Synthesis and antioxidant activity of peptide-based ebselen analogues

A series of di- and tripeptide-based ebselen analogues has been synthesized. The compounds were characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2) , tert-butyl hydroperoxide (tBuOOH), and cumene hydroperoxide (Cum-OOH) as substrates, and glutathione (GSH) as a cosubstrate. Although all the peptide-based compounds have a selenazole ring similar to that of ebselen, the GPx activity of these compounds highly depends on the nature of the peptide moiety attached to the nitrogen atom of the selenazole ring. It was observed that the introduction of a phenylalanine (Phe) amino acid residue in the N-terminal reduces the activity in all three peroxide systems. On the other hand, the introduction of aliphatic amino acid residues such as valine (Val) significantly enhances the GPx activity of the ebselen analogues. The difference in the catalytic activity of dipeptide-based ebselen derivatives can be ascribed mainly to the change in the reactivity of these compounds toward GSH and peroxide. Although the presence of the Val-Ala-CO(2) Me moiety facilitates the formation of a catalytically active selenol species, the reaction of ebselen analogues that has a Phe-Ile-CO(2) Me residue with GSH does not generate the corresponding selenol. To understand the antioxidant activity of the peptide-based ebselen analogues in the absence of GSH, these compounds were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. In contrast to the GPx activity, the PN-scavenging activity of the Phe-based peptide analogues was found to be comparable to that of the Val-based compounds. However, the introduction of an additional Phe residue to the ebselen analogue that had a Val-Ala dipeptide significantly reduced the potency of the parent compound in PN-mediated nitration.     

Antioxidant activity of the anti-inflammatory compound ebselen: a reversible cyclization pathway via selenenic and seleninic acid intermediates

A revised mechanism that accounts for the glutathione peroxidase (GPx)-like catalytic activity of the organoselenium compound ebselen is described. It is shown that the reaction of ebselen with H(2)O(2) yields seleninic acid as the only oxidized product. The X-ray crystal structure of the seleninic acid shows that the selenium atom is involved in a noncovalent interaction with the carbonyl oxygen atom. In the presence of excess thiol, the Se--N bond in ebselen is readily cleaved by the thiol to produce the corresponding selenenyl sulfide. The selenenyl sulfide thus produced undergoes a disproportionation in the presence of H(2)O(2) to produce the diselenide, which upon reaction with H(2)O(2), produces a mixture of selenenic and seleninic acids. The addition of thiol to the mixture containing selenenic and seleninic acids leads to the formation of the selenenyl sulfide. When the concentration of the thiol is relatively low in the reaction mixture, the selenenic acid undergoes a rapid cyclization to produce ebselen. The seleninic acid, on the other hand, reacts with the diselenide to produce ebselen as the final product. DFT calculations show that the cyclization of selenenic acids to the corresponding selenenyl amides is more favored than that of sulfenic acids to the corresponding sulfenyl amides. This indicates that the regeneration of ebselen under a variety of conditions protects the selenium moiety from irreversible inactivation, which may be responsible for the biological activities of ebselen.     

Synthesis, structure, and glutathione peroxidase-like activity of amino acid containing ebselen analogues and diaryl diselenides

The synthesis of some ebselen analogues and diaryl diselenides, which have amino acid functions as an intramolecularly coordinating group (Se···O) has been achieved by the DCC coupling procedure. The reaction of 2,2'-diselanediylbis(5-tert-butylisophthalic acid) or the activated ester tetrakis(2,5-dioxopyrrolidin-1-yl) 2,2'-diselanediylbis(5-tert-butylisophthalate) with different C-protected amino acids (Gly, L-Phe, L-Ala, and L-Trp) afforded the corresponding ebselen analogues. The used precursor diselenides have been found to undergo facile intramolecular cyclization during the amide bond formation reaction. In contrast, the DCC coupling of 2,2'-diselanediyldibenzoic acid with C-protected amino acids (Gly, L/D-Ala and L-Phe) affords the corresponding amide derivatives and not the ebselen analogues. Some of the representative compounds have been structurally characterized by single-crystal X-ray crystallography. The glutathione peroxidase (GPx)-like activities of the ebselen analogues and the diaryl diselenides have been evaluated by using the coupled reductase assay method. Intramolecularly stabilized ebselen analogues show slightly higher maximal velocity (V(max)) than ebselen. However, they do not show any GPx-like activity at low GSH concentrations at which ebselen and related diselenides are active. This could be attributed to the peroxide-mediated intramolecular cyclization of the corresponding selenenyl sulfide and diaryl diselenide intermediates generated during the catalytic cycle. Interestingly, the diaryl diselenides with alanine (L,L or D,D) amide moieties showed excellent catalytic efficiency (k(cat)/K(M)) with low K(M) values in comparison to the other compounds.     

A simple and efficient strategy to enhance the antioxidant activities of amino-substituted glutathione peroxidase mimics

The glutathione peroxidase (GPx) activities of some diaryl diselenides incorporating tertiary amino groups were studied with H(2)O(2), Cum-OOH, and tBuOOH as substrates and with PhSH as thiol co-substrate. Simple replacement of a hydrogen atom with a methoxy group dramatically enhances the GPx activity. The introduction of methoxy substituents ortho to selenium in N,N-dialkylbenzylamine-based compounds makes the basicity of the amino groups perfect for the catalysis. The presence of 6-OMe groups prevents possible SeN interactions in the selenols, increasing their zwitterionic characters. The methoxy substituents also protect the selenium in the selenenic acid intermediates from overoxidation to seleninic acids or irreversible inactivation to selenonic acid derivatives. The additional substituents also play a crucial role in the selenenyl sulfide intermediates, by preventing thiol exchange reactions-which would normally lead to an inactivation pathway-at the selenium centers. The strengths of SeN interactions in the selenenyl sulfide intermediates are dramatically reduced upon introduction of the methoxy substituents, which not only reduce the thiol exchange reactions at selenium but also enhance the nucleophilic attack of the incoming thiols at sulfur. The facile attack of thiols at sulfur in the selenenyl sulfides also prevents the reactions between the selenenyl sulfides and H(2)O(2) that can regenerate the selenenic acids (reverse-GPx cycle). These studies reveal that the simple 6-OMe groups play multiple roles in each of the catalytically active intermediates by introducing steric and electronic effects that are required for efficient catalysis.     

Synthesis,characterization, and antioxidant activity of heterocyclic Schiff bases

Schiff base derivatives have gained great importance due to revealing a great number of biological properties. Schiff bases were synthesized by treatment of 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 1 ) with various aldehydes in methanol at reflux. In addition, diamine was reacted with an aldehyde to yield the corresponding Schiff bases. The structures of synthesized Schiff bases were elucidated by spectroscopic methods such as microanalysis, ¹H-NMR, ¹³C-NMR, and FTIR. Antioxidant activities of synthesized Schiff bases were carried out using different antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^•) scavenging, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, and reducing power activity. (E)-4-((1H-indol-3-yl)methyleneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 3 ), (E)-1,5-dimethyl-4-((2-methyl-1H-indol-3-yl)methyleneamino)-2-phenyl-1H-pyrazol-3(2H)-one ( 5 ), (E)-1,5-dimethyl-2-phenyl-4-(thiophen-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 7 ), (E)-1,5-dimethyl-2-phenyl-4-(quinolin-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 9 ), (1S,2S,N1,N2)-N1,N2-bis((1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 11 ), and (1S,2S,N1,N2)-N1,N2-bis((2-methyl-1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 12 ) were synthesized in high yields. Compound 5 displayed a good ABTS^•+ activity. Compound 3 revealed the outstanding activity in all assays. Compound 7 has the best-reducing power ability in comparison to other synthesized compounds. Although compounds 5, 11, 12 are new, compounds 3, 7, 9 are known. Due to revealing a good antioxidant activity, the synthesized compounds ( 3, 5, 7 ) have the potential to be used as synthetic antioxidant agents.     

Synthesis,antioxidant and antitumor activities of some of new cyclobutane containing triazoles derivatives

Abstract

Thiosemicarbazides (2a–e) were obtained by the interaction of furan-2-carboxylic acid hydrazide (1) with five different isothiocyanate (RNCS) derivatives. By addition of KOH to the reaction medium, ethyl, allyl, phenyl and benzyl, p-tolyl substituted 1,2,4-triazoles (3a–e) were obtained. 3a–e were dissolved in dry acetone containing K₂CO₃ in the presence of 2-chloro-1-(3-methyl-3-mesitylcyclobutyl) ethanone (4) to give 3,4,5-trisubstituted 1,2,4-triazole sulfanyl compounds containing a cyclobutane ring (5a–e). The structures of the final compounds were confirmed by elemental analyses, FT-IR, ¹H-NMR and ¹³C-NMR. The antioxidant and antitumor properties of the synthesized compounds were also investigated. Three of the triazole derivatives with p-tolyl, benzyl and phenyl substituents (5c–e) displayed good antioxidant and antitumor activity in comparison to the standards.     

超支化分子桥联受阻酚抗氧化剂的合成与表征

以正十八胺为核的1.0代超支化大分子和β-(3,5-二叔丁基-4-羟基苯基)丙酰氯为原料,通过酰胺化缩合反应,合成了一种具有长链烷基和2个受阻酚基团的新型超支化分子桥联受阻酚类抗氧化剂.通过正交实验确定了超支化分子桥联受阻酚类抗氧化剂的最佳合成体系为:3,5-丙酰氯为酰化剂、K_2CO_3为缚酸剂、苯和水为反应溶剂.通过条件优化实验确定了超支化分子桥联受阻酚类抗氧化剂的最佳合成条件为:3,5-丙酰氯与1.0代超支化大分子的物质的量比为6∶1、反应温度为25 ℃、反应时间为12 h、体系苯与水体积比为6∶1、3,5-丙酰氯与缚酸剂K_2CO_3的物质的量比为1∶1,在此条件下,超支化分子桥联受阻酚类抗氧化剂的收率高达75.5%.FT-IR和1H NMR证实了合成抗氧化剂的化学结构与其理论结构相符.超支化分子桥联受阻酚类抗氧化剂在聚乙烯树脂中的抗氧化性能优于抗氧化剂1076,且随着烷基链长度的增加,抗氧化性能增强.     

Formation of diaryl sulfides and sulfoxides: Synthesis,characterization and structure activity correlation studies

Abstract

The synthesis of a series of stable diarylsulfides and sulfoxides is reported. All the newly synthesized compounds were characterized by ¹H, ¹³C NMR and mass spectroscopic techniques. A detailed mechanistic study indicates that the formation of sulfoxides follows the oxidation. In addition to synthesis, characterization and mechanistic studies, the glutathione peroxidase(GPx) mimetic activity of the newly synthesized compounds is described. It is observed that the diaryl sulfides having a heterocyclic ring attached to the nitrogen atom facilitates the oxidation of the sulfur center to form the corresponding sulfoxides. The substituents attached to the nitrogen atom play an important role in the catalytic activity of the substituted diaryl sulfides. The obtained data supports for the higher antioxidant activity of diaryl sulfides than that of the corresponding sulfoxides.     

Synthesis,characterization, antioxidant properties and DFT calculation of some new pyrimidine derivatives

Abstract

In this study, 5-benzoyl-4-(4-(methylthio)phenyl)-6-phenyl-1,2,3,4-tetrahydro-2-thioxo (1), oxo (2) and imino (3) pyrimidine derivatives were prepared via Multicomponent Cyclocondensation Reactions (MCRs). The compounds thiazolo[3,2-a]pyrimidin-3(5H)-one (4) and thiazin-4(6H)-one (5) were obtained via the reaction of compound 1 with bromoacetic acid and 3-bromopropionic acid, respectively. Structures were determined by using FT-IR, ¹H/¹³C NMR and elemental analyses. Also the compounds 4 and 5 were analyzed by X-ray single crystal analysis. All compounds were investigated as corrosion inhibitors using density functional theory (DFT) at the level of B3LYP/6-31G (d, p). According to the calculations, the compound 3 appears to be a good inhibitor for corrosion. On the other hand, total antioxidant properties were measured in vitro by DPPH^?, ABTS^?+ test, hemolysis of phenylhydrazine erythrocytes and metal chelating effect. The results were compared with standard antioxidants such as trolox and α-tocopherol. These data revealed that compounds 1, 2 and 5 are more active with respect to 3 and 4 in scavenging the radicals.     

Synthesis,structural characterization,antimicrobial, antioxidant and DNA binding studies of some novel homo‐binuclear Schiff base metal (II) complexes

A novel bi‐nucleating Schiff base ligand, 6,6′‐(((1E,1′E)‐thiophene‐2,5‐diylbis (methaneylylidene))bis (azaneylylidene))bis (3,4‐dimethylaniline), and five binuclear M (II) complexes were synthesized. The bi‐nucleating Schiff base ligand and its metal complexes were characterized using various physicochemical techniques, e.g. elemental analyses, spectroscopic methods, conductivity and magnetic moment measurements. The low molar conductance of the complexes in dimethylsulfoxide shows their non‐electrolytic nature. The antibacterial activities were screened against pathogenic bacteria (Staphylococcus aureus, Escherichia coli, Pseudomonas putida and Bacillus subtilis). The antifungal activity was screened against Aspergillus niger, Aspergillus flavus and Rhizoctonia bataicola. The antimicrobial activity data showed that the metal complexes are more potent than the parent Schiff base ligand against microorganisms. The antioxidant activities of the synthesized compounds were investigated through scavenging activity against 2,2‐diphenyl‐2‐picrylhydrazyl, superoxide anion, hydroxyl and 2,2′‐ azinobis (3‐ethylbenzothiazoline‐6‐sulfonic acid) radicals. The complexes have superior radical scavenging activity than the free ligand and the scavenging effects of the Cu (II) complex are stronger than those of the other complexes. DNA binding studies were performed using electronic spectroscopy, fluorometric competition studies and viscosity measurements. The data indicated that there is a marked enhancement in biocidal activity of the ligand under similar experimental conditions because of coordination with metal ions.     

Synthesis and evaluation of pyrazole‐incorporated monocarbonyl curcumin analogues as antiproliferative and antioxidant agents

A series of pyrazole‐incorporated monocarbonyl analogues of curcumin were synthesized via Clasien–Schimidt‐type condensation and subsequently screened for in vitro antiproliferative and antioxidant activity. The analogues 4c, 5d, 5e, 5g, 6e, and 6f showed potential activity against the MDA‐MB‐231 cell line. The synthesized analogues were also screened for their antioxidant activity. Compounds 5a , 5e , 6d, and 6f exhibit comparable radical scavenging activity with respect to the standard drug ascorbic acid. Furthermore, a molecular docking study has been conducted for 5d and 5g and suggests that these compounds have a potential to become lead molecules in drug discovery and process.     

Synthesis,cytotoxicity assessment and antioxidant activity of some new thiazol-2-yl carboxamides

Dependence on the biological activity of 2-aminothiazole, the synthesis and chemical reactions of ethyl 3-oxo-3-(thiazol-2-ylamino)propanoate ( 1 ) with some different reagents were described for cytotoxic and antioxidant evaluation. The new derivatives 2–19 could be synthesized and characterized by correct analytical and spectral data. In addition to the thiazole ring, these compounds contain 2H-1,2,3-triazole ( 3 ), 1H-pyrazole ( 5 , 12 ), 1,3-dithiane ( 7 ), benzothiazole ( 10 ), thiazolidine ( 13 ), thiazolidinone ( 14 , 15 ), 2H-chromene ( 17 ), pyridine ( 19 ) moieties. The preparation of compounds 2–19 was performed through the formation of the isolable 2-(2-phenylhydrazineylidene) 2 , 2-dimethylaminomethylidene 4 , 2-phenylcarbamothioyl 9 , 2-(methylthio)(phenylamino) methylidene 11 and non-isolable potassium bis(thiolate) 6 , potassium thiolate 8 intermediates from precursor 1 . The activity of these derivatives 1–19 against human lung fibroblast (WI38) and human prostate cancer (PC3) were examined in vitro using the MTT assay. The assessment of their antioxidant activities was carried out by following the ABTS method to evaluate their pharmaceutical importance.     

Synthesis,characterization, in-vitro biocidal and nuclease activity of some coordination compounds

Complexes of Cu(II), Fe(II) and Fe(III) have been synthesized with 2-nitro-3,3′-benzylidene bis[4-hydroxycoumarin]/4-chloro-3,3′-benzylidene bis[4-hydroxycoumarin]/4-hydroxy-3,3′-benzylidene bis[4-hydroxycoumarin]. They have been characterized using ¹H-NMR, ¹³C-NMR, IR spectra, electronic spectra, magnetic measurements, elemental analyses and screened for their in-vitro biocidal activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Serratia marcescens bacterial strains and for their in-vitro antifungal activity against Aspergillus niger, Aspergillus flavus and Lasiodiplodia theobromae. The metal complexes exhibit good activity against bacterial strains compared to parent compounds, but no significant antifungal activity against fungal strains. In-vitro nuclease activity has been carried out using agarose gel electrophoresis. The synthesized compounds show effective nuclease activity.     

北虫草多糖的理化特征及抗氧化和免疫活性研究

采取超高压提取,DEAE-Sepharose Fast Flow和Sephadex G-100柱层析分离纯化得到虫草多糖(CMP),通过高效凝胶色谱(HPGPC)、气相色谱(GC)和傅里叶红外光谱(FT-IR)对其理化特征进行了表征,并对CMP抗氧化及免疫调节活性进行了测定.结果显示CMP是纯度较高杂多糖,由鼠李糖、甘露糖、葡萄糖和半乳糖4个单糖组成,结果表明超高压是一种高效的菌多糖提取技术,提取得到的CMP可以探索作为天然的抗氧化和免疫调节剂应用于功能食品和药品.     

Synthesis, characterization, and biological evaluation of novel ferrocene-triadimefon analogues

In order to improve biological behavior of the 1H-1,2,4-triazole derivatives, a series of new ferrocene-analogues of commercial triadimefon were synthesized and their antifungal and plant growth regulatory activities evaluated. These organometallic analogues showed lower antifungal activity than parent triadimefon, but exhibited promising plant growth regulatory activity.     

Synthesis,antioxidant, and anticholinesterase activities of novel N-arylsulfonyl hydrazones bearing sulfonate ester scaffold

In this research, two new series of N-arylsulfonyl hydrazone compounds ( 14 – 25 ) possessing a sulfonate moiety were synthesized and characterized by elemental analysis and various spectroscopic techniques including fourier transform infrared (FT-IR), ¹H-, and ¹³C nuclear magnetic resonance (NMR). These compounds synthesized as target molecules ( 14 – 25 ) were tested for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities and antioxidant potential. The antioxidant capacities of the tested molecules were determined by four different assays. The IC₅₀ values of the screened molecules were determined in the range of 60.14 ± 0.25–84.81 ± 1.09 μM against AChE and in the range of 70.11 ± 0.67–93.60 ± 0.47 μM against BChE. In the AChE assay, 4-hydroxybenzaldehyde-based compound 25 (60.14 ± 0.25 μM) showed the highest activity in comparison to rivastigmine (501 ± 3.08 μM). This compound (71.42 ± 0.19 μM) is also one of the compounds with the highest activity against BChE. In the BChE assay, 2-hydroxybenzaldehyde-based compound 19 (70.11 ± 0.67 μM) indicated the highest activity in comparison to rivastigmine (19.95 ± 0.20 μM). In antioxidant activity studies, the tested molecules showed lower activities than the standard compounds (butylated hydroxytoluene and α-tocopherol). Consequently, some novel compounds can be used as potential inhibitor candidates in future studies.     

Novel 2-formylpyridine 4-allyl-S-methylisothiosemicarbazone and Zn(II), Cu(II), Ni(II) and Co(III) complexes: Synthesis,characterization, crystal structure,antioxidant, antimicrobial and antiproliferative activity

New zinc (II), copper (II), nickel (II) and cobalt (III) complexes, [Zn (HL)₂]I₂ (1) , [Cu (HL)Cl₂] (2) , [Cu (HL)Br₂] (3) , [Cu (HL)(H₂O)₂](ClO₄)₂ (4) , [Ni (HL)₂]I₂·H₂O (5) , [Co(L)₂]Cl (6) , [Co(L)₂]NO₃ (7) , [Co(L)₂]I·[Co(L)₂](I₃) (8) were obtained with 2-formylpyridine 4-allyl-S-methylisothiosemicarbazone ( HL ). The isothiosemicarbazone ligand was characterized by NMR (¹H and ¹³C), IR spectroscopy and X-ray diffraction. All the complexes were characterized by elemental analysis, IR, UV–Vis, ESI-MS spectroscopy, molar conductivity, magnetic susceptibility measurements. X-ray diffraction analysis on the monocrystal and powder elucidated the structure of the complexes 1 , 5 , 7 and 8 . The ligand and the complexes were tested for their antioxidant and antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Candida albicans. Also, the antiproliferative properties of these compounds on human leukemia HL-60, human cervical epithelial HeLa, human epithelial pancreatic adenocarcinoma BxPC-3, human muscle rhabdomyosarcoma spindle, large multinucleated RD cells and normal MDCK cells have been investigated. The nickel complex 5 and cobalt complexes 6 , 7 showed promising antiproliferative activity and low toxicity.     

Synthesis,characterization, and anticancer activity of some metal complexes with a new Schiff base ligand

A new Schiff base ligand, 2-((E)-((4-(((E)-benzylidene)amino)phenyl)imino)methyl)-naphthalene-1-ol, was prepared by the reflux condensation of p-phenylenediamine with 2-hydroxy-1-naphthaldehyde and benzaldehyde. Metal complexes were prepared by reacting the ligand with metal salts: VCl₃, CrCl₃·6H₂O, MnCl₂·3H₂O, FeCl₃·6H₂O, CoCl₃·6H₂O, NiCl₂·6H₂O, CuCl₂·2H₂O, and ZnCl₂. The ligand and its metallic complexes were characterized by various techniques such as elemental analysis, AAS, NMR, IR, UV–Vis, TGA, DTA, XRD and TEM. The data confirmed that the ligand coordinated with the metal ions in a bidentate nature, bonding through its azomethine nitrogen atom and phenolic oxygen atom; this gave an octahedral geometry. The XRD patterns of the complexes indicated that they were of various structures: the Mn(II), Co(III), and Cu(II) complexes were triclinic, the ligand and Ni(II) complex were orthorhombic, the V(III) and Zn(II) complexes were hexagonal, the Cu(II) complex was monoclinic, and the Fe(II) complex was cubic. TEM analysis confirmed that the complexes were nanoscale in nature. The antibacterial and antifungal activities of the ligand and its complexes against Salmonella enterica serovar typhi and Candida albicans were investigated by the hole plate diffusion method. It was observed that the Co(II) and Zn(II) complexes had intermediate antibacterial activities, while the V(III) complex had the highest activity against C. albicans fungi. The in vitro anticancer activities of the ligand and its metal complexes were tested towards PC-3, SKOV3, and HeLa tumour cell lines, where they exhibited higher antitumour activities against these selected human cell lines than clinically used drugs such as cisplatin, estramustine, and etoposide.