Determination of chemical components of the endemic species Allium turcicum L. plant extract by LC-MS/MS and evaluation of medicinal potentials.

The Allium turcicum L. (Zuzubak) plant as a cultivated vegetable have various health benefits and consumed as a food. Due to the shortcoming evidence in literature and the importance of this plant in folk medicine, in the present study, for the first time, we evaluated the bioactive profile of components (using LC-MS/MS), cytotoxicity, anticancer, antioxidant, and antibacterial prospectives of Zuzubak methanol extract. Reported results show that the extract is rich in bioactive compounds and has anticancer activity with breast cancer cells (MCF-7), human prostate cancer cells (DU-145), and Human osteosarcoma cancer Cell lines of (IC50) in dose dependent manner in the concentration range of 31.25 µg/mL and 2000 µg/mL for 24 and 48 h. Western blotting results determined that the extract significantly suppressed the growth of U2OS, MCF-7, and DU-145 cancer cells by down expression of Ang-1 (angiogenic protein) and Beclin-1 (autophagy protein) and overexpression of Bax (a proapoptotic protein). The oxidative stress indices showed a reduction in RPE-1 and MCF-7 cells and an upsurge in U2OS and DU-145 cells. Additionally, the antimicrobial assay showed suppression of the growth of various pathogenic microorganisms in 4.00-8.00 µg/concentrations of Zuzubak extract using the microdilution method. The phytochemicals identified showed promising anticancer, antioxidant effects, and antimicrobial properties, representing a valuable herbal source for drug development studies.

Green Synthesis of Silver Nanoparticles Derived from Papaver rhoeas L. Leaf Extract: Cytotoxic and Antimicrobial Properties.

In the last few decades, the search for metal nanoparticles as an alternative to cancer treatments and antibiotics has increased. In this article, the spectroscopic (ultraviolet-visible (UV-vis), electron-dispersing X-ray (EDX), and Fourier transform infrared (FT-IR)), microscopic (field emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), and atomic force microscope (AFM)), structural (X-ray diffractometer (XRD) and zetasizer), and analytic (thermogravimetric/differential thermal analyzer (TGA-DTA)) characterization of the silver nanoparticles (AgNPs) produced from Papaver rhoeas (PR) L. leaf extract are presented. PR-AgNPs are generally spherical and have a maximum surface plasmon resonance of 464.03 nm. The dimensions of the manufactured nanomaterial are in the range of 1.47-7.31 nm. PR-AgNPs have high thermal stability and a zeta potential of -36.1 mV. The minimum inhibitory concentration (MIC) values (mg L-1) of PR-AgNPs on Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Candida albicans are 1.50, 0.75, 3.00, 6.00, and 0.37, respectively. In the study, the cytotoxic and proliferative effects of PR-AgNPs using the MTT (3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide) method on various cancer cell lines (CACO-2 (human colon adenocarcinoma cell), MCF-7 (human breast cancer cell), T98-G (glioblastoma multiforme cell), and healthy HUVEC (human umbilical vein endothelial cell)) cell lines are presented. After 24 and 48 h of the application, the half-maximum inhibitory concentration (IC50) values (µg mL-1) of PR-AgNPs on HUVEC, CACO-2, MCF-7, and T98-G lines are 2.365 and 2.380; 2.526 and 2.521; 3.274 and 3.318; 3.472 and 3.526, respectively. Comprehensive in vivo research of PR-AgNPs is proposed to reveal their potential for usage in sectors such as nanomedicine and nanochemistry.

Biosynthesis, characterization, and investigation of antimicrobial and cytotoxic activities of silver nanoparticles using Solanum tuberosum peel aqueous extract.

Metallic nanoparticle biosynthesis is thought to offer opportunities for a wide range of biological uses. The green process of turning biological waste into utilizable products gaining attention due to its economical and eco-friendly approach in recent years. This study reported the ability of Solanum tuberosum (ST) peel extract to the green synthesis of non-toxic, stable, small-sized silver nanoparticles without any toxic reducing agent utilizing the phytochemical components present in its structure. UV-visible spectroscopy, X-ray diffraction analysis, Fourier transform infrared spectroscopy, flourier scanning electron microscopy, atomic force microscopy, transmission electron microscopy, and energy dispersive analysis X-ray confirmed the biosynthesis and characterization of silver nanoparticles. Also, dynamic light scattering and thermogravimetric analyses showed stable synthesized nanoparticles. The antibacterial activity of the biosynthesized silver nanoparticles was evaluated against four different bacterial strains, Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus) Bacillus subtilis (B. subtilis), and a yeast, Candida albicans (C. albicans) using the minimum inhibitory concentration technique. The cytotoxic activities were determined against Human dermal fibroblast (HDF), glioblastoma (U118), colorectal adenocarcinoma (CaCo-2), and human ovarian (Skov-3) cell lines cancer cells using MTT test. The nanoparticle capping agents that could be involved in the reduction of silver ions to Ag NPs and their stabilization was identified using FTIR. Nanoparticles were spherical in shape and had a size ranging from 3.91 to 27.07 nm, showed crystalline nature, good stability (-31.3 mV), and the presence of capping agents. ST-Ag NPs significantly decreased the growth of bacterial strains after treatment. The in vitro analysis showed that the ST-Ag NPs demonstrated dose-dependent cytotoxicity against cell lines. Based on the data, it is feasible to infer that biogenic Ag NPs were capped with functional groups and demonstrated considerable potential as antibacterial and anticancer agents for biomedical and industrial applications.

Green synthesis of silver nanoparticles mediated Diospyros kaki L. (Persimmon): determination of chemical composition and evaluation of their antimicrobials and anticancer activities.

The eco-friendly synthesis of metallic nanoparticles (MNPs) using biological materials is an encouraging and innovativeness approach to nanotechnology. Among other synthesizing methods, biological methods are chosen because of their high efficiency and purity in many aspects. In this work, using the aqueous extract obtained from the green leaves of the D. kaki L. (DK); silver nanoparticles were synthesized in a short time and simply with an eco-friendly approach. The properties of the synthesized silver nanoparticles (AgNPs) were characterized using various techniques and measurements. In the characterization data of AgNPs, Maximum absorbance at 453.34 nm wavelengths, the average size distribution of 27.12 nm, the surface charge of -22.4 mV, and spherical appearance were observed. LC-ESI-MS/MS analysis was used to assess the compound composition of D. kaki leaf extract. The chemical profiling of the crude extract of D. kaki leaves revealed the presence of a variety of phytochemicals, predominantly phenolics, resulting in the identification of five major high-feature compounds: two major phenolic acids (Chlorogenic acid and Cynarin), and tree flavonol glucosides (hyperoside, quercetin-3-glucoside, and quercetin-3- D-xyloside). The components with the highest concentrations were cynarin, chlorogenic acid, quercetin-3- D-xyloside, hyperoside, and quercetin-3-glucoside, respectively. Antimicrobial results were determined by a MIC assay. The biosynthesized AgNPs exhibited strong antibacterial activity against the human and food pathogen Gram (+ and -) bacteria and good antifungal activity against pathogenic yeast. It was determined that 0.03-0.050 µg/mL concentrations ranges of DK-AgNPs were growth suppressive concentrations on all pathogen microorganisms. The MTT technique was used to study the cytotoxic effects of produced AgNPs on cancer cell lines (Glioblastoma (U118), Human Colorectal Adenocarcinoma (Caco-2), Human Ovarian Sarcoma (Skov-3) cancer cell lines, and Human Dermal Fibroblast (HDF) healthy cell line). It has been observed that they have a suppressive effect on the proliferation of cancerous cell lines. After 48 h of treatment with Ag-NPs, the DK-AgNPs were found to be extremely cytotoxic to the CaCo-2 cell line, inhibiting cell viability by up to 59.49% at a concentration of 50 g mL-1. It was found that the viability was inversely related to the DK-AgNP concentration. The biosynthesized AgNPs had dose-dependent anticancer efficacy. Because of the high concentration of bioactive chemicals in Diospyros kaki, it may be employed as a biological resource in medicinal applications. DK-AgNPs were shown to be an effective antibacterial agent as well as a prospective anticancer agent. The results provide a potential approach for the biogenic production of DK-AgNPs utilizing D. kaki aqueous leaf extract.

The Investigation of the Chemical Composition and Applicability of Gold Nanoparticles Synthesized with Amygdalus communis (Almond) Leaf Aqueous Extract as Antimicrobial and Anticancer Agents.

The current work's main objective was to determine the chemical composition of Amygdalus communis (AC) leaf extract and examine the antibacterial and cytotoxic properties of biosynthesized gold nanoparticles (AuNPs). The chemical composition of AC leaf extract was determined using LC-ESI/MS/MS to detect compounds that may be responsible for the reducing, stabilizing, and capping steps in the synthesis of nanoparticles and their biological activities. The AC-AuNPs were spherical, with a particle size lower than 100 nm and a face-centered cubic structure. The EDX spectrum confirmed the formation of AuNPs and a negative zeta potential value (-27.7 mV) suggested their physicochemical stability. The in vitro cytotoxic efficacy of the AC-AuNPs against colorectal adenocarcinoma (Caco-2), glioma (U118), and ovarian (Skov-3) cancer cell lines and human dermal fibroblasts (HDFs) was evaluated by MTT assay. CaCo-2 cell proliferation was effectively inhibited by the AC-AuNPs at concentrations between 25 and 100 g mL-1. The AC-AuNPs exerted preeminent antimicrobial activity against Bacillus subtilis with an MIC of 0.02 µg/mL, whilst good activity was shown against Staphylococcus aureus bacteria and Candida albicans yeast with an MIC of 0.12 µg/mL. Ultimately, the results support the high antibacterial and anticancer potential of biosynthesized AuNPs from AC leaf extract.

Green Synthesis of Silver Nanoparticles from Allium cepa L. Peel Extract, Their Antioxidant, Antipathogenic, and Anticholinesterase Activity.

The present work deals with the green synthesis and characterization of silver nanoparticles (AgNPs) using Allium cepa (yellowish peel) and the evaluation of its antimicrobial, antioxidant, and anticholinesterase activities. For the synthesis of AgNPs, peel aqueous extract (200 mL) was treated with a 40 mM AgNO3 solution (200 mL) at room temperature, and a color change was observed. In UV-Visible spectroscopy, an absorption peak formation at ~439 nm was the sign that AgNPs were present in the reaction solution. UV-vis, FE-SEM, TEM, EDX, AFM, XRD, TG/DT analyses, and Zetasizer techniques were used to characterize the biosynthesized nanoparticles. The crystal average size and zeta potential of AC-AgNPs with predominantly spherical shapes were measured as 19.47 ± 1.12 nm and -13.1 mV, respectively. Pathogenic microorganisms Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were used for the Minimum Inhibition Concentration (MIC) test. When compared to tested standard antibiotics, AC-AgNPs demonstrated good growth inhibitory activities on P. aeuruginosa, B. subtilis, and S. aureus strains. In vitro, the antioxidant properties of AC-AgNPs were measured using different spectrophotometric techniques. In the ß-Carotene linoleic acid lipid peroxidation assay, AC-AgNPs showed the strongest antioxidant activity with an IC50 value of 116.9 µg/mL, followed by metal-chelating capacity and ABTS cation radical scavenging activity with IC50 values of 120.4 µg/mL and 128.5 µg/mL, respectively. The inhibitory effects of produced AgNPs on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were determined using spectrophotometric techniques. This study provides an eco-friendly, inexpensive, and easy method for the synthesis of AgNPs that can be used for biomedical activities and also has other possible industrial applications.

Green synthesis of silver nanoparticles based on the Raphanus sativus leaf aqueous extract and their toxicological/microbiological activities.

Silver nanoparticles (AgNPs) have several uses. Many scientists are working on producing AgNPs from plant extracts for use as biomedicines against drug-resistant bacteria and malignant cell lines. In the current study, plant-based AgNPs were synthesized using Raphanus sativus L. (RS) leaf aqua extract. Different concentrations of AgNO3 were used to optimize the synthesis process of RS-AgNPs from the aqueous leaf extract. Energy-dispersive X-ray analysis (EDX), transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscope (AFM), and UV-vis spectroscopy were used to analyze the generated materials. Furthermore, to evaluate the biological properties of the obtained materials, Bacillus subtilis (B. subtilis), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Candida albicans (C. albicans) pathogen strains were used for the minimum inhibitory concentration (MIC) assays. Subsequently, healthy cell lines (human dermal fibroblast (HDF)) and cancerous cell lines (glioma/U118, Ovarian/Skov-3, and colorectal adenocarcinoma/CaCo-2) were engaged to determine the cytotoxic effects of the synthesized NPs. The cytotoxic and anti-pathogenic potential of AgNPs synthesized by the proposed green approach was investigated. The results were encouraging compared to the standards and other controls. Plant-based AgNPs were found to be potential therapeutic agents against the human colon cancer cell (CaCo-2) and showed strong inhibitory activity on Candida albicans and Staphylococcus aureus growth. The RS-AgNPs generated have highly effective antimicrobial properties against pathogenic bacteria. Our findings also show that green RS-AgNPs are more cytotoxic against cancerous cell lines than normal cell lines. Synthesized nanoparticles with desirable morphology and ease of preparation are thought to be promising materials for antimicrobial, cytotoxic, and catalytic applications.

Analysis of bioactive compounds using LC-ESI-MS/MS, cytotoxic, antimicrobial effects, and enzyme activities from Cyclotrichium origanifolium.

Cyclotrichium origanifolium is a medicinal plant belonging to the Lamiaceae family. In this study, phenolic content analysis, antimicrobial effects, and cytotoxic effects of extracts of C. origanifolium were investigated. In the extracts, phenolic compound analysis by the liquid chromatography-electrospray ionization-tandem mass spectrometry method, antimicrobial effect by the minimum inhibition concentration method, and cytotoxic effect on human dermal fibroblasts (HDF), glioblastoma cell (U87), ovarian adenocarcinoma cell (Skov-3), and human colorectal adenocarcinoma cell (CaCo-2) cancer cell lines were investigated. Cytotoxicity analyses were performed by the MTT method. In addition, the GST and AChE enzyme activities of the extracts were also measured. Around 18 compounds were detected in both the methanol and ethanol extract. It was found that the best antimicrobial effect on Gram-negative Pseudomonas aeruginosa was on methanol extract, while the ethanol extract was on Candida albicans fungus (respectively, 2.50 mg/ml, 5.0 µg/ml). A 500 µg/ml of methanol extract has been shown to have cytotoxic activity high effect on HDF cells. GST and AChE activity were found to decrease in a concentration-dependent manner.

Antioxidant, AChE inhibitory, and anticancer effects of Verbascum thapsus extract.

Verbascum thapsus (VT) is a medicinal plant that is used in folk medicine to treat a variety of ailments. For this study, the biological functions of VT methanol extract were determined in vitro. The plant's methanol extract was created through the maceration process. The phytochemical composition of plant extracts was investigated using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The antioxidant capacity of the extract was determined using the DPPH (2,2-diphenyl-1-picrylhydrazil) and ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) tests and its cytotoxicity was assessed using the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole)) assay on the Caco-2 (human colorectal adenocarcinoma cells), LNCaP (Lymph Node Carcinoma of the Prostate), and HEK293 cell lines (Human embryonic kidney 293 cells) used to model colon, prostate, and non-cancerous cells. VT extract showed low DPPH and ABTS radical scavenging activities compared to standard antioxidants at 30 mg/ml concentration. In addition, it was determined that VT extract inhibited acetylcholinesterase enzyme.

Investigation of Antimicrobial and Cytotoxic Properties and Specification of Silver Nanoparticles (AgNPs) Derived From Cicer arietinum L. Green Leaf Extract.

Using biological materials to synthesize metallic nanoparticles has become a frequently preferred method by researchers. This synthesis method is both fast and inexpensive. In this study, an aqueous extract obtained from chickpea (Cicer arietinum L.) (CA) leaves was used in order to synthesize silver nanoparticles (AgNPs). For specification of the synthesized AgNPs, UV-vis spectrophotometer, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), electron dispersive X-ray (EDX), and zeta potential (ZP) analyses data were used. Biologically synthesized AgNPs demonstrated a maximum surface plasmon resonance of 417.47 nm after 3 h. With the powder XRD model, the mean crystallite dimension of nanoparticles was determined as 12.17 mm with a cubic structure. According to the TEM results, the dimensions of the obtained silver nanoparticles were found to be 6.11-9.66 nm. The ZP of the electric charge on the surface of AgNPs was measured as -19.6 mV. The inhibition effect of AgNPs on food pathogen strains and yeast was determined with the minimum inhibition concentration (MIC) method. AgNPs demonstrated highly effective inhibition at low concentrations especially against the growth of B. subtilis (0.0625) and S. aureus (0.125) strains. The cytotoxic effects of silver nanoparticles on cancerous cell lines (CaCo-2, U118, Sk-ov-3) and healthy cell lines (HDF) were revealed. Despite the increase of AgNPs used against cancerous and healthy cell lines, no significant decrease in the percentage of viability was detected.

Spectroscopic and molecular modeling methods to investigate the interaction between psycho-stimulant modafinil and calf thymus DNA using ethidium bromide as a fluorescence probe.

Interaction type of modafinil with calf thymus DNA (ct-DNA) was examined systematically using ethidium bromide (EB) as a fluorescence probe by fluorescence spectroscopy, UV-Vis spectroscopy, viscosity and molecular docking method. The fluorescence quenching mechanism of ct-DNA-EB by modafinil can be combination of static and dynamic quenching. Results of UV-Vis absorption, competitive binding with Hoechst 33258, ionic strength effect studies, viscosity measurements were confirmed that the interaction type of modafinil with ct-DNA was intercalation. According to docking studies R-modafinil showed better interaction with ct-DNA which is consistent with known pharmacological properties of modafinil. The calculated thermodynamic parameters, enthalpy and entropy change, suggested that the driven forces are hydrogen bonding or van der Walls forces. Results of the docking studies were compatible with the experimental results and confirmed the hydrogen bond formation between modafinil and ct-DNA.

Ecofriendly Synthesis of Silver Nanoparticles Using Ananas comosus Fruit Peels: Anticancer and Antimicrobial Activities.

Metallic nanoparticles are valuable materials and have a range of uses. Nanoparticles synthesized from plant wastes by environment-friendly methods have attracted the attention of researchers in recent years. Also, the advantages of biological resources and synthesis methods are attracting attention. In this study, silver nanoparticles were synthesized from Ananas comosus fruit peels using ecofriendly method steps. The characterization of the particles obtained was determined by using a UV-visible spectrophotometer (UV-Vis.), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction diffractometer (XRD), Fourier scanning electron microscope (FESEM), and transmission electron microscopy (TEM). The nanoparticles showed maximum absorbance at 463 nm, measuring 11.61 in crystal nanosize, and presented spherical in appearance. An antimicrobial activity test was determined with the minimum inhibition concentration (MIC) method. The nanoparticles showed promising inhibitory activity on the Gram-positive and Gram-negative pathogen microorganisms (Escherichia coli ATCC25922, Staphylococcus aureus ATCC29213, Bacillus subtilis ATCC11774, Pseudomonas aeruginosa ATCC27833 bacteria, and Candida albicans yeast) at low concentrations. The cytotoxic and growth inhibitory effects of silver nanoparticles on different cancer cell lines were examined via the MTT assay.

Multispectroscopic and Computational Investigation of ct-DNA Binding Properties with Hydroxybenzylidene Containing Tetrahydrocarbazole Derivative.

Mode of interaction of a new tetrahydrocarbazole derivative with ct-DNA has been investigated systematically using fluorescence spectroscopy, UV-Vis spectroscopy and circular dichroism spectroscopy. It is concluded that TAH could intercalate into the base pairs of ct-DNA, and the fluorescence quenching by ct-DNA was static quenching type. Beside the multispectroscopic results, computational studies were done. Molecular docking results revealed that the TAH-DNAs complexes might be classified as druggable molecule in drug design. Additionally, DNA binding studies exhibited that TAH complexes have different interaction and orientation abilities to each DNA isomer. Combination of experimental and computational data showed that reported TAH is promising structure and deserves further applications.

The association between quality of life and complementary and alternative medicine use in patients with diabetes mellitus.

AIM: In the current study, we aimed to evaluate the relationship between life quality and use of complementary and alternative medicine (CAM) in patients with diabetes mellitus. METHODS: The Audit of Diabetes-Dependent Quality of Life (ADDQOL-19) scale was applied to 453 diabetic patients. Socio-demographic characteristics of the patients and their CAM usage were recorded. RESULTS: The rate of CAM use among diabetic patients was 46.1%. The most preferred practices were herbal medicine, including black cumin (26.6%), cinnamon (23.3%) and olive leaf (12.5%). 'Freedom to eat' (p = 0.002), 'drinking freedom' (p = 0.001) and 'physical health' (p = 0.001) were the most negatively affected items that may drive patients to use CAM. CONCLUSIONS: In this sampling, the use of CAM among patients with diabetes mellitus is high. The association between CAM usage and eating and drinking freedom and physical health should be studied in detail in further studies.

Why do patients with minor complaints choose emergency departments and does satisfaction with primary care services influence their decisions?

AimTo identify the reasons why patients with minor complaints choose emergency departments (EDs) as a first contact of care and whether dissatisfaction with primary care services influences their decisions. METHODS: In this study, a self-completed survey called EUROPEP was given to 535 outpatients who were admitted to the Bursa Yuksek Ihtisas Training and Research Hospital in Bursa and examined in the green zone in July 2015. Patients were asked about their complaints and why they preferred EDs as a first contact of care. RESULTS: EDs were the first contact of care in 87.8% of cases. In all, 9% of patients registered to family physicians who were working outside the city of Bursa. There was no relationship between patient satisfaction and the number of previous visits to EDs in last 12 months (P=0.09). The main reasons for admitting to the emergency services were feeling excessive pain (20.4%), perception of urgency (14.5%) and that the family doctor services were closed outside working hours (13.2%). The mean patient satisfaction with family practice offices was calculated to be 68.1%. CONCLUSIONS: The frequency of admission to EDs as a first contact of care was extremely high in the absence of a referral system. Patients who did not have family doctors in the settlement where they live put an extra burden on the EDs. Overall, patient satisfaction with their GPs did not influence the number of visits to EDs but accessibility remains a big challenge.

Study of Binding Properties Between Two New Ibuprofen and Naproxen Based Acyl Hydrazone Derivatives and Trypsin.

Two acyl hydrazone derivatives, AHI and AHN,made from ibuprofen and naproxen-derived hydrazides, were prepared and studied of binding properties with serine protease trypsin by UV-vis absorption and fluorescence quenching at pH 7.4. The results suggest that both hydrazones can interact strongly with trypsin and there are the formation of trypsin-hydrazone complexes. The Stern-Volmer constants, binding constants,binding sites and the corresponding thermodynamic parameters ΔH°, ΔS° and ΔG° were calculated at different temperatures.The effect of common metal ions on the constants was also discussed. The binding modes can be explained on the basis of hydrogen bonds and van der Waals forces. The binding distance(r) ~3 nm between the donor (trypsin) and acceptors (AHI and AHN) was obtained according to Förster's non-radiative energy transfer theory. Moreover, LOD and LOQ of hydrazones were calculated in the presence of trypsin.

Novel thiazolo[3,2-b]-1,2,4-triazoles derived from naproxen with analgesic/anti-inflammatory properties: Synthesis, biological evaluation and molecular modeling studies.

3-Substituted-1,2,4-triazole-5-thiones are versatile synthetic intermediates for the preparation of several biologically active N-bridged heterocyclic compounds, given that they have two reactive sites, thiocarbonyl and an amine nitrogen (N1/N4). For several years, our interest has focused on the synthesis of novel heterocyclic systems derived from 3-substituted-1,2,4-triazole-5-thiones having analgesic/anti-inflammatory activity. In this study, a series of novel thiazolo[3,2-b]-1,2,4-triazole-6(5H)-one derivatives bearing naproxen was synthesized and evaluated for their in vivo analgesic and anti-inflammatory properties in acute experimental pain and inflammation models. The compounds were also tested for their ulcerogenic potential. Our findings showed that all the newly synthesized derivatives attenuate nociception and inflammation compared with a control. All the synthesized compounds exhibited much lower ulcerogenic risk than the standard drugs indomethacin and naproxen. Some compounds with significant analgesic and/or anti-inflammatory activities as well as low ulcer scores were further evaluated for in vitro COX-1 and COX-2 inhibitory potential in a COX-catalyzed prostaglandin biosynthesis assay. Among the tested compounds, compound 1q showed the highest selectivity index (SI) of 4.87. The binding mode for some of the tested compounds to the cyclooxygenase (COX) enzymes was predicted using docking studies.

McbR/YncC: implications for the mechanism of ligand and DNA binding by a bacterial GntR transcriptional regulator involved in biofilm formation.

MqsR-controlled colanic acid and biofilm regulator (McbR, also known as YncC) is the protein product of a highly induced gene in early Escherichia coli biofilm development and has been regarded as an attractive target for blocking biofilm formation. This protein acts as a repressor for genes involved in exopolysaccharide production and an activator for genes involved in stress response. To better understand the role of McbR in governing the switch from exponential growth to the biofilm state, we determined the crystal structure of McbR to 2.1 Å. The structure reveals McbR to be a member of the FadR C-terminal domain (FCD) family of the GntR superfamily of transcriptional regulators (this family was named after the first identified member, GntR, a transcriptional repressor of the gluconate operon of Bacillus subtilis). Previous to this study, only six of the predicted 2800 members of this family had been structurally characterized. Here, we identify the residues that constitute the McbR effector and DNA binding sites. In addition, comparison of McbR with other members of the FCD domain family shows that this family of proteins adopts highly distinct oligomerization interfaces, which has implications for DNA binding and regulation.

BdcA, a protein important for Escherichia coli biofilm dispersal, is a short-chain dehydrogenase/reductase that binds specifically to NADPH.

The Escherichia coli protein BdcA (previously referred to as YjgI) plays a key role in the dispersal of cells from bacterial biofilms, and its constitutive activation provides an attractive therapeutic target for dismantling these communities. In order to investigate the function of BdcA at a molecular level, we integrated structural and functional studies. Our 2.05 Å structure of BdcA shows that it is a member of the NAD(P)(H)-dependent short-chain dehydrogenase/reductase (SDR) superfamily. Structural comparisons with other members of the SDR family suggested that BdcA binds NADP(H). This was demonstrated experimentally using thermal denaturation studies, which showed that BcdA binds specifically to NADPH. Subsequent ITC experiments further confirmed this result and reported a Kd of 25.9 µM. Thus, BdcA represents the newest member of the limited number of oxidoreductases shown to be involved in quorum sensing and biofilm dispersal.