Synthesis and antioxidant capacities of some new benzimidazole derivatives

In this study, we prepared some new oxadiazolyl benzimidazole derivatives and investigated their antioxidant properties by determination of microsomal NADPH-dependent inhibition of lipid peroxidation levels (LP assay) and microsomal ethoxyresorufin O-deethylase activity (EROD assay). Some of these compounds 20, 23 had slightly inhibitory effects (28%) on the lipid peroxidation levels at 10(-3 )M concentration lower than standard BHT (65%). 5-[2-(Phenyl)-benzimidazol-1-yl-methyl]-2-mercapto-[1,3,4]-oxadiazole 16 was found to be more active than caffeine on the ethoxyresorufin O-deethylase activity with an IC(50 )value of 2.0 6 10(-4 )M.     

Synthesis and antioxidant evaluation of some new pyrazolopyridine derivatives

4,6-Dimethyl-1H-pyrazolo[3,4-b]pyridine-3-amine (1) was used as a key intermediate for the synthesis of imidazolopyrazole derivatives 7-11 upon interaction with 3-(2-bromoacetyl)-2H-chromen-2-one (2), 2-(benzothiazol-2-yl)-4-chloro-3-oxobutanenitrile (3), 2,3-dibromonaphthalene-1,4-dione (4), naphtha[2,3-b]oxirene-2,7-dione (5), 2,5-dichloro-3,6-dihydroxyhexa-2,5-diene-1,4-dione (6), respectively. Acetylation of 11 afforded the bis-acetyl 12. Also, the imidazolopyrimidine 15 was prepared via treatment of 1 with sodium 3,4-dioxo-3,4-dihydronaphthalene-1-sulfonate (13) in DMF followed by cyclization of the bis-pyrazolopyrimidine 14 with glacial acetic acid. On the other hand, compound 1 was reacted with (E)-1-(4-methoxyphenyl)-5-(piperidin-1-yl)pent-1-en-3-one hydrochloride (16), 2-hydroxy-3-((piperidin-1-yl)-methyl)-naphthalene-1,4-dione (17), 2-styryl-2H-indene-1,3-dione (18), enaminone 22, chloroquinoline-3-carbaldehyde 27a, chloroquinoline-(6-methyl)-3-carbaldehyde 27b and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (28) to afford pyrazolo[3,4-a]pyrimidines 19-21, 23, 29a, 29b and 30, respectively. Also, the pyrazolopyrimidinone 33 was obtained via treatment of 1 with 1-cyanoacetyl-3,5-dimethylpyrazole (31) followed by cyclization of the formed intermediate 32 with glacial acetic acid. Finally, treatment of 1 with o-terephthalaldehyde in glacial acetic acid afforded diazepine 34. The newly synthesized compounds were screened for their antioxidant properties in which some of them exhibited promising activities. Compounds 1, 14, 15, 23, 26, 29a, 30 and 32 have the ability to protect DNA from the damage induced by bleomycin.     

Synthesis and antioxidant properties of some indole ethylamine derivatives as melatonin analogs

The synthesis and lipid peroxidation (LP) inhibition activity of several novel indole melatonin analogues are reported. Compounds have shown variable antioxidant features depending on the substitution pattern. Melatonin and the antioxidant reference compound butyl hydroxy toluen (BHT) were used to compare the antioxidant capability of the compounds synthesized.     

Synthesis and in vitro antioxidant activity of some new fused pyridine analogs

A new series of pyrano[3,2-c]pyridines, pyrazolo[4,3-c]pyridines, and pyrido[4,3-d]pyrimidines were synthesized and screened for their in vitro antioxidant activity. Compounds 13, 14, 15, 23, 29, 30, and 31 exhibited the most active oxygen free-radical scavenger activity with percentage inhibitions of 99.4, 99.6, 99.8, 97.3, 99.0, 99.3, and 99.5%; respectively, which is comparable to the curcumin potency. Most of the tested compounds proved to be safe towards peripheral multinuclear neutrophils (PMNs). The detailed synthesis and antioxidant activity data are reported.     

Synthesis and antioxidant activity of curcumin analogs

Numerous biological activities including antioxidant, antitumor, anti-inflammation, and antivirus of the natural product curcumin were reported. However, the clinical application of it was significantly limited by its instability, poor solubility, less body absorbing, and low bioavailability. This review focuses on the structure modification and antioxidant activity evaluation of curcumin. To study the structure–activity relationship (SAR), five series of curcumin analogs were synthesized and their antioxidant activity were evaluated in vitro. The results showed that electron-donating groups, especially the phenolic hydroxyl group are an essential component to improve the antioxidant activity.     

3-硝基-2H-色烯衍生物的合成及抗菌活性研究

目的设计并合成一系列3-硝基-2H-色烯衍生物,研究其抗菌活性与构效关系。方法以水杨醛和2-硝基乙醇为原料合成目标化合物,采用肉汤稀释法测定抗菌活性。结果目标化合物结构均经过1HNMR和HRMS确证,3-硝基-2H-色烯衍生物对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌具有很好的抑制活性(MIC=4μg·mL-1)。结论 3-硝基-2H-色烯衍生物具有进一步深入研究的价值。     

Synthesis and anti-measles virus activity of new isoquinolin-4-one derivatives

Despite intense efforts to increase vaccine coverage, measles virus (MV) still causes significant morbidity and mortality in the world sometimes as a results of severe, chronic and lethal diseases. In an effort to develop therapies to supplement immunization strategies a number of 1-oxo-2-[[(1E)-phenylmethylene]amino]-1,2-dihydroisoquinoline-4-carboxylic acid derivatives were synthesized and evaluated for anti-measles activity. The substituents on the aromatic ring were chosen in order to evaluate the influence of electron-withdrawing or electron-donating effects on the electronic density of the aromatic moiety. We also evaluated the introduction of a vinyl chain between the exocyclic nitrogen and phenyl moiety. The biological results allow to outline some preliminary considerations on structure-activity relationship.     

Synthesis of new hydantoin-3-ethanethiol derivatives

5-sec-Butylthiomethyl-5-alkyl (methyl or phenyl) hydantoins (3−x) were prepared by the reaction of sec-butylthiomethyl alkyl (methyl or phenyl) ketone (1–2), potassium cyanide and ammonium carbonate. 3-(2-Bromoethyl) hydantoins (5–6) were the reaction products of 5-sec-butylthiomethyl-5-alkyl (methyl or phenyl) hydantoin and 1,2-dibromoethane in the presence of potassium hydroxide. Alkylation of5 and6 with an excess of alkyl (methyl or ethyl) iodide in THF with sodium hydride as base gave three 1-alkyl (methyl or ethyl)-3-(2-bromoethyl) hydantoins (7–9). Treatment of the 2-bromoethyl group with potassium thioacetate and triethylamine gave three 1-alkyl (methyl or ethyl)-3-(2-acetylthioethyl) hydantoins (10–12). Hydrolysis of the 2-acetylthioethyl group with sodium hydroxide in methanol afforded the three 1-alkyl (methyl or ethyl)-3-(2-mercaptoethyl) hydantoins.     

Synthesis and antioxidant activity of a new class of bis and tris heterocycles

A series of novel heterocycles, bisbenzoxazolyl/benzothiazolyl/benzimidazolyl pyrazoles/isoxazoles/pyrimidines were synthesized and evaluated for their antioxidant activity. The bisbenzoxazolylisoxazole 10 exhibited good antioxidant activity when compared with the standard ascorbic acid.     

Synthesis and antioxidant activity of substituted-1,3,2-diazaphosphole 1-oxides

Synthesis of 1-substituted-1,3,2-diazaphosphole 1-oxides (3a-l) were accomplished via a two-step process. It involves the preparation of diazaphospholo 1-oxide monochloride intermediate (2) and its subsequent reaction with phenols/amino acid esters in dry THF in the presence of triethylamine at 40-45°C. The structures of newly synthesized compounds were characterized by spectral and elemental analysis. The title compounds were evaluated for their in-vitro antioxidant properties.     

Synthesis, antihypertensive activity, and 3D-QSAR studies of some new p-hydroxybenzohydrazide derivatives

p-Hydroxybenzohydrazide 2 on treatment with aromatic/aliphatic aldehyde followed by cyclization with carbon disulphide afforded compounds 4a-4n. Also, compound 2 by treatment of substituted isothiocyanate followed by the treatment of chloroacetic acid yields the corresponding compounds 6a-6i. All the test compounds were assayed for antihypertensive activity by non-invasive blood pressure measurement and invasive blood pressure measurement methods. The test compounds showed significant antihypertensive activity. The intact compounds were subjected to 3D-QSAR studies. The 3D-QSAR analysis was carried out by PHASE program and a statistically reliable model with good predictive power (r(2) = 0.98, q(2) = 0.74) was achieved. The 3D-QSAR plots illustrated insights into the structure-activity relationship of these compounds which may aid in the design of potent p-hydroxybenzohydrazide derivatives as antihypertensive agents.     

苯并噁嗪利福霉素衍生物的合成及其抗菌活性初探

目的 设计合成苯并噁嗪利福霉素衍生物，并研究其抗菌活性。方法 以利福霉素S为原料合成目标化合物，并测定其抗菌活性。结果 初步的抗菌活性研究表明：合成的新化合物均有抗菌作用，但其抗菌活性低于对照品。结论 3′-苯并噁嗪酚利福霉素的3′位酚羟基醚化对抗菌活性有影响。     

Synthesis and antioxidant evaluation of some new 3-substituted coumarins

3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2-aminothiazole derivative 3 via bromination of 1 to afford acetylbromide 2 followed by treatment with thiourea or via Biginelli reaction of 1. Treatment of 3 with 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-methyl-4H-benzo[d][1,3]oxazin-4-one, furo[3,4-b]pyrazine-5,7-dione or 2-methyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d][1,3]oxazin-4-one afforded diazine derivatives 4-7. Also, pyridopyrimidine 8 was obtained via a one pot reaction of 6-aminothiouracil, p-chlorobenzaldehyde and 3-acetylcoumarin. Moreover, refluxing of 6-aminothiouracil with one equivalent amount of 2 afforded the thiazolopyrimidine 9, while the pyrrolothiazolopyrimidine 10 was revealed when two equivalent amounts of 2 was used. Furthermore, treatment of enamine 11 with 2-aminobenzothiazole or 6-aminothiouracil afforded the pyrimidine derivatives 12 and 13, respectively. Transamination of enamine 11 with m-anisidine followed by cyclization of the resulting enaminone 14 gave the desired quinoline 15. Also, treatment of 11 with thiophenol in dioxane gave the mercapto derivative 16. Moreover, coupling of 11 with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl-diazonium chloride, followed by complete cyclization of the resulting product afforded the pyridopyrazolothiazine 19 via the intermediate 18. Furthermore, the pyrazolopyrimidine 20 was revealed via a one pot condensation of 11, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and ammonium acetate. The thiadiazine derivatives 21-23 were obtained via treatment of 2 with the corresponding o-aminothiols. Desulphonation of 23 afforded the pyrazolotriazine 24. Finally, reaction of 2 with 2-hydroxybenzaldehyde gave benzofuran derivative 25. Representative compounds of the synthesized products were evaluated as antioxidant agents.     

Synthesis,characterization and anticoagulant activity of chitosan derivatives

Chitosan derivatives are reported as anticoagulants in the literature. This work was undertaken to develop novel chitosan derivatives as anticoagulants. The sulfonated derivatives of chitosan were formed by the reaction of chitosan derivatives with chlorosulfonic acid in N,N-dimethylformamide. The structures of these derivatives were established by FTIR and ¹H NMR spectra. The prepared derivatives were evaluated for their in vivo anticoagulant effects by the tail bleeding method in Wistar rats utilizing nicoumalone as a standard drug. The results revealed that the sulfonation of the chitosan increases its anticoagulant activity. The developed compounds exhibited faster onset of action and potency than nicoumalone after one hour of the drug administration. The sulphated N-alkyl derivatives of chitosan were more potent anticoagulants than sulfated quaternary derivatives/sulfated chitosan. It is also suggested to develop analogs of Ethyl chitosan sulfate (4b) and Benzyl chitosan sulfate (4c), which may provide some more fruitful anticoagulants having faster onset of action as well as longer duration of action and possessing a balanced hydrophilic/lipophilic character.     

Synthesis and antioxidant activity of new 1,2,4-triazole derivatives

A series of new derivatives of 1,2,4-triazoles have been synthesized and their antioxidant properties have been studied. It was established that the obtained compounds exhibit a stabilizing effect on cell membranes and demonstrate antioxidant activity with respect to erythrocytes under oxidative stress conditions.     

含有取代吲哚满二酮-1-乙基的加替沙星衍生物的合成与抗结核作用研究

目的寻找具有优秀活性的喹诺酮类抗结核药物。方法设计合成脂溶性更大的含有取代吲哚满二酮-1-乙基的加替沙星衍生物,测定其体外抗分枝杆菌活性。结果共合成了14个新化合物,其结构经1H-NMR、MS和HRMS确证。目标物普遍具有良好的抗分枝杆菌活性(MIC为1.56~6.25μg/mL),但均弱于其母药加替沙星。其中,化合物3h对草分枝杆菌CMCC93201和耻垢分枝杆菌CMCC93202的活性分别是利福平的4倍和2倍。结论脂溶性并非决定喹诺酮类化合物抗分枝杆菌活性的唯一因素。     

Synthesis and anti-microbial activity evaluation of some new 1-benzoyl-isothiosemicarbazides

The synthesis of some aroylisothiosemicarbazides was accomplished and their biological activity against bacteria, fungi, and mycobacteria was investigated. Different synthetic pathways were followed according to the kind of substituents that were introduced on both the aroyl ring and the sulfur atom. Anti-bacterial activity was measured against Staphylococcus aureus, S. epidermidis, Streptococcus agalactiae and S. faecalis, Escherichia coli, and Salmonella typhi, while antifungal activity was evaluated against C. albicans. Two species, Mycobacterium tuberculosis H37RV and Mycobacterium avium ATCC19421, were employed to evaluate antimycobacterial activity.     

多羟基(口山)酮及其衍生物的合成及抗氧化活性

目的合成多羟基(口山)酮及其脂肪胺基烷基衍生物,研究其抗氧化活性和构效关系.方法以邻甲氧基苯甲酸衍生物为起始原料,经酰氯化、Friedel-Crafts酰化、环合、脱甲基化及脂肪胺基烷基取代等反应合成目标化合物.以体外抑制Cu2 诱导的低密度脂蛋白(LDL)氧化和清除二苯代苦味肼自由基(DPPH)的EC50值检测目标化合物的抗氧化活性.结果共得到11个化合物(其中3个脂肪胺基烷基衍生物为新化合物),经IR、1H-NMR等确证其结构.初步药理试验结果表明,含邻二羟基的多羟基(口山)酮具有良好的抗氧化活性.结论邻二羟基的存在与(口山)酮衍生物的抗氧化活性有密切关系;羟基的取代数量对活性没有明显影响;取代位置对活性的影响有待进一步研究.     

Synthesis and comparison of antioxidant properties of indole-based melatonin analogue indole amino Acid derivatives

Increased levels of reactive oxygen species attributed to oxidative stress have been found to be responsible for the development of some vital diseases such as cardiovascular, neurodegenerative and autoimmune diseases. Recently, it was observed that melatonin is a highly important antioxidant, and melatonin analogues are under investigation to find out improved antioxidant activity. In this study, 14 melatonin -based analogue indole amino acid and N-protected amino acid derivatives were synthesized and elucidated spectrometrically. To investigate the antioxidant activity of the synthesized compounds and to compare with melatonin, butylhydroxytoluene and vitamin E, lipid peroxidation inhibition and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activities were tested. The results indicated that the synthesized new indole amino acid derivatives have similar activities to melatonin in 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity assay but more potent activities in lipid peroxidation inhibition assay.     

Synthesis and antitumor activity of a series of lactone-opened camptothecin derivatives

A series of E-ring lactone-opened camptothecin (CPT) derivatives bearing with terminal aza-heterocyclic groups were synthesized, and their antitumor activity was evaluated both in vitro and in vivo. Hydroxyl-amide analogues with morpholin-4-yl displayed excellent antitumor activity in vitro and efficient inhibition on tumor xenograph model in nude mice. Ester-amide compounds acted less active in vitro cytotoxicity and lower inhibition activity in vivo. Substitutions at 7- and 10- positions favored the antitumor activity.