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Background: Indole-based heterocyclic compounds play important roles in pharmaceutical chemistry due to their unexpected biological and pharmacological properties. Objective: Herein, we describe novel biological properties (antioxidant, antimicrobial and anti-cancer) of 3-bromo-1-ethyl-1H-indole (BEI) structure. Method: BEI was synthesized from 1-Methyl-2-phenylindole and N-bromosuccinimide and was characterized by using 1H and 13C NMR. Cytotoxicity was determined by MTT assay. Apoptosis analysis of BEI was determined by Arthur (TM) image-based Cytometer. Different methods were applied to assess the antioxidant activity of BEI. Molecular docking studies were conducted to determine the interactions of bonding between GST isozymes and BEI. Results: According to the antioxidant and antimicrobial activity assays, BEI compound showed reduced total antioxidant activity compared to the Trolox standard, whereas it showed moderate antimicrobial activity against Aspergillus niger and Phytophora eryhtrospora. Notably, the BEI compound demonstrated substantial selective cytotoxicity for the first time towards cancer cell lines, and there existed a significant decrease in the percentage of live cells treated with BEI, in comparison to the control ones. Interestingly, BEI exhibited a promising glutathione S-transferase isozymes inhibition. Conclusion: The results of this study suggest that BEI seems to be a promising molecule to be used in the design of new anti-cancer agents that provide superiority to present commercial anti-cancer drugs. Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [115Z020]; Van Yuzuncu Yil UniversityYuzuncu Yil University [FYL-2019-8301, FDP-2018-6862]; Pamukkale UniversityPamukkale University [PAU-BAP-2018-KRM-011]; Samsun Ondokuz Mayis UniversityOndokuz Mayis University [PYO.ZRT.1904.17.053] The authors thank The Scientific and Technological Research Council of Turkey (Project No: 115Z020), Van Yuzuncu Yil University (FYL-2019-8301 and FDP-2018-6862) Pamukkale University (PAU-BAP-2018-KRM-011) and Samsun Ondokuz Mayis University (PYO.ZRT.1904.17.053) for financial supporting of reactant and reagents. WOS:000631838700003 2-s2.0-85103033113 PubMed: 32951581

Background RNAs to be used in transcriptome analysis must be of high quality and pure in order to ensure maximum representation of the expressed genes. RNA isolation is difficult in hazelnut tissues containing large amounts of secondary metabolite, phenolic compounds and the cell wall structure. Commonly used protocols for RNA isolation are those that require a lot of labor and time and also do not allow sufficient RNA isolation when applied to tissues rich in phenolic compounds. This study was aimed to develop an efficient method for isolation of total RNAs from bud of hazelnut to be used in RNA sequencing. Materials and methods An optimized new method was successfully applied on three different hazelnuts genotypes (Çakıldak, Palaz, Tombul) and about 25 times higher amount of total RNAs per mg fresh tissues were obtained compared to classical CTAB method. Different methods have been tried for the isolation of RNA from hazelnut tissues and the determination of the quality of the obtained RNAs. Results The quality and quantity of isolalated total RNAs were determined by spectrophotometer, electrophoresis and PCR. This success has been caught without any compromise of purity since A260/A280 ratios ranged from 1.90 to 2.04 and A260/A230 ratios were >2.0 in all purified RNAs. Conclusion The total RNAs isolated with new protocol was found to be suitable for RNA sequencing and other molecular applications.

Thiophene derivatives are studied intensively due to their anticancer, antimicrobial, antioxidant and some other clinically important properties. In this study, the biological properties of a new thiophene derivative, so called BMPT, with a moderate drug score of 0.29 were tested. BMPT showed selective cytotoxicity for LnCap, HepG2 and Caco-2 cancer cell lines with EC50 values of 138.573 μM, 185.931 μM, and 108.657 μM, respectively, but not on the control cell line HEK293. The increased expressions were detected for caspase3, caspase8, caspase9 and Bax; but Bcl-2 expressions were decreased at cancer cell lines. BMPT decreased the total thiol content and total GST activities at HepG2 47 % and 40 %, respectively, and, molecular docking supported inhibitory models for GSTP1-1, GSTA1-1 and GSTM2-2 were mixed, uncompetitive and uncompetitive, respectively. BMPT also showed potent antibacterial activity against Staphylococcus aureus. Related with its selective inhibition on GST activities, BMPT is proposed to have significant apoptotic effect leaded by changes, especially, in caspase 3, Bcl-2 and Bax expressions.

Background: Marine actinomycetes are among indispensable sources of natural bioactive compounds with unique antimicrobial and anti-cancer activities. Objective: Herein, it was aimed to elucidate the bioactive potential of a marine-derived Streptomyces ovatisporus S4702T, isolated previously. Methods: Streptomyces ovatisporus S4702T was cultured in N-Z Amine broth, and extraction was carried out using different organic solvents. Bioassay-guided purification was followed by chemical characterization using NMR and LC-MS/MS. The compound was then evaluated for its antibacterial, antioxidant and cytotoxic activities. Results: Etyl acetate extracts gave the highest antibacterial activity, and chemical characterization of this extract indicated the formula as C15H29O5N3 and the corresponding possible molecular structure as 4H-chromen-4-one derivative. It was found highly potent against Bacillus subtilis ATCC 6633 (MIC: 0.25 μg ml-1) and Micrococcus luteus ATCC 9341 (MBC: 0.5 μg ml-1). It has no remarkable antioxidant activity, but a higher EC50 value and less cytotoxicity against normal cells. The EC50 values of this chromen derivative were found as 9.68 μg ml-1 for human colon carcinoma, 9.93 μg ml-1 for human prostate adenocarcinoma and 25.5 μg ml-1 for human embryonic kidney cells. Conclusion: Overall, the presented 4H-chromen-4-one derivative is a remarkable bioactive compound with potent antibacterial and cytotoxic activity. With its high bioactive potential, it is proposed as a good candidate in medicine.

Polyhydroxyalkanoates (PHAs) are leading “green” alternatives for the production of biodegradable plastics. They accumulate inside archaea and bacteria as the sources of carbon and energy under stress conditions. This study evaluates the biosynthesis of poly(3-hydroxybutyrate) (PHB), one of the major PHAs, in the extremely halophilic archaeon Haloarcula sp. TG1 by microscopic, spectroscopic, and thermal analyses. The PHB production by TG1 strain was optimized in terms of growth conditions and media. The optimum PHB content (34.6% of the biomass) was obtained in Mineral Salt Medium (MSM) cultures containing 5 M NaCl and 4% glucose, at pH 7.35, incubated for 72 h at 37 °C. Replacement of glucose with starch or glycerol lowered the PHB content in biomass. Alternatively, agricultural wastes (sugar beet pulp, corn cob, and hazelnut husk) were used as cheap carbon sources. The highest PHB content (45.6% of the biomass) was obtained using sugar beet pulp treated with recombinant endoglucanase (rCKT3eng), while PHB amount was 17.8% of the biomass with chemically hydrolyzed sugar beet pulp. In conclusion, PHB production by Haloarcula sp. TG1 was shown to be promising biotechnologically, using a low-cost fermentation medium at optimal culture conditions.

Indoles have very critical roles to design new biologically active molecules in medicinal chemistry. They display higher biological activities or create new biological properties when compared to the other heteroaromatic compounds. In the present study, 1-ethyl-2-phenyl-3-(thiophen-2-yl)-1H-indole (3), 8-ethyl-8H-benzo[a]thieno[3,2-c]carbazole (4), 1-ethyl-2-phenyl-3-(5-(phenylethynyl)thiophen-2-yl)-1H-indole (6) and 1-ethyl-3-(furan-2-yl)-2-phenyl-1H-indole (7) are prepared via Pd-catalyzed cross-coupling reactions and iodocyclization reactions. It was determined that compound 3 and 7 were also seemed to be better drug candidates at the end of in silico evaluation. Furthermore, compound 7 provided the best antibacterial and antifungal activity against the test indicator strains. It showed a potent antifungal effect on Aspergillus niger ATCC 16404 (MIC: 1.17 µg mL−1; MFC: 2.7 µg mL−1). In addition, while compounds 3, 6 and 7 showed significantly high molybdenum reducing activity compared to trolox, 7 exhibited almost the same antioxidant activity (EC50 = 7.1 µM) compared to the trolox standard (EC50 = 5.07 µM). After characterization, the cytotoxic activities of novel indoles were tested against different cancer cell lines and non-cancerous human cell line. Compound 3 and 7 had selective cytotoxic activity towards cancer cells. EC50 values of compound 3 were found to be 248.15 µM for LnCap, 139.81 µM for HepG2, and 164.72 µM for the Caco-2 cell line. Similarly, The EC50 value of 7 was found as 38.725 µM for LnCap, 70.02 µM for HepG2, and 86.98 µM for Caco-2, and 90.97 µM for Hek293 cell line. Moreover, it was revealed that these two compounds showed strong apoptotic properties towards these cancer cell lines as described by image cytometry and real time PCR. Consequently, these results improved that our molecules 3 and 7 could be new candidates as anticancer agents and apoptosis inducers. Indoles have very critical roles to design new biologically active molecules in medicinal chemistry. They display higher biological activities or create new biological properties when compared to the other heteroaromatic compounds. In the present study, 1-ethyl-2-phenyl-3-(thiophen-2-yl)-1H-indole (3), 8-ethyl-8H-benzo[a]thieno[3,2-c]carbazole (4), 1-ethyl-2-phenyl-3-(5-(phenylethynyl)thiophen-2-yl)-1H-indole (6) and 1-ethyl-3-(furan-2-yl)-2-phenyl-1H-indole (7) are prepared via Pd-catalyzed cross-coupling reactions and iodocyclization reactions. It was determined that compound 3 and 7 were also seemed to be better drug candidates at the end of in silico evaluation. Furthermore, compound 7 provided the best antibacterial and antifungal activity against the test indicator strains. It showed a potent antifungal effect on Aspergillus niger ATCC 16404 (MIC: 1.17 µg mL−1; MFC: 2.7 µg mL−1). In addition, while compounds 3, 6 and 7 showed significantly high molybdenum reducing activity compared to trolox, 7 exhibited almost the same antioxidant activity (EC50 = 7.1 µM) compared to the trolox standard (EC50 = 5.07 µM). After characterization, the cytotoxic activities of novel indoles were tested against different cancer cell lines and non-cancerous human cell line. Compound 3 and 7 had selective cytotoxic activity towards cancer cells. EC50 values of compound 3 were found to be 248.15 µM for LnCap, 139.81 µM for HepG2, and 164.72 µM for the Caco-2 cell line. Similarly, The EC50 value of 7 was found as 38.725 µM for LnCap, 70.02 µM for HepG2, and 86.98 µM for Caco-2, and 90.97 µM for Hek293 cell line. Moreover, it was revealed that these two compounds showed strong apoptotic properties towards these cancer cell lines as described by image cytometry and real time PCR. Consequently, these results improved that our molecules 3 and 7 could be new candidates as anticancer agents and apoptosis inducers.

Background: Streptomyces clavuligerus is prolific producer of cephamycin C, a medically important antibiotic. In our former study, cephamycin C titer was 2-fold improved by disrupting homoserine dehydrogenase (hom) gene of aspartate pahway in Streptomyces clavuligerus NRRL 3585. Objective: In this article, we aimed to provide a comprehensive understanding at the proteome level on potential complex metabolic changes as a consequence of hom disruption in Streptomyces clavuligerus AK39. Methods: A comparative proteomics study was carried out between the wild type and its hom disrupted AK39 strain by 2 Dimensional Electrophoresis-Matrix Assisted Laser Desorption and Ionization Time-Of-Flight Mass Spectrometry (2DE MALDI-TOF/MS) and Nanoscale Liquid Chromatography- Tandem Mass Spectrometry (nanoLC-MS/MS) analyses. Clusters of Orthologous Groups (COG) database was used to determine the functional categories of the proteins. The theoretical pI and Mw values of the proteins were calculated using Expasy pI/Mw tool. Results: “Hypothetical/Unknown” and “Secondary Metabolism” were the most prominent categories of the differentially expressed proteins. Upto 8.7-fold increased level of the positive regulator CcaR was a key finding since CcaR was shown to bind to cefF promoter thereby direcly controlling its expression. Consistently, CeaS2, the first enzyme of CA biosynthetic pathway, was 3.3- fold elevated. There were also many underrepresented proteins associated with the biosynthesis of several Non-Ribosomal Peptide Synthases (NRPSs), clavams, hybrid NRPS/Polyketide synthases (PKSs) and tunicamycin. The most conspicuously underrepresented protein of amino acid metabolism was 4-Hydroxyphenylpyruvate dioxygenase (HppD) acting in tyrosine catabolism. The levels of a Two Component System (TCS) response regulator containing a CheY-like receiver domain and an HTH DNA-binding domain as well as DNA-binding protein HU were elevated while a TetR-family transcriptional regulator was underexpressed. Conclusion: The results obtained herein will aid in finding out new targets for further improvement of cephamycin C production in Streptomyces clavuligerus.

Aims: In this study experiments were carried out to explore antioxidant, antimicrobial, cytotoxic properties of novel indole derivative 1-ethyl-2-phenyl-3-phenylethyl-3-thiophen-2-yl-1Hindole (EPI) together with its effect on glutathione S-transferases (GST) activities in human liver carcinoma (HepG2) cells. Background: Indoles probably represent one of the most important heterocyclic structures that have been attracting the interest of many scientists in drug discovery. Objective: The present study was carried out to explore antioxidant, antimicrobial, cytotoxic properties of novel indole derivative 1-ethyl-2-phenyl-3-phenylethyl-3-thiophen-2-yl-1H-indole (EPI) and its effect on glutathione S-transferases (GST) activities in human liver carcinoma (HepG2) cells. Materials and Methods: Pd-catalyst Sonogashira coupling reactions, MTT Assay, Antioxidant capacity test, Antimicrobial test, GST enzyme activity test Results: 1-ethyl-2-phenyl-3-(phenylethynyl)-1H-indole had antioxidant and antimicrobial properties. It displayed significant induction in glutathione S-transferases (GST) enzyme activity in human liver cancer cell lines (HepG2), but cytotoxic effect on all tested cancer cell lines could not be observed. Conclusion: All of these results showed that 1-ethyl-2-phenyl-3-(phenylethynyl)-1H-indole had antioxidant and antimicrobial properties without cytotoxic effect, which could make it a promising active component with further studies.. Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [115Z020]; Van Yuzuncu Yl University [FBA-2018-6901, FYL-2019-8301]; Pamukkale UniversityPamukkale University [PAU-BAP-2018-KRM-011]; Ondokuz Mays UniversityOndokuz Mayis University [PYO.ZRT.1904.17.053] The authors thank The Scientific and Technological Re-search Council of Turkey (Project No: 115Z020) , Van Yuzuncu Yl University (FBA-2018-6901 and FYL-2019-8301) and Pamukkale University (PAU-BAP-2018-KRM-011) and Ondokuz Mays University (PYO.ZRT.1904.17.053) for financial supporting of reactant and reagents. WOS:000677488500007 2-s2.0-85116036916

Marine actinomycetes are among indispensable sources of natural bioactive compounds with unique antimicrobial and anti-cancer activities.Herein, it was aimed to elucidate the bioactive potential of a marine-derived Streptomyces ovatisporus S4702T, isolated previously.Streptomyces ovatisporus S4702Etyl acetate extracts gave the highest antibacterial activity, and chemical characterization of this extract indicated the formula as C15H29O5N3 and the corresponding possible molecular structure as 4H-chromen-4-one derivative. It was found highly potent against Bacillus subtilis ATCC 6633 (MIC: 0.25 μg mlOverall, the presented 4H-chromen-4-one derivative is a remarkable bioactive compound with potent antibacterial and cytotoxic activity. With its high bioactive potential, it is proposed as a good candidate in medicine.

Streptomyces clavuligerus is prolific producer of cephamycin C, a medically important antibiotic. In our former study, cephamycin C titer was 2-fold improved by disrupting homoserine dehydrogenase (hom) gene of aspartate pahway in Streptomyces clavuligerus NRRL 3585.In this article, we aimed to provide a comprehensive understanding at the proteome level on potential complex metabolic changes as a consequence of hom disruption in Streptomyces clavuligerus AK39.A comparative proteomics study was carried out between the wild type and its hom disrupted AK39 strain by 2 Dimensional Electrophoresis-Matrix Assisted Laser Desorption and Ionization Time-Of-Flight Mass Spectrometry (2DE MALDI-TOF/MS) and Nanoscale Liquid Chromatography- Tandem Mass Spectrometry (nanoLC-MS/MS) analyses. Clusters of Orthologous Groups (COG) database was used to determine the functional categories of the proteins. The theoretical pI and Mw values of the proteins were calculated using Expasy pI/Mw tool."Hypothetical/Unknown" and "Secondary Metabolism" were the most prominent categories of the differentially expressed proteins. Upto 8.7-fold increased level of the positive regulator CcaR was a key finding since CcaR was shown to bind to cefF promoter thereby direcly controlling its expression. Consistently, CeaS2, the first enzyme of CA biosynthetic pathway, was 3.3- fold elevated. There were also many underrepresented proteins associated with the biosynthesis of several Non-Ribosomal Peptide Synthases (NRPSs), clavams, hybrid NRPS/Polyketide synthases (PKSs) and tunicamycin. The most conspicuously underrepresented protein of amino acid metabolism was 4-Hydroxyphenylpyruvate dioxygenase (HppD) acting in tyrosine catabolism. The levels of a Two Component System (TCS) response regulator containing a CheY-like receiver domain and an HTH DNA-binding domain as well as DNA-binding protein HU were elevated while a TetR-family transcriptional regulator was underexpressed.The results obtained herein will aid in finding out new targets for further improvement of cephamycin C production in Streptomyces clavuligerus.

KURT KIZILDOGAN, ASLIHAN/0000-0002-9323-0993 WOS: 000530831200012 PubMed: 31833007 lysA gene encoding meso-diaminopimelic acid (DAP) decarboxylase enzyme that catalyzes l-lysine biosynthesis in the aspartate pathway in Streptomyces clavuligerus was overexpressed, and its effects on cephamycin C (CephC), clavulanic acid (CA), and tunicamycin productions were investigated. Multicopy expression of lysA gene under the control of glpF promoter (glpFp) in S. clavuligerus pCOlysA led to higher expression levels ranging from 2- to 6-fold increase at both lysA gene and CephC biosynthetic gene cluster at T-36 and T-48 of TSBG fermentation. These results accorded well with CephC production. Thus, 1.86- and 3.14-fold higher volumetric as well as 1.26- and 1.71-fold increased specific CephC yields were recorded in S. clavuligerus pCOlysA in comparison with the wild-type and its control strain, respectively, at 48th h. Increasing the expression of lysA provided 4.3 times more tunicamycin yields in the recombinant strain. These findings suggested that lysA overexpression in S. clavuligerus made the strain more productive for CephC and tunicamycin. The results also supported the presence of complex interactions among antibiotic biosynthesis pathways in S. clavuligerus. Ondokuz Mayis UniversitesiOndokuz Mayis University [PYO.ZRT.1902-A.15.001]

WOS: 000535017800041 Heteroaromatic indoles play a leading role in the development of pharmaceutical, medical, chemical and agricultural fields due to their structural properties. In this study, it was first time that biological properties of (antioxidant, antimicrobial, cytotoxic and apoptotis-induced anticancer) 3-(5-bromothiophen-2-yl)-1-ethyl-2-phenyl-1H-indole 4 and 3-([2,2 '-bithiophen]-5-yl)-1-ethyl-2-phenyl-1H-indole 5 were described. According to the overall results, while 4 did not show any significant cytotoxic, antioxidant and antimicrobial activities, 5 showed high reducing activity and very strong antibacterial activity against Enterococcus faecalis. Furthermore, 5 showed dose-dependent cytotoxic effect in all tested cell lines. The EC50 values of the 5 were found to be 16 mu M for CaCo-2, 29 mu M for LnCaP, 14 mu M for MDA-MB231, 21 mu M for HepG2 and 87 mu M for HEK293 cells, respectively. 5 also caused induction of apoptosis and promising glutathione S-transferase (GST) enzyme inhibition in HepG2 cells. Consequently, 5 could be also considered as a promising medical agent in cancer treatment. Van Yuzuncu Yl University [FYL-2018-6798]; Pamukkale UniversityPamukkale University [PAU-BAP-2018-KRM-011]; YoK 100/2000; COST Action "Challenging organic syntheses inspired by nature - from natural products chemistry to drug discovery" [CM1407] The authors thank to Van Yuzuncu Yl University (FYL-2018-6798) and Pamukkale University (PAU-BAP-2018-KRM-011) for financial supporting of reactant and reagents. O. Ozok thanks to YoK 100/2000 for scholarships. The author (A. Kivrak) would like to acknowledge networking contribution by the COST Action CM1407 "Challenging organic syntheses inspired by nature - from natural products chemistry to drug discovery".

WOS: 000528267400120 PubMed: 31751744 Halophilic cellulases are indispensable enzymes of heavy industrial processes as resistant biocatalysts due to high level activity at extreme conditions. In this study, crude cellulase from an extreme halophilic Haloatrula sp. CKT3 was characterized. Then, recombinant expression of putative endo-1,4-beta-glucanase gene, of CKT3 strain, in E coli BL21(DE3) was performed with the aim of obtaining highly pure, active and robust industrial enzyme for such industrial aplications. The crude cellulase had optimal activity (16.9 U/mg) at 70 degrees C, pH 7.0 and 4 M Nacl exhibiting good thermostability, high pH and halotolerance. Indeed, it is very stable in water-insoluble organic solvents with log P-o/w >= 2.13 and highly resistant to SDS (10%). Recombinant CKT3eng has a molecular weight of 36.9 kDa and 99% aminoadd identity to endo-1,4-beta-D-glucanase from / Ialoarcula at gentinensis. Its 3D structure was predicted using Phyre2 and I-TASSER. rCKT3eng enzyme provided 31.6 U/mg activity at optimal 50 degrees C. pH 7.0 and 3 M NaCl. In addition to its quite similar stability values and resistance to organic solvents and SDS, rCKT3eng has superiority over crude enzyme with 1.87-fold higher specific activity. Therefore, rCKT3eng offers a promising enzyme for industrial use with its valuable activity and stability in extreme conditions. (C) 2019 Elsevier B.V. All rights reserved. Ondokuz Mayis University Research Fund (Samsun, Turkey)Ondokuz Mayis University [PYO.ZRT.1904.17.052] This study was supported by Ondokuz Mayis University Research Fund (Samsun, Turkey) with the project ID number of PYO.ZRT.1904.17.052. The authors acknowledge Omer KONUKSEVER for his technical assistance.

WOS: 000522352200030 A variety of highly substituted thieno[2,3-a]dibenzothiophenes and thieno[3,2-a]dibenzothiophenes are readily prepared via cascade electrophilic cyclization reaction. The reaction was tolerated a variety of compounds. In the present study, antimicrobial and antifungal activities were investigated for all synthesized molecules against A. niger ATCC 16404, C. albicans ATCC 10231, S. aureus ATCC 25923 and B. subtilis ATCC 6633, respectively. Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [115Z020] The authors thank to The Scientific and Technological Research Council of Turkey (Project No: 115Z020). The author(s) would like to acknowledge networking contribution by the COST Action CM1407 "Challenging organic syntheses inspired by nature from natural products chemistry to drug discovery".

Kavas, Musa/0000-0001-5903-2873; WOS: 000456979000002 PubMed: 30804627 The control of bud burst process depending on temperature is crucial factor in woody perennial plants to survive in unfavorable ecological conditions. Although it has important economic and agronomic values, little information is available on the molecular mechanism of the bud burst process in Corylus avellana. Here for the first time, we conducted a de novo transcriptome-based experiment using eco-dormant leaf bud tissues. Four transcriptome libraries were constructed from the leaf bud tissues and sequenced via Illumina platform. Transcriptome analysis revealed 86,394 unigenes with a mean length of 1189 nt and an N50 of 1916 nt. Among these unigenes, 63,854 (73.78%) of them were annotated by at least one database. De novo assembled transcripts were enriched in phenylpropanoid metabolism, phytohormone biosynthesis and signal transduction pathways. Analyses of phytohormone-associated genes revealed important changesduring bud burst, in response to gibberellic acid, auxin, and brassinosteroids. Approximately 2163 putative transcription factors were predicted, of which the largest number of unique transcripts belonged to the MYB transcription factor family. These results contribute to a better understanding of the regulation of bud burst genes in perennial plants. Research Fund of The Scientific and Technological Research Council of Turkey [114O800] This research was supported by a Research Fund of The Scientific and Technological Research Council of Turkey (114O800).

AYDEMIR, SELAHATTIN/0000-0002-0941-2779 WOS: 000462832500005 5-bromo-2-(prop-2-yn-1-yloxy)benzaldehyde (compound 3) and 3,5-di-tert-butyl-2-(prop-2-yn-1-yloxy)benzaldehyde (compound 5) were synthesized via nucleophilic substitution reactions. Compound 5 showed higher antioxidant capacity with respect to compound 3 in all the four different antioxidant activity methods used. Moreover, in phosphomolybdenum assay, compound 5, with 1.1 proportion value, showed almost the same total antioxidant capacity compared to universal trolox standard. Furthermore, Broth microdilution method and agar disc diffusion tests demonstrated that the same compound also exhibited good antibacterial activity towards the bacteria Bacillus subtilis. Finally, both of the benzaldehyde compounds showed high antifungal activity against Aspergillus niger. In this study, compound 5 (IC50: 54.3 mu g/ml) showed significant cytotoxic activity against breast adenocarcinoma cell line MCF-7 with respect to compound 3 (IC50: 173.4 mu g/ml). Van Yuzuncu Yil UniversityYuzuncu Yil University [BAP 2015-FBE-YL364, FBA-2016-5292] We thank to Van Yuzuncu Yil University (BAP 2015-FBE-YL364 and FBA-2016-5292) for the generous financial support.

Immunogenic potency of the recombinant Erp, HspR, LppX, MmaA4, and OmpA proteins from

OKAY, Sezer/0000-0003-0355-6672 WOS: 000356979700008 PubMed: 25917966 Pasteurella multocida is a Gram-negative bacterial pathogen causing economically important diseases in distinct animal species. Complete genome sequences of five P. multocida strains (Pm70, HB03, HN06, 3480, and 36950) isolated from poultry, swine or bovine, were retrieved from the GenBank database and compared with each other, for the first time. The missense mutations generating a dissimilar amino acid in the peptide chain, nonsense mutations, and insertion/deletions in the nucleotide sequence were identified due to the potential change in the protein function. A total of 500 putative mutant proteins were identified, and categorized into 10 groups including cellular compartments such as outer membrane, capsule and fimbria, and processes such as carbohydrate, energy, nucleic acid and amino acid metabolisms, transport, and drug resistance. The majority of the mutant proteins were associated with the outer compartments of the bacterial cell. Various mutations were also detected in the genes related with biosynthetic pathways. The highest and the lowest numbers of mutant proteins belonged to 36950 vs. HN06 and Pm70 vs. HB03 comparisons, respectively. The major impact on the diversification of P. multocida strains was observed to be conferred by the mutations related with pathogenicity. To exhibit the outcomes of the mutations in the peptide chains, three sample amino acid sequences belonging to AfuA, MetB, and D,D-heptose 1,7-bisphosphate phosphatase were aligned, and their phylogenetic relationships were shown. These comprehensive analyses improve the understanding of molecular pathogenicity and host specialization of P. multocida, and would have a contribution to the recombinant vaccine development against this pathogen. (C) 2015 Elsevier B.V. All rights reserved.

The control of bud burst process depending on temperature is crucial factor in woody perennial plants to survive in unfavorable ecological conditions. Although it has important economic and agronomic values, little information is available on the molecular mechanism of the bud burst process in Corylus avellana. Here for the first time, we conducted a de novo transcriptome-based experiment using eco-dormant leaf bud tissues. Four transcriptome libraries were constructed from the leaf bud tissues and sequenced via Illumina platform. Transcriptome analysis revealed 86,394 unigenes with a mean length of 1189 nt and an N50 of 1916 nt. Among these unigenes, 63,854 (73.78%) of them were annotated by at least one database. De novo assembled transcripts were enriched in phenylpropanoid metabolism, phytohormone biosynthesis and signal transduction pathways. Analyses of phytohormone-associated genes revealed important changes during bud burst, in response to gibberellic acid, auxin, and brassinosteroids. Approximately 2163 putative transcription factors were predicted, of which the largest number of unique transcripts belonged to the MYB transcription factor family. These results contribute to a better understanding of the regulation of bud burst genes in perennial plants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12298-018-0588-2) contains supplementary material, which is available to authorized users.

OKAY, Sezer/0000-0003-0355-6672 WOS: 000472623900006 PubMed: 30484328 Immunogenic potency of the recombinant Erp, HspR, LppX, MmaA4, and OmpA proteins from Mycobacterium tuberculosis (MTB), formulated with Montanide ISA 720 VG adjuvant, was evaluated in BALB/cmice for the first time in this study. The five vaccine formulations, adjuvant, and BCG vaccine were subcutaneously injected into mice, and the sera were collected at days 0, 15, 30, 41, and 66. The humoral and cellular immune responses against vaccine formulations were determined by measuring serum IgG and serum interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) levels, respectively. All formulations significantly increased IgG levels post-vaccination. The highest increase in IFN-gamma level was provided by MmaA4 formulation. The Erp, HspR, and LppX formulations were as effective as BCG in enhancement of IFN-gamma level. The most efficient vaccine boosting the IL-12 level was HspR formulation, especially at day 66. Erp formulation also increased the IL-12 level more than BCG at days 15 and 30. The IL-12 level boosted by MmaA4 formulation was found to be similar to that by BCG. OmpA formulation was inefficient in enhancement of cellular immune responses. This study showed that MmaA4, HspR, and Erp proteins from MTB are successful in eliciting both humoral and cellular immune responses in mice. Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [214S359] This study is funded by The Scientific and Technological Research Council of Turkey (TUBITAK) with the project number of 214S359. The authors would like to thank Dr. Erkan Ozcengiz for his valuable suggestions.

WOS: 000441422400002 Benzothiophene derivatives were synthesized regioselectively using coupling reactions and electrophilic cyclization reactions. Antimicrobial properties of isolated compounds were tested against indicator microorganisms such as C. albicans ATCC 10231, B. subtilis ATCC 6633, E. coli ATCC 25922 and S. aureus ATCC 25923. 3-(4-aminobenzoethynyl)-2-(thiophen-2-yl) benzo[b]thiophene (12E), 3-ethynyl-2-(thiophen-2-yl) benzo[b]thiophene (12L) and 3-(2-aminobenzoethynyl)-2-(thiophen-2-yl) benzo[b]thiophene (12J) displayed high antibacterial activity against S. aureus. Further, 3-iodo-2-(thiophen-2-yl) benzo[b]thiophene (10) and 3-(trimethylsilylethynyl)-2-(thiophen-2-yl) benzo[b] thiophene (12K) were found to have potentials to be used as antifungal agents against current fungal diseases. Novel 3-(1H-indole-2-yl)-2-(thiophen-2-yl) benzo[b] thiophene (16) and 3-(4-aminobenzoethynyl)-2-(thiophen-2-yl) benzo[b] thiophene (12E) also showed quite high antioxidant capacities with TEAC values of 2.5 and 1.1, respectively; which surpassed the antioxidant capacity of an universally accepted reference of trolox. Benzothiophene derivatives were synthesized regioselectively using coupling reactions and electrophilic cyclization reactions. Antimicrobial properties of the compounds were tested against four indicator microorganisms, and a few displayed high antibacterial activity against S. aureus. 3-(1H-indole-2-yl)-2-(thiophen-2-yl)benzo[b]thiophene (16) and 3-(4-aminobenzoethynyl)-2-(thiophen-2-yl)benzo[b]thiophene (12E) showed high antioxidant capacities which are better than the reference of trolox. Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [115Z020]; Van Yuzuncu Yil UniversityYuzuncu Yil University [FBA-2017-6007]; University of Duhok The authors thank to The Scientific and Technological Research Council of Turkey (Project No: 115Z020) for financial supporting of silica gels, column chromatographic solvents, all other reactants and reagents. Authors, also, thank Van Yuzuncu Yil University (Project No: FBA-2017-6007) for financial supporting of glassware and salts and University of Duhok for a scholarship to Muheb A. S. Algso.

OKAY, Sezer/0000-0003-0355-6672 WOS: 000405121500009 Objective: Isolation of halophilic microorganisms from Cankiri salt mine and Lake Tuz in Turkey to explore versatile protease producers for industry and characterization of protease enzyme from the best protease producer among the isolated strains. Methods: Extreme halophiles were isolated from salt samples of Cankiri salt mine and Lake Tuz. Their protease activities were determined. The isolate with the highest protease activity was characterized. Its protease activity was evaluated in different NaCl concentrations, temperature and pH ranges, and in the presence of different inhibitors and metals. Thermostability and pH stability were also determined. Results: The highest protease producer strain was identified as Haloarcula sp. on the basis of 16S rRNA analysis. The isolate namely, Haloarcula sp. TG1, was found to be 99% identical to Haloarcula salaria strain HST01-2R. The TG1 protease was found to possess very high activity and stability over a broad pH and temperature ranges. Its maximum activity was recorded at pH: 4.0, 50 degrees C and 4 M NaCl. Among inhibitors tested, dimethyl sulfoxide ( DMSO) and ethanol caused the highest decrease (ca. 25%) in its activity. Conclusion: Due to the high activity and stability over a wide range of extreme conditions, Haloarcula sp. TG1 protease reported here is a promising candidate in biotechnology. Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [KBAG-214Z171]; 2210-C TUBITAK National Scholarship Programme for Priority Areas for MSc Students We gratefully acknowledge The Scientific and Technological Research Council of Turkey (TUBITAK) grant number KBAG-214Z171 (Principal Investigator Dr. Sezer OKAY), for supporting this study. Busra ABANOZ was supported by 2210-C TUBITAK National Scholarship Programme for Priority Areas for MSc Students.

OKAY, Sezer/0000-0003-0355-6672 WOS: 000393016200007 PubMed: 27919704 Extremely halophilic archaea survive in the hypersaline environments such as salt lakes or salt mines. Therefore, these microorganisms are good sources to investigate the molecular mechanisms underlying the tolerance to high salt concentrations. In this study, a global transcriptome analysis was conducted in an extremely halophilic archaeon, Halolamina sp. YKT1, isolated from a salt mine in Turkey. A comparative RNA-seq analysis was performed using YKT1 isolate grown either at 2.7 M NaCl or 5.5 M NaCl concentrations. A total of 2149 genes were predicted to be up-regulated and 1638 genes were down-regulated in the presence of 5.5 M NaCl. The salt tolerance of Halolamina sp. YKT1 involves the up-regulation of genes related with membrane transporters, CRISPR-Cas systems, osmoprotectant solutes, oxidative stress proteins, and iron metabolism. On the other hand, the genes encoding the proteins involved in DNA replication, transcription, translation, mismatch and nucleotide excision repair were down-regulated. The RNA-seq data were verified for seven up-regulated genes as well as six down-regulated genes via qRT-PCR analysis. This comprehensive transcriptome analysis showed that the halophilic archaeon canalizes its energy towards keeping the intracellular osmotic balance minimizing the production of nucleic acids and peptides. (C) 2016 Elsevier B.V. All rights reserved. TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [KBAG-214Z171, 2210-C] This study was supported by TUBITAK project number KBAG-214Z171, and as the thesis of Busra Abanoz by TUBITAK 2210-C Scholarship Program for Domestic MSc Studies on Priority Subjects.

Bu calismada, karbon kaynagi olarak farkli bitkisel yaglarin Streptomyces clavuligerus ATCC27064 susunda klavulanik asit uretimi uzerine etkisinin belirlenmesi amaclanmistir. Fermentasyon besiyerinde zeytinyagi, misirozu yagi, aycicegi yagi ve findik yagi varliginda 168 saat suresince 28 o C ve 220 rpm’de inkube edilen kulturlerin kontrole kiyasla daha iyi ureme profili gosterdigi bulunmustur. Agar plak difuzyon deney sonuclarina gore, aycicegi ve zeytinyaginda S. clavuligerus ATCC27064 tarafindan uretilen klavulanik asit miktari kontroldekinden daha dusuk tespit edilmistir. En yuksek klavulanik asit uretimi (1526.4 mg L -1 ) inkubasyonun 120. saatinde (T 120 ) ve ile findik yaginin kullanilmasi ile elde edilmistir. Sonuclar, findik yaginin test edilen diger bitkisel yaglarla karsilastirildiginda S. clavuligerus ATCC27064'taki klavulanik asit uretimi uzerinde belirgin bir ustunluk sagladigini gostermektedir.