Cloning, Purification and Characterization of Acetyl Xylane Esterase from Anoxybacillus flavithermus DSM 2641(T) with Activity on Low Molecular-Weight Acetates

Eminoglu, Aysenur/0000-0003-1693-6332; SANDALLI, Cemal/0000-0002-1298-3687WOS: 000359809700001PubMed: 26126589Family 4 carbohydrate esterases (CE-4) have deacetylate different forms of acetylated poly/oligosaccharides in nature. This family is recognized with a specific polysaccharide deacetylase domain assigned as NodB homology domain in their secondary structure. Most family 4 carbohydrate esterases have been structurally and biochemically characterized. However, this is the first study about the enzymological function of pdaB-like CE4s from thermophilic bacterium Anoxybacillus flavithermus DSM 2641(T). A. flavithermus WK1 genome harbors five putative CE4 family genes. One of them is 762 bp long and encodes a protein of 253 amino acids in length and it was used as reference sequence in this study. It was described as acetyl xylane esterase (AXE) in genome project and this AfAXE gene was amplified without signal sequence and cloned. the recombinant protein was expressed in E. coli BL21 (DE3), purified by nickel affinity chromatography and its purity was visualized on SDS-PAGE. the activity of the recombinant enzyme was shown by zymogram analysis with alpha-naphtyl acetate as a substrate. the enzyme was characterized spectrophotometrically using chromogenic p-nitrophenyl acetate. Optimum temperature and pH were determined as 50 A degrees C and 7.5, respectively. Km and Vmax were determined as 0.43 mM and 3333.33 U/mg, respectively under optimum conditions. To our knowledge this is the first enzymological characterization of a pdaB-like family 4 carbohydrate esterase from the members of Anoxybacillus genus.Recep Tayyip Erdogan University Research FundRecep Tayyip Erdogan University [BAP- 2011.102.03.3, BAP- 2012.102.03.4]This work was supported by Recep Tayyip Erdogan University Research Fund Grants BAP- 2011.102.03.3 and BAP- 2012.102.03.4

Synthesis of some novel heterocylic compounds derived from 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide and investigation of their lipase and alpha-glucosidase inhibition

WOS: 000369915500019PubMed: 25640970In the present study, 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide (1) was used as starting compound for the synthesis of 2-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetyl}-4-thiosemicarbazides (2a-c) and 5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-1,3,4-oxadiazole-2-thione (5). the cyclization of compounds 2a-c in the presence of NaOH resulted in the formation of 5-{[3-( 4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones(3a-c). Aminomethylation of compounds 3a-c and 5 with formaldehyde and N-methyl/phenylpiperazine furnished Mannich bases (4a-f and 6a-b). the newly synthesized compounds were well-characterized by IR, H-1 NMR, C-13 NMR, elemental analysis and mass spectral studies. They were also screened for their lipase and alpha-glucosidase inhibition. Among the tested compound 2c (IC50 = 2.50 +/- 0.50 mu M) showed the best anti-lipase activity and compounds 2c (IC50 = 3.41 +/- 0.16 mu M) and 6a (IC50 = 4.36 +/- 0.10 mu M) showed the best anti-alpha- glucosidase activity.Karadeniz Technical University, BAP, TurkeyKaradeniz Technical University [10020]The support provided by Karadeniz Technical University, BAP, Turkey (Project No. 10020) is gratefully acknowledged

Design, Synthesis, and Biological Evaluation of Coumarin-Triazole Hybrid Molecules as Potential Antitumor and Pancreatic Lipase Agents

WOS: 000406714000001PubMed: 28543820The design, synthesis, and investigation of antitumor and anti-lipase activities of some coumarin-triazole hybrid molecules are reported. the synthesis of these hybrid molecules was performed under microwave irradiation and conventional heating procedures. the newly synthesized hybrid molecules were investigated as inhibitors against four tumor cell lines (BT20 human breast carcinoma, SK-Mel 128 melanoma, DU-145 prostate carcinoma, and A549 lung carcinoma) and porcine pancreatic lipase (PPL). Most of these compounds showed notable antitumor activities against the tested tumor cell lines, and compounds 8i and 8l showed the best anti-lipase activity of 99.30 +/- 0.56% and 99.85 +/- 1.21%, respectively, at a concentration of 10 mu M.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [115Z047]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK)This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under the project number of 115Z047. Authors thank to TUBITAK for this support

Synthesis of Some New 1,2,4-Triazole Derivatives Starting from 3-(4-Chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol with Anti-Lipase and Anti-Urease Activities

WOS: 000337692800002PubMed: 24532369In the present study, starting compound 4 was prepared by deamination of compound 2 in the presence of hypophosphorous acid and sodium nitrite. Treatment of compound 4 with ethyl bromoacetate produced ethyl[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetate (5), which was converted to the hydrazide derivative (6) by treatment with hydrazine hydrate. the reaction of compound 6 with aromatic aldehydes resulted in the formation of arylidene hydrazides (7). Treatment of 6 with CS2 in the presence of potassium hydroxide (KOH), followed by cyclization with hydrazine hydrate, afforded 4-amino-5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione (9). the condensation of 9 with appropriate aldehydes gave Schiff bases (10), which were converted into Mannich bases (11) in the presence of formaldehyde. All the synthesized compounds were screened for their anti-lipase and anti-urease activities. Compounds 7b, 7d, 11b, 11c, and 11d showed moderate-to-good lipase inhibitory effects compared to orlistat. Compounds 7b and 7d exhibited better anti-lipase activity. Furthermore, among the compounds tested, 11a and 11d were found to show high inhibitory effect against urease with IC50 values of 12.39 +/- 0.35 and 16.12 +/- 1.06 mu g/mL, respectively. Compound 11c showed moderate inhibitory activity. the Mannich base containing compound 11 may be a source of good leads for the synthesis of lipase and urease dual inhibitors.Karadeniz Technical University, BAP, TurkeyKaradeniz Technical University [10020]The support provided by Karadeniz Technical University, BAP, Turkey (Project No. 10020) is gratefully acknowledged

Synthesis, molecular docking and biological evaluation of some benzimidazole derivatives as potent pancreatic lipase inhibitors

emirik, mustafa/0000-0001-9489-9093WOS: 000425897800050PubMed: 29306066In this study, a new series of benzimidazole and bisbenzimidazole derivatives were prepared via the reaction of iminoester hydrochlorides and o-phenylenediamines and then screened for their lipase inhibition properties. Among the synthesized molecules, compounds 7a, 8a and 8c showed the best inhibitory effect against lipase enzyme with IC50 values of 1.72 +/- 0.12 mu M, 1.92 +/- 0.28 and 0.98 +/- 0.07 mu M, respectively. Moreover, molecular modeling studies were performed in order to understand to the inhibitory activity of the molecules. Binding poses of the studied compounds were determined at the target sites using induced fit docking (IFD) algorithms. (C) 2017 Elsevier Inc. All rights reserved.Recep Tayyip Erdogan University Scientific Research Project Unit (BAP)Recep Tayyip Erdogan University [FBA-2016-544]; Recep Tayyip Erdogan UniversityRecep Tayyip Erdogan UniversityThe authors declare no conflicts of interest. This work was supported by Recep Tayyip Erdogan University Scientific Research Project Unit (BAP) under project number of FBA-2016-544. Authors thank to Recep Tayyip Erdogan University for this support

Synthesis of Some Heterofunctionalized Penicillanic Acid Derivatives and Investigation of Their Biological Activities

Alpay Karaoglu, Sengul/0000-0003-1047-8350WOS: 000332331800006PubMed: 242934036-Substituted amino-penicillanic acid esters were synthesized starting with 6-apa. the compounds containing a 1,3-thiazole- or 1,3-thiazolidinone nucleus linked to the penicillanic acid skeleton via a hydrazino linkage were obtained from 6-apa. the treatment of carbonylamino and carbonothioylamino compounds with 4-chlorophenacyl bromide or ethyl bromoacetate gave 6-bis{4-[1,3-thiazol(idinone)amino]benzoyl}amino derivatives of 6-apa. Benzyl derivatives were synthesized in several steps, starting with 4-aminobenzoyl chloride. the treatment of 4-{[3-benzyl-4-oxo-1,3-thia(oxa)zolidin-2-ylidene]amino}benzoyl chlorides with 6-apa in ethanolic solution produced the 6-[bis(4-{[3-benzyl-4-oxo-1,3-thiazolidin-2-ylidene]amino}benzoyl)amino] derivative of penicillanic acid, while the reaction of the same intermediates in DMF gave the mono-substituted amino derivative of 6-apa. the synthesized compounds were screened for their biological activities, and some of them were found to possess good to moderate antimicrobial activity. Moreover, some of the compounds displayed antiurease, anti--lactamase, and/or antilipase activities.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [111T427]The support provided by Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 111T427) is gratefully acknowledged

Structure-Based Hybridization, Conventional and Microwave Irradiated Synthesis, Biological Evaluation and Molecular Docking Studies of New Compounds Derived from Thiomorpholin

WOS: 000395679300007Background: The amine 2 obtained via two steps starting from thiomorpholine was converted into the corresponding 1,3-thiazole (4), arylmethileneamino (5a- d) and hydrazide (7) derivatives using conventional and also microwave techniques. The synthesis of 1,3,4-oxadiazole (8), arylidenenhydrazide (9a-c) and carbothioamides (10a,b) was performed with the treatment of 7 with CS2, suitable amines and suitable isothiocyanates, respectively. Method: Moreover, the treatment of compounds 10a, b with ethylbromoacetate, 2-bromo-1-(4-chlorophenyl) ethanone, conc. H2SO4 and NaOH yielded the corresponding, 1,3-thiazolidinone (11a,b), 1,3-thiazole (12), 1,3,4-thiadiazole (13a,b) and 1,2,4-triazole (14) derivatives, respectively, by either conventional or microwave mediated conditions. The one-pot three component synthesis of fluoroquinolone derivatives (15a,b and 16) was performed by condensation between compounds 8 and 14 with norfloxacine and ciprofloxacine under conventional or microwave irradiation conditions. Results: The effects of different catalysts, solvents and microwave powers on conventional and microwave-prompted reactions was also examined. The synthesized compounds were screened for their antimicrobial, enzyme inhibition and antioxidant activities. Molecular docking of some of the synthesized compounds into the active sites of lipase, alpha-glucosidase and urease was also carried out in order to predict the binding affinity and non-covalent interactions between them.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [113Z181]The support provided by the Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 113Z181) is gratefully acknowledged

Synthesis and evaluation of alpha-glucosidase and pancreatic lipase inhibition by quinazolinone-coumarin hybrids

WOS: 000393034400007A new series of 2-substituted quinazolin-4(3H)-one derivatives including coumarin nucleus has been synthesized and screened for their lipase and a-glucosidase inhibition properties. Among the synthesized compounds, N'-{2-[2-(3,4-dichlorobenzyl)-4-oxoquinazolin-3(4H)-yl]acetyl}-2-oxo-2H-chromene-3-carbohydrazide and N'-{2-[2-(4-bromobenzyl)-4-oxoquinazolin-3(4H)-yl] acetyl}-2-oxo-2H-chromene-3-carbohydrazide showed the best inhibitory effect against a-glucosidase with IC50 values of 6.11 +/- 0.40 and 7.34 +/- 0.37 mu M, respectively. These compounds also showed strong anti-lipase activity (IC50 3.52 +/- 0.49 and 2.85 +/- 0.27 mu M, respectively).Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [115Z885]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK)This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under the project number of 115Z885. the authors gratefully thank TUBITAK for financial support

Primary Ovarian Monochorionic Twin Ectopic Pregnancy A Case Report

BACKROUND: Primary ovarian pregnancy is a rare form of ectopic gestation and one that is often diagnosed only at the time of surgery

Microwave Assisted Synthesis and Antimicrobial Activity Evaluation of New Heterofunctionalized Norfloxacine Derivatives

WOS: 000389464700011The synthesis of new hybrid compounds containing several heterocyclic groups namely norfloxacine, 1,2,4-triazole, 1,3,4-oxadiazole, piperazine, morpholine, thiomorpholine, 1,3,4-thiadiazole etc. was performed by conventional and successfully optimized microwave assisted techniques. The effect of acid catalyst on one pot tricomponent Mannich reaction was investigated as well. The structures of newly synthesized compounds were eluciated on the basis of spectroscopic techniques. Also, the synthesized compounds were screened for their antimicrobial activities and most of them were found to possess good-moderate antimicrobial activity.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [111T427, 113Z181]; Karadeniz Technical University, BAP, TurkeyKaradeniz Teknik University [8663]The support provided by Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 111T427 and 113Z181) and Karadeniz Technical University, BAP, Turkey (Ref. no. 8663) and is gratefully acknowledged