Synthesis and pharmacological activities of some new 2-[1-Heptyl-3-(4-methoxybenzyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl] acetohydrazide derivatives

WOS: 000347145200004In the present investigation, the key intermediate acetohydrazide derivative 5 was synthesized starting from 3-(4-methoxybenzyl)-4-amino-4,5-dihydro-1,2,4-triazol-5-one (1) by a four-step reaction. Thiosemicarbazides 6a-f and arylidenehydrazide derivatives 8a-d were obtained from compound 5. the cyclization of compounds 6a-f in the presence of NaOH resulted in the formation of compounds 7a-f. the compounds were characterized by IR, H-1 NMR, C-13 NMR spectroscopy, elemental analysis and mass spectial studies. the compounds were tested for their anti-lipase, anti-alpha-glucosidase and anti-mycobacterial activities. Compounds 6b and 8c exhibited excellent anti-lipase activity, and compound 8d showed excellent anti-alpha-glucosidase activity. Compounds 3 and 4 exhibited good anti-tuberculosis activity.Karadeniz Technical University, BAP, TurkeyKaradeniz Technical University [10020]The support provided by Karadeniz Technical University, BAP, Turkey (project no. 10020) is gratefully acknowledged

Microwave-assisted synthesis of some hybrid molecules containing penicillanic acid or cephalosporanic acid moieties and investigation of their biological activities

Alpay Karaoglu, Sengul/0000-0003-1047-8350WOS: 000334184400039Ethyl 4-amino-2-fluorophenylpiperazin-1-carboxylates containing a 1,3-oxazol(idin)e, 5-thioxo-1,2,4-triazole, 1,3,4-thiadiazole, 5-thioxo-1,3,4-oxadiazole, or 1,3-thiazole nucleus were obtained starting from ethyl piperazine-1-carboxylate (1) by several steps. the treatment of amine, 3 or hydrazide, 9 with several aromatic aldehydes generated the corresponding arylmethyleneamino (3a-f) or arylidenehydrazino (12a-c) compounds. the Mannich reaction between the 1,2,4-triazole or 1,3,4-oxadiazole compounds and 7-aca produced cephalosporanic acid derivatives. Penicillanic acid derivatives were obtained when 6-apa was used in the Mannich reactions. the synthesized compounds were screened for their antimicrobial, antilipase, and antiurease activities. Some of them were found to possess good-moderate antimicrobial activity against the test microorganisms. Two compounds exhibited antiurease activity, and four of them displayed antilipase activity.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [107T333]; Karadeniz Technical University, BAP, TurkeyKaradeniz Technical University [8623]This Project was supported by Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 107T333) and Karadeniz Technical University, BAP, Turkey (Ref. No. 8623) and is gratefully acknowledged

Cloning, expression, and characterization of a novel CTP synthase gene from Anoxybacillus gonensis G2

The cytidine-5'-triphosphate (CTP) synthase (EC 6.4.3.2) gene (pyrG) was cloned and sequenced from the thermophilic bacterium Anoxybacillus gonensis G2 (Ago). The gene is 1590 bp in length and encodes a protein of 530 amino acids, with a molecular mass of 59.5 kDa. The amino acid sequence of CTP synthase shares approximately 90%–94% similarity to Bacillus sp., and it belongs to the triad glutamine amidotransferases, which utilize a Cys–His–Glu triad for activity. Multiple sequence alignments revealed that the enzyme includes conserved amino acids responsible for catalytic activity and the binding of a divalent metal ion (Mg+2). AgoCTP synthase (AgoG2CTPs) was overproduced in Escherichia coli BL21 (DE3) pLysS as recombinant and purified by nickel affinity chromatography. Its biochemical characterization showed that the enzyme had maximal activity at pH 9.0–10.0 and 65 ºC. Km, Vmax, and kcat were found to be approximately 12.415 mM, 0.381 U/L, and 0.762 s–1 at 65 ºC, respectively. CTP synthase promotes the formation of CTP in dividing cells and is a recognized target for anticancer and antibacterial drugs. The results obtained from this study can be improved upon with the use of different species and substrates

Microwave-assisted and conventional synthesis of novel antimicrobial 1,2,4-triazole derivatives containing nalidixic acid skeleton

Carbothioamides 4a,b, obtained from nalidixic acid, were converted to the corresponding 1,3-thiazolidine derivatives 5a,b by cyclocondensation with 2-bromo-1-(4-chlorophenyl)ethanone. Treatment of 4a,b with base afforded 1,2,4-triazoles 6a,b. The synthesis of 1,3-oxazolidine 7 was performed by the reaction of compound 4a with ethyl bromoacetate. Treatment of 4a with acid produced 1,3,4-thiadiazole 8. The reaction of compounds 6a and 6b with several heterocyclic amines in the presence of formaldehyde gave the corresponding Mannich bases 9–15 containing various pharmacophore groups. Conventional and microwave-assisted methods were used for the synthesis. The effect of an acid catalyst on Mannich reactions was investigated. The structures of the newly synthesized compounds were elucidated on the basis of 1H NMR, 13C NMR, FTIR, EIMS techniques, and elemental analysis. All compounds were screened for their antimicrobial activity

Synthesis and study of alpha-glucosidase inhibitory, antimicrobial and antioxidant activities of some benzimidazole derivatives containing triazole, thiadiazole, oxadiazole, and morpholine rings

WOS: 000349913000004A new series of 2-(4-bromobenzyl)- and 2-(4-fluorobenzyl)-1H-benzimidazole derivatives containing 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole, and morpholine rings has been synthesized. the structures of the newly synthesized compounds were confirmed by H-1 and C-13 NMR and mass spectra, and all substances have been screened for their alpha-glucosidase inhibitory, antimicrobial and antioxidant activities. Hydrazide, oxadiazole, thiosemicarbazide, and 1,2,4-triazole-3-thiol derivatives showed very good ABTS scavenging activities (IC50 1.94-4.79 mu M). Oxadiazole and thiosemicarbazide derivatives also revealed notable DPPH scavenging activity. 5-[(2-(4-Bromobenzyl)-1H-benzimidazol-1-yl)methyl]-1,3,4-oxadiazole-2-thiol was found to be more potent than acarbose. 2-(4-Fluorobenzyl)-1H-benz- imidazole was effective against both Gram-positive and Gram-negative bacteria, especially, M. smegmatis.Recep Tayyip Erdogan University, BAP, TurkeyRecep Tayyip Erdogan University [2013.102.02.10]The authors gratefully acknowledge financial support from the Recep Tayyip Erdogan University, BAP, Turkey, through Project 2013.102.02.10

Microwave-promoted synthesis and biological activity of some 2-hetarylmethyl-4-(4-hetarylphenyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one derivatives

Ozil, Musa/0000-0002-1980-1364;WOS: 000352107700015A series of fused and non-fused 1,2,4-triazole derivatives were prepared starting from ethyl 4-[1-(2-ethoxy-2-oxoethyl)-3-methyl-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl]benzoate. Firstly, both ethyl ester groups were simultaneously transformed into hydrazide groups, then into 4-amino-5-mercapto-4H-1,2,4-triazol-3-yl groups using both microwave-assisted and conventional methods. the latter products interacted with 2 equiv of phenacyl bromides, chloroacetone, or chloroacetic acid to form ring assemblies containing two [1,2,4]triazolo-[3,4-b][1,3,4]thiadiazine fragments. Cyclization using 2 equiv of carboxylic acids, urea, or CS2 leads to the corresponding [1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole derivatives. the synthesized compounds were evaluated in regard to their antimicrobial, anti-lipase, and antiurease activities.Scientific and Technical Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112T640]Financial support provided by the Scientific and Technical Research Council of Turkey (TUBITAK) through project 112T640 is gratefully acknowledged

Molecular docking studies and synthesis of novel bisbenzimidazole derivatives as inhibitors of alpha-glucosidase

emirik, mustafa/0000-0001-9489-9093; Ozil, Musa/0000-0002-1980-1364WOS: 000386990200011PubMed: 27576293A series of bisbenzimidazole derivatives starting from o-phenylenediamine and 4-nitro-o-phenylenediamine were prepared with oxalic acid. Most of the reactions were conducted using both the microwave and conventional methods to compare yields and reaction times. the operational simplicity, environmental friendly conditions and high yield in a significantly short reaction time were the major benefits. All substances' inhibitory activities against alpha-glucosidase were evaluated. the results may suggest a significant role for the nature of bisbenzimidazole compounds in their inhibitory action against alpha-glucosidase. They showed different range of alpha-glucosidase inhibitory potential with IC50 value ranging between 0.44 +/- 0.04 and 6.69 +/- 0.01 mu M when compared to the standard acarbose (IC50, 13.34 +/- 1.26 mu M). This has described a new class of alpha-glucosidase inhibitors. Molecular docking studies were done for all compounds to identify important binding modes responsible for inhibition activity of alpha-glucosidase. (C) 2016 Elsevier Ltd. All rights reserved.Scientific and Technical Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [113Z902]The authors gratefully acknowledge the financial support from the Scientific and Technical Research Council of Turkey (TUBITAK) through Project 113Z902

Microwave-assisted synthesis of some new coumarin derivatives including 1,2,4-triazol-3-one and investigation of their biological activities

WOS: 000358138200005By using the microwave technology, a new protocol has been developed for the synthesis of new coumarin derivatives including 1,2,4-triazol-3-one skeleton. This protocol proves to be efficient and environmentally friendly in terms of easy work-up and good yields. All newly synthesized compounds were screened for their antimicrobial activity and lipase inhibition. Most of the compounds were found to be effective on Escherichia coli. N'-{[4-Amino-3-(2-bromobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetyl}-6-bromo-2-oxo-2Hchromene-3-carbohydrazide and N'-{[4-amino-3-(3,4-dichlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetyl}-6-bromo-2-oxo-2H-chromene-3-carbohydrazide had a good effect on lipase inhibition

Topraktan izole edilen Trichoderma harzianum hücre dışı lipazının izolasyonu, üretimi ve karakterizasyonu

Bu çalışma, Trichoderma harzianum lipazının karakterizasyonu hakkında ilk rapordur. Yeni bir suş olan Trichoderma harzianum IDM14D topraktan izole edildi. İzole edilen bu suş, lipaz üretimi için çalkalamalı kültürde 30 °C’de 7 gün inkübe edilmiştir. Lipaz üretimi için en iyi karbon kaynağı glukoz, en iyi azot kaynağının pepton olduğu belirlendi. Maksimum biyokütle üretimi 7 gün sonunda 1,25 g/L olarak belirlendi. Enzimin en iyi aktivite gösterdiği pH 8,5, sıcaklık 40 °C olarak belirlendi. T. harzianum lipazı pH 8,0-10,0 aralığında 40 °C’de 60 dakika kararlılığını koruduğu belirlendi. Ca2+ ve Mn2+ iyonlarının lipaz aktivitesini artırdığı, fakat diğer metal iyonlarının enzim aktivitesini etkilemediği gözlendi. p-nitrofenil butirat hidrolizi ile ölçülen ham enzimin Km ve Vmaks değerleri sırasıyla 7,15 mM ve 7,067 mM/dk olarak belirlendi.This is the first report about the characterization of Trichoderma harzianum lipase. A novel strain of Trichoderma harzianum IDM14D was isolated from soil. The isolated strain was cultivated for lipase production in shake fl asks at 30 ºC for 7 days. For lipase production, it was determined that the best carbon source was glucose and the best nitrogen source was peptone. Maximum biomass was produced at a concentration of 1.25 g/L, in 7 days. The optimum pH and temperature for activity of the enzyme were 8.5 and 40 ºC, respectively. The lipase was stable at a pH range of 8.0-10.0 and at 40 ºC for 60 min. Ca2+ and Mn2+ enhanced lipase activity but it was determined that other metallic ions did not affect the enzyme activity. The Km and Vmax values of the crude enzyme for p-nitrophenyl butyrate hydrolysis were found to be 7.15 mM and 7.067 mM/min, respectively

Rapid synthesis and lipase inhibition activity of some new benzimidazole and perimidine derivatives

WOS: 000336054000013This study presents a synthesis of new series of some benzimidazole, bisbenzimidazole and perimidine derivatives via microwave technique, which, leads to the good product yields and short reaction times. the structure of newly synthesized compounds was confirmed by H-1 NMR and C-13 NMR spectra. These compounds were screened for their lipase inhibition activity. Then, all compounds were evaluated with regard to pancreatic lipase activity, and some of the 2-substituted perimidines, bisperimidine and bisbenzimidazole derivatives showed lipase inhibition at various concentrations