type diterpenoids.

Abietic and dehydroabietic acid are interesting diterpenes with a highly diverse repertoire of associated bioactivities. They have, among others, shown antibacterial and antifungal activity, potentially valuable in the struggle against the increasing antimicrobial resistance and imminent antibiotic shortage. In this paper, we describe the synthesis of a set of 9 abietic and dehydroabietic acid derivatives containing amino acid side chains and their in vitro antimicrobial profiling against a panel of human pathogenic microbial strains. Furthermore, their in vitro cytotoxicity against mammalian cells was evaluated. The experimental results showed that the most promising compound was 10 [methyl N-(abiet-8,11,13-trien-18-yl)-d-serinate], with an MIC90 of 60µg/mL against Staphylococcus aureus ATCC 25923, and 8µg/mL against methicillin-resistant S. aureus, Staphylococcus epidermidis and Streptococcus mitis. The IC50 value for compound 10 against Balb/c 3T3 cells was 45µg/mL.

Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9.

Matrix metalloproteinases (MMPs) are important proteases involved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have been reported as potential diagnostic and prognostic biomarkers in many types of cancer. New oxadiazole, thiadiazole, and triazole derivatives were synthesized and evaluated for their anticancer effects on A549 human lung adenocarcinoma and C6 rat glioma cell lines. In order to examine the relationship between their anticancer activity and MMP-9, the compounds were evaluated for their inhibitory effects on MMPs. N-(1,3-Benzodioxol-5-ylmethyl)-2-{[5,[5-(((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)methyl)-1,3,4-oxadiazol-2-yl]thio}acetamide (8) and N-(1,3-benzodioxol-5-ylmethyl)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]acetamide (9) revealed promising cytotoxic effects on A549 and C6 cell lines similar to cisplatin without causing any toxicity towards NIH/3T3 mouse embryonic fibroblast cell line. Compounds 8 and 9 were also the most effective MMP-9 inhibitors in this series. Moreover, docking studies pointed out that compounds 8 and 9 had good affinity to the active site of the MMP-9 enzyme. The molecular docking and in vitro studies suggest that the MMP-9 inhibitory effects of compounds 8 and 9 may play an important role in lung adenocarcinoma and glioma treatment.