Aminopyrazole-substituted metallophthalocyanines: Preparation, aggregation behavior, and investigation of metabolic enzymes inhibition properties.

The synthesis, characterization, aggregation behavior, theoretical studies, and investigation of antimicrobial, antidiabetic, and anticholinergic properties of 4-(2-(5-amino-4-(4-bromophenyl)-3-methyl-1H-pyrazol-1-yl)ethoxy)phthalonitrile (2) and its soluble aminopyrazole-substituted peripheral metallo (Mn, Co, and Ni)-phthalocyanine complexes (3-5) are reported for the first time. The synthesized compounds and phthalocyanine complexes were characterized spectroscopically. The new phthalonitrile derivative (2) and its peripheral metallophthalocyanine complexes (3-5) were found to be effective inhibitors of α-glycosidase, acetylcholinesterase (AChE), human carbonic anhydrase I and II isoforms (hCA I and II), and butyrylcholinesterase (BChE) with Ki values in the range of 1.55 ± 0.47 to 10.85 ± 3.43 nM for α-glycosidase, 8.44 ± 0.32 to 21.31 ± 7.91 nM for hCA I, 11.73 ± 2.82 to 31.03 ± 4.81 nM for hCA II, 101.62 ± 26.58 to 326.54 ± 89.67 nM for AChE, and 68.68 ± 11.15 to 109.53 ± 19.55 nM for BChE. This is the first study of peripherally substituted phthalocyanines containing an aminopyrazole group as potential carbonic anhydrase enzyme inhibitor. Also, the antimicrobial activities of the synthesized compounds were evaluated against six microorganisms (four bacteria and two Candida species) using the broth microdilution method. The gram-positive bacteria were detected to be more sensitive than gram-negative bacteria and yeasts in the synthesized compounds.

The Effects of different nitrogen doses on antioxidant and antimicrobial activity of Stevia (Stevia rebaudiana Bert.).

In this study, the efficiency of the different nitrogen doses (0, 5, 10, 15 and 20 kg ha-1) on biological activity levels (antioxidant and antimicrobial activity) of Stevia rebaudiana Bert. was investigated. In addition, methanol extracts were obtained by maceration method from different doses of fertilizer applied stevia. The components in methanol extracts of plants were determined by gas chromatography-mass spectrometry (GC-MS) method. Antimicrobial activities of stevia extracts were investigated by microdilution method. The antioxidant activity evaluated by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric thiocyanate (FTC), thiobarbituric acid (TBA), reducing power, total phenol content (TPC), and total flavonoid content (TFC) methods. According to the results, the fertilizer doses effects on antimicrobial activity of stevia were not made much difference. But in antioxidant activity, there were some variations in the activity-dependent on fertilizer amount.

Determination of inhibitory activities of enzymes, related to Alzheimer's disease and diabetes mellitus of plane tree (Platanus orientalis L.) extracts and their antioxidant, antimicrobial and anticancer activities.

Plane tree (Platanus orientalis L.) leaves have been employed for centuries in various countries due to their pharmacological value. Therefore, determination of the biological activity of the leaves is of interest. The aim of the study was to evaluate the inhibitory effects against Alzheimer's disease-related enzymes Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE), diabetes mellitus related enzymes α-glucosidase and α-amylase. The antioxidant, anticancer, and antimicrobial activities of the leaves were also studied. According to the results, both water and methanol extracts of P. orientalis demonstrated more α-glucosidase and α-amylase inhibition activity than the antidiabetic drug-acarbose at the same concentration level. In addition, extracts showed good inhibition activity against AChE and BuChE. Significant results were obtained regarding antioxidant, anticancer, and antimicrobial activities. These results are very promising especially for the improvement of pharmaceutical formulations to treat various diseases such as age-related diseases, cancer, diabetes etc. and it is necessary to conduct further experiments.

Investigation of anti-proliferative and antioxidative effects of some bis (α-amino) phosphinic acid derivatives.

Aminophosphinic acids which are organophosphorus compounds widely investigated for potential production of antibacterial, antitumor and antiviral materials. In vitro antioxidant, cytotoxic and antimicrobial activities of synthesized novel compounds of 8 different bis(ß-amino alkyl)phosphinic acids (4a-h) were investigated on MCF-7 breast adenocarcinoma cell and human umbilical vein endothelial cell (HUVEC) cultures. Malondialdehyde (MDA) levels were evaluated as an indication of lipid peroxidation in cell cultures for antioxidant capacities. In vitro antioxidant activities in cell cultures were determined by evaluating totals of antioxidant, oxidant, thiol levels and activities of paraoxanase, aryl esterase. It was found that 4c compound reduced MDA level significantly while 4a and 4g compounds increased MDA levels significantly compared to control. 4c compound was found most effective in reducing MDA levels by neutralizing reactive oxygen species to prevent cell damage while compounds 4c, 4f and 4h were found presenting adequate activity with other antioxidants. In vitro anti-proliferation was evaluated on MCF-7 and HUVEC cells using XTT to investigate anti-cancer potentials as therapeutics. Compounds 4c, 4e and 4f were exhibited better compared to others. Most compounds were found cytotoxic to both MCF-7 and HUVECs. Antimicrobial and antifungal activities were investigated by disc diffusion and compared to MICs of Gentamycin and Nystatin.

The pharmacological properties of Gypsophila eriocalyx: The endemic medicinal plant of northern central Turkey.

The aim of this study is to evaluate and compare the biological properties of different extracts (methanol, ethanol, and water) obtained from Gypsophila eriocalyx (G. eriocalyx), a medicinal plant traditionally used in Turkey. The components of different extracts were defined using the GC-MS method. The effects of G. eriocalyx extracts on cell proliferation, apoptosis, and cell cycle arrest in MDA-MB-231 breast cancer as well as in vitro antioxidant, enzyme inhibition, and antimicrobial activities were investigated. In accordance with the results obtained, although ethanol and methanol extracts of G. eriocalyx show higher antioxidant activity than G. eriocalyx water extract, enzyme inhibition activities of the extracts were not found to be significant compared to the reference drug. The methanol and ethanol extract of G. eriocalyx exhibited moderate antimicrobial activity against Staphylococcus aureus and methanol extract showed significant antimicrobial activity against Bacillus cereus. In addition, both extracts significantly inhibited cell viability in a dose-dependent manner in breast cancer cells. The cell growth inhibition by methanol and ethanol extracts induced S phase cell-cycle arrest and apoptosis in MDA-MB-231 cells. Lastly, in order to compare the activities of the chemicals found in Gypsophila eriocalyx plant extract, their activities against various proteins that are breast cancer protein (PDB ID:1A52 and 1JNX), antioxidant protein (PDB ID: 1HD2), AChE enzyme protein (PDB ID: 4M0E), BChE enzyme protein (PDB ID: 5NN0), and Escherichia coli protein (PDB ID: 4PRV)were compared. Then, ADME/T analysis calculations were made to examine the effects of molecules with high activity on human metabolism. Eventually, G. eriocalyx is thought to be a potent therapeutic herb that can be considered as an alternative and functional therapy for the management of diseases of a progressive nature related to oxidative damage such as infection, diabetes, cancer, and Alzheimer's disease.

In vitro susceptibility of isolates of Francisella tularensis from Turkey.

BACKGROUND: Tularemia is an infection caused by Francisella tularensis, which has a wide distribution in the northern hemisphere and diverse clinical manifestations. For decades, the drug of choice for the treatment of tularemia has been streptomycin, with tetracycline and chloramphenicol being used as alternatives. The purpose of the present study was to determine the in vitro antimicrobial susceptibility of a large panel of geographically diverse F. tularensis isolates from Turkey against traditional and newer antimicrobial agents. METHODS: The antibiotic susceptibilities of 250 F. tularensis strains were examined using the Epsilometer test for 9 antimicrobial agents. Each isolate was identified by conventional and molecular techniques. RESULTS: All the strains were confirmed biochemically and using a combination of species- and subspecies-specific polymerase chain reaction (PCR) assays to be F. tularensis subsp. holarctica. One isolate was assigned to F. tularensis subsp. holarctica biovar japonica based on erythromycin susceptibility, an ability to ferment glycerol, and the nucleotide sequence of the region of difference 1 (RD1). All strains were susceptible to aminoglycosides (streptomycin and gentamicin), tetracyclines (tetracycline and doxycycline), chloramphenicol, 2 fluoroquinolones (ciprofloxacin and levofloxacin), and rifampicin. In addition, all isolates except 1 had a minimal inhibitory concentration (MIC) for erythromycin of > 256 µg/ml. CONCLUSIONS: Since the fluoroquinolones showed the lowest MIC values and have advantages such as excellent bioavailability and activity, availability of oral formulations, and lower toxicities, they represent candidate therapeutic options in the first-line treatment of tularemia. To the best of our knowledge, this is the first report of the presence of F. tularensis subsp. holarctica biovar japonica outside Japan.

[Seroprevalence of tick-borne encephalitis virus (TBEV) among the residents of rural areas in Sinop, central Black-Sea region, Turkey]. / Sinop'ta kirsal kesimde yasayan kisilerde kene kaynakli ensefalit virusu (TBEV) seroprevalansi

Tick-borne encephalitis (TBE), caused by tick-borne encephalitis virus (TBEV) is one of the serious neurological infections seen especially in the Asian and North European countries. The principal vectors of TBEV are hard ticks belonging to Ixodes genus. The major vector of European TBEV subtype is I.ricinus and the major vector of Far-Eastern and Siberian subtypes is I.persulcatus. I.ricinus exists in many climatic regions of Turkey, especially in the coastal areas. The aim of this study was to investigate the TBEV seroprevalence among the residents of rural areas in Sinop (a province located at the coast of Central Black-Sea region of Turkey). A total of 273 blood samples have been collected from the subjects (age range: 11-83 years) inhabiting in 12 villages of the central district of Sinop, during the months of May and June in 2006 and 2007. The presence of TBEV IgG antibodies in serum samples were searched by a commercial indirect fluorescent antibody kit (Euroimmun, Deutschland). TBEV IgG positivity was detected in 2.9% (8/273) of the subjects at a screening titer (1/10) and 7 (2.6%) of them also yielded positive results at further dilutions (1/100). The rates of TBEV seropositivity were not found statistically significant (p > 0.05), with respect to gender (141 of the subjects were male), age (142 of the subjects were between 21-50 years old), occupation (17 foresters, 57 were shepherds, 199 were farmers/stockbreeders) and history of tick bite (169 of the subjects had been bitten by ticks). Presence of IgG antibodies against Borrelia burgdorferi, another agent which is transmitted by the same vector, were also investigated in TBEV seropositive 8 subjects by a commercial ELISA kit (Zeus Scientific, The Netherlands). Four of these subjects yielded B.burgdorferi IgG positivity, so the TBEV - B.burgdorferi coinfection rate was estimated as 1.5% (4/273). However, since the results obtained by the tests used in this study (TBEV IgG IFA and B.burgdorferi IgG ELISA) have not been confirmed by additional confirmational tests, these subjects were referred as "probable cases". In recent years the detection rates of vector-borne viral infections is in an increment trend in Turkey due to the developments in diagnostic tests and awareness for emerging infections. In conclusion since Sinop, which is placed in the northernmost point of Turkey, is located close to TBEV endemic areas, the presence of TBEV in Sinop and the Black Sea region should always be considered.

The Prevalence of Tick-Borne Pathogens in Ticks Collected from the Northernmost Province (Sinop) of Turkey.

Ixodes ricinus is a potential vector for some of the tick-borne microorganisms that can cause significant diseases in animals and humans. This study aims to determine the prevalence of Anaplasma, Rickettsia, Bartonella, and Francisella species in host-seeking ticks collected from the forest areas in the Sinop region located in the northernmost part of Turkey. Between May and July 2017, a total of 135 tick pools formed from 2571 of the 2734 ticks collected out of the vegetation. Samples of each pool were homogenized and analyzed by PCR. Infection prevalence was statistically analyzed in view of the maximum likelihood estimation (MLE) with a 95% confidence interval (CI). DNA of the infectious agents was determined only in the adult and nymph pools of I. ricinus. MLE values of Anaplasma spp. and Bartonella spp. in 58 pools formed from 517 of I. ricinus adults were 1.20% (95% CI: 0.50-2.49) and 0.80% (95% CI: 0.26-1.91), respectively. In 42 pools generated from 1222 of I. ricinus nymph, MLE values of infection prevalence for Anaplasma spp. and Bartonella spp. were calculated to be 0.17% (95% CI: 0.03-0.54) and 0.34% (95% CI: 0.11-0.82) in respective order. MLE values for Rickettsia spp. were 7.55% (95% CI: 5.21-10.69) and 0.52% (95% CI: 0.22-1.083) for the adult and nymph I. ricinus, respectively. The DNA of Francisella tularensis was not detected in any tick pool. The outcomes of this research are the first molecular evidence of Bartonella spp. and Bartonella henselae in questing I. ricinus in Turkey. The results also suggested that I. ricinus plays considerable roles in enzootic transmission cycles of Anaplasma phagocytophilum, B. henselae, and Rickettsia monacensis in the northernmost region of Turkey.

Determination of biological activity of Tragopogon porrifolius and Polygonum cognatum consumed intensively by people in Sivas.

OBJECTIVE: This study was aimed to investigate the in vitro antioxidant, antimicrobial, cytotoxicity, and enzyme inhibition activities of Tragopogon porrifolius and Polygonum cognatum which are naturally grown and consumed intensively by people in Sivas, Turkey. METHODS: Plant materials were extracted with aqueous ethanol by maceration method. The components of the extracts were determined using the Gas Chromatography Mass Spectrometry. Antimicrobial, cytotoxic and enzyme inhibition activities of the extracts were investigated by micro dilution, XTT assay and 96-micro-well plate methods, respectively. The antioxidant activity evaluated using the DPPH radical scavenging, thiobarbituric acid and reducing power methods. The total phenol and total flavonoid content was also examined. RESULTS: GC-MS analysis revealed the presence of 31 compounds inP. cognatum extract and 29 compounds in T. porrifolius extract. According to the results, T. porrifolius extract showed high level of antioxidant activity in comparison to P. Cognatum extract. T. porrifolius exhibited higher α-glucosidase inhibitory activity, and both extract showed strong α-amylase inhibition activity compared to reference drug acarbose. T. porrifolius and P. cognatum ethanolic extracts exhibited antimicrobial activity in the concentration range of 0.039-2.5 mg/ml. Both extracts also exhibited significant anticancer effect on MDA-MB-231 breast cancer cells. The IC50 values of T. porrifolius and P. cognatum extracts in MDA-MB-231 cells were determined as 0.0625 mg/mL and 0.053 mg/mL, respectively. CONCLUSION: Our findings demonstrated that T. porrifolius and P. cognatum ethanolic extracts have promising effect on antioxidant, antimicrobial and cytotoxic activity as well as enzyme inhibition activity, and hence further studies required to identify specific compounds responsible for these activities.

In Vitro Evaluation of the Chemical Composition and Various Biological Activities of Ficus carica Leaf Extracts.

OBJECTIVES: The present study aimed to investigate the inhibitory activities of enzymes related to diabetes mellitus and Alzheimer's disease of the methanol and water extracts of Ficus carica leaf extracts. The bioactive compounds and anticancer, antioxidant, and antimicrobial effects of the extracts were also investigated. MATERIALS AND METHODS: The bioactive compounds in the extracts were determined by gas chromatography-mass spectrometry. The antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6 sulphonic acid) (ABTS) radical scavenging, total phenol and flavonoid content, ferric reducing power, and iron chelating method. The anticancer, anticholinesterase, and antimicrobial effects were investigated using the XTT assay, Ellman method, and microdilution, respectively. RESULTS: Our results showed that between the water and methanol extracts there was a difference in terms of chemical composition. The antioxidant results suggested that both extracts have strong antioxidant activity. Similarly, both extracts showed strong α-glucosidase and α-amylase inhibition activity, while the water extract had higher inhibition activity than the methanol extract against acetylcholinesterase and butyrylcholinesterase. The methanol extract of F. carica exhibited significant anticancer activity on MDA-MB-231 cells and showed moderate antimicrobial activities against Escherichia coli and Staphylococcus aureus. CONCLUSION: Our results suggest that F. carica leaves could be a valuable source for developing a promising therapeutic agent in cancer, diabetes, and Alzheimer's disease.

[Distribution of intestinal parasites in patients presenting at the environmental-food and medicine analysis laboratory of Sivas municipality during the years 1993-2006]. / Sivas Belediyesi Cevre-Gida ve Tibbi Tahlil Laboratuvarina 1993-2006 Yillarinda Basvuran Hastalarda Bagirsak Parazit Dagilimlarinin Incelenmesi.

The purpose of the present study was to investigate retrospectively the distribution and prevalence of intestinal parasites in patients who presented at the environmental-food and medicine analysis laboratory of the Sivas municipality, Sivas, from January 1993-December 2006. A total of 732 stool specimens were examined for intestinal parasites using native-Lugol and formol ethyl ether methods. Also, 186 cellophane tape preparations were examined directly. Out of a total of 918 total specimens, intestinal parasites were found in 85 (9.3%) females and 178 (19.4%) males. Parasites were found in 188 (25.7%) of the stool specimens, coming from 54 (7.4%) females and 134 (18.3%) males. Of the 75 positive cellophane tape specimens, 31 (16.7%) were females and 44 (23.7%), male. The prevalence of intestinal parasites was evaluated according to years, sex and ages in which cases were seen. The distribution of intestinal parasites detected in stool specimens was as follows: 101 (13.8%) Entamoeba coli, 27 (3.7%) Entamoeba histolytica/dispar, 91 (12.4%) Giardia intestinalis, 30 (4.1%) Taenia saginata, 13 (1.8%) Hymenolepis nana, 7 (1%) Ascaris lumbricoides, 2 (0.3%) Trichuris trichiura and 1 (0.1%) Dicrocoelium dentriticum. Parasites detected in cellophane tape specimens included 64 (34.4%) Enterobius vermicularis and 11 (5.9%) Taenia saginata.

[The investigation of intestinal parasites in two primary schools in different social-economic districts of the city of Yozgat, Turkey]. / Yozgat Il Merkezinde Farkli Sosyo-Ekonomik Bölgelerdeki Iki Ilkögretim Okulunda Bagirsak Parazitlerinin Arastirilmasi.

The aim of this study was to determine the incidence of intestinal parasites among children in two primary schools in different social-economic districts in the central region of Yozgat and to educate the children about parasitic diseases. During the study, cellophane tape preparations and stool samples that had been prepared using direct mounting methods were examined. In addition the students were informed about intestinal parasites. Parasitic infection was observed in 128 (34.9%) out of 367 students and the highest rate of 16.1% was that of Entamoeba coli. The rate of Giardia intestinalis, Enterobius vermicularis, Hymenolepis nana, Entamoeba histolytica/dispar, Taenia saginata, Ascaris lumbricoides and Trichuris trichiura were found to be 15.5%, 8.4%, 2.2%, 1.6%, 1.6%, 1.6% and 0.5%, respectively. In cases with parasitosis, one species of parasite was found in 68.0%, 2 species in 27.3% and 3 species in 4.7%. Thus, intestinal parasites are important among primary school children in Yozgat and it seems that there is a relationship between socio-economic conditions and the rate of intestinal parasites.