Synthesis and characterization of 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids with a branched-acyl chain

We previously reported the chemical synthesis of a series of novel monoacylated vitamin C derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids (6-Acyl-AA-2G) possessing a straight-acyl chain of varying length from C(4) to C(18), as effective skin antioxidants. In this paper, we describe branched type of 6-Acyl-AA-2G derivatives (6-bAcyl-AA-2G) synthesized by use of a 2-branched-chain fatty acid anhydride as an acyl donor. The stability of 6-bAcyl-AA-2G in neutral solution was much higher than that of 6-Acyl-AA-2G, while they were susceptible to enzymatic hydrolysis for exerting vitamin C effect. These branched derivatives as well as 6-Acyl-AA-2G increased the radical scavenging activity against 1, 1-diphenyl-2-picrylhydrazyl and the lipophilicity in octanol/water-partitioning systems with increasing length of their acyl group. In addition, the 6-bAcyl-AA-2G derivative with an acyl chain of C(12), 6-bDode-AA-2G had the excellent solubility to various solvents, suggesting easy handling in cosmetic use. These characteristics of 6-bAcyl-AA-2G may be available for skin care application as an effective antioxidant.     

Swarnalin and cis-swarnalin, two new tetrahydrofuran derivatives with free radical scavenging activity, from the aerial parts of Cuscuta reflexa

The reversed-phase HPLC analysis of a methanol extract of the aerial parts of Cuscuta reflexa afforded a non-separable mixture (55 : 45) of two novel tetrahydrofuran derivatives, named swarnalin (1) and cis-swarnalin (2), and a known coumarin, 5,6,7-trimethoxycoumarin (3). The structures of the compounds were elucidated unequivocally by UV, HRFABMS and a series of 1D and 2D NMR analyses. The mixture of 1 and 2 showed significant free radical scavenging activity in the DPPH assay and the RC50 value was found to be 3.80 x 10(-4) mg mL(-1) for the mixture, compared to 2.88 x 10(-5) mg mL(-1) for the positive control, quercetin.     

Determination of in vitro antioxidant and radical scavenging activities of propofol

Propofol (2,6-diisopropylphenol) is a hypnotic intravenous agent with in vivo antioxidant properties. This study was undertaken to examine the in vitro antioxidant activity of propofol using different antioxidant tests including by 1,1-diphenyl-2-picryl-hydrazil (DPPH.) radical scavenging, metal chelating, hydrogen peroxide scavenging, superoxide anion radical scavenging, reducing power and total antioxidant activities. At the concentrations of 25, 50, and 75 microg/ml, propofol exhibited 97.7, 98.6 and 100% inhibition on peroxidation of linoleic acid emulsion, respectively. On the other hand, at the 75 microg/ml concentration of standard antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and alpha-tocopherol exhibited 88.7, 94.5, and 70.4% inhibition on peroxidation of linoleic acid emulsion, respectively. In addition, at same concentrations, propofol was shown that it had effective reducing power, DPPH. free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging and metal chelating activities. These various antioxidant activities were compared to standard antioxidants such as BHA, BHT and alpha-tocopherol. These results indicate that propofol prevents lipid peroxidation and radicalic chain reactions. At the same time, propofol revealed more effective antioxidant capacity than BHA, BHT and alpha-tocopherol.     

A novel series of thromboxane A2 synthetase inhibitors with free radical scavenging and anti-peroxidative activities

A novel series of indoline derivatives with imidazole and carboxyl moieties were synthesized and evaluated for their thromboxane A2 (TXA2) synthetase inhibiting, radical scavenging and anti-peroxidative activities. Among the compounds synthesized, 3-[5-substituted-3-[2-(imidazol-1-yl)ethyl]indolin-1-yl]propionic acids showed free radical scavenging activity and inhibitory effects on lipid-peroxidation of rat brain homogenate and on arachidonate-induced TXA2-dependent aggregation of rabbit platelets. The anti-platelet and anti-peroxidative activities were related to the lipophilicity of the 5-substituent. The 5-hexyloxy derivative (13) showed about 35-fold higher inhibitory activity on TXA2 synthesis than that of ozagrel and about 100-fold higher activity on lipid peroxidation than that of alpha-tocopherol. Compound 13 showed in vivo anti-thrombotic effect in mice and ex vivo anti-peroxidative activity in rats.     

The determination of thiols with diphenylpicrylhydrazyl as a spectrophotometric reagent

Diphenylpicrylhydrazyl (DPPH), a stable, intensely purple free radical, is used as a reagent in the quantitative determination of various aromatic and aliphatic thiols by indirect spectrophotometric analysis. Plots of degree of reaction vs. time show that thiophenol and its derivatives react more quickly than aliphatic thiols with DPPH. Calibration plots are linear over the concentration range 0.05-3.00 x 10(-5)M thiol. The average relative error is in the range 1-2% and the absolute standard deviations range up to 0.50 x 10(-6)M.     

Antioxidant activities of extracts and metabolites isolated from the fungus Antrodia cinnamomea

Three different solvent partitions (n-hexane, ethyl acetate [EtOAc] and n-BuOH) of the culture broth from Antrodia cinnamomea were assayed with two different radical scavenging methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and superoxide radical scavenging (SOD) assay. The EtOAc layer exhibited the best antioxidant activity. Two major antioxidant metabolites were isolated from the active EtOAc layer. The antioxidant activities of compounds 1-6 were further evaluated by DPPH, SOD and trolox equivalent antioxidant capacity (TEAC) assays. Compounds 3 and 5 showed stronger free radical scavenging than the reference BHA, ED???=?1.36 and 34.24 μM. Compound 5 displayed moderate SOD activity (ED???=?310.0?μM), and its antioxidant capacity of TEAC value was 2.2 mM trolox equivalency.     

Synthesis,antioxidant, and antimicrobial activity of 3-(1H-indole-3-carbonyl)-2H-chromen-2-ones

A simple and convenient method for the one-pot synthesis of 3-(1H-indole-3-carbonyl)-2H-chromen-2-one derivatives from the reaction of 3-cyanoacetyl indole and salicylaldehyde in the presence of Na₂CO₃ in water: methanol (1:1) is described. Wider substrate scope, high yields, operational simplicity, and simple purification process make the protocol highly applicable in the synthesis of 3-(1H-indole-3-carbonyl)-2H-chromen-2-ones. For the first time, in vitro antioxidant and antimicrobial activity was studied. Compounds 5e , 7a , and 7b exhibits good radical scavenging ability against DPPH free radical. Compounds 7b , 5f , and 5g possess lower EC₅₀ values than the Standards AA and BHA and thus proving their high reducing power. Compounds 5d and 5f show good antibacterial activity against gram-positive bacteria (MRSA) while compounds 5c , 7a , and 7b exhibits good antibacterial activity against Bacillus sp. Compounds 5b and 5e show good antibacterial activity against gram negative bacterial strains (Escherichia coli, Klebsiella pneumoniae) and compounds 5g and 5h exhibits good antifungal activity against Candida albicans.     

Key role of chemical hardness to compare 2,2-diphenyl-1-picrylhydrazyl radical scavenging power of flavone and flavonol O-glycoside and C-glycoside derivatives

The antioxidant activities of flavonoids and their glycosides were measured with the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH radical, DPPH(·)) scavenging method. The results show that free hydroxyl flavonoids are not necessarily more active than O-glycoside. Quercetin and kaempferol showed higher activity than apigenin. The C- and O-glycosides of flavonoids generally showed higher radical scavenging activity than aglycones; however, kaempferol C3-O-glycoside (astragalin) showed higher activity than kaempferol. In the radical scavenging activity of flavonoids, it was expected that OH substitutions at C3 and C5 and catechol substitution at C2 of B ring and intramolecular hydrogen bonding between OH at C5 and ketone at C3 would increase the activity; however, the reasons have yet to be clarified. We here show that the radical scavenging activities of flavonoids are controlled by their absolute hardness (η) and absolute electronegativity (χ) as a electronic state. Kaempferol and quercetin provide high radical scavenging activity since (i) OH substitutions at C3 and C5 strikingly decrease η of flavones, (ii) OH substitutions at C3 and C7 decrease χ and η of flavones, and (iii) phenol or o-catechol substitution at C2 of B ring decrease χ of flavones. The coordinate r(χ,?η) as the electron state must be small to increase the radical scavenging activity of flavonoids. The results show that chemically soft kaempferol and quercetin have higher DPPH radical scavenging activity than chemically hard genistein and daidzein.     

ESR study on the antioxidant activity of TAK-218 in biological model membranes

TAK-218 has a 2,3-dihydrobenzofuran-5-amine (coumaran) structure which resembles alpha-tocopherol, and is a promising candidate as an agent for central nervous system (CNS) trauma and ischemia. The radical scavenging activity of TAK-218 was studied using electron spin resonance (ESR) spectroscopy. TAK-218 exhibited a more potent scavenging activity towards the hydroxyl radical than did the well-known hydroxyl radical scavengers, mannitol and dimethylsulfoxide. Towards the superoxide radical, TAK-218 showed equal potency to glutathione. TAK-218 reacted rapidly with stable radicals, such as galvinoxyl and 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH), and gave the quinone as a two-electron oxidized product in analogy with alpha-tocopherol. To exhibit an excellent antioxidative activity in living systems, the compounds should not only have the intrinsic radical scavenging activity but also good distribution in the biological lipid-bilayer membrane. To examine the antioxidant activity of TAK-218, the inhibition of lipid peroxidation by alpha-tocopherol and TAK-218 in liposomal membranes was studied using an ESR spin-label technique. Both alpha-tocopherol and TAK-218 completely inhibited lipid peroxidation by radicals generated in an aqueous layer using a water-soluble radical initiator, 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH). At a high incubation temperature (45 degrees C), alpha-tocopherol scavenged radicals more effectively than TAK-218 on the surface of the membrane, while TAK-218 scavenged radicals more effectively in the interior of the membrane. The difference between TAK-218 and alpha-tocopherol for radical scavenging in the membrane system derives from the different distribution pattern of these compounds. TAK-218 can penetrate the membrane freely and can scavenge the radical in the membrane interior. Furthermore, TAK-218 was shown to inhibit lipid peroxidation initiated by a lipid soluble radical initiator, 2,2'-azobis-(2,4-dimethylvaleronitrile) (AMVN), in a membrane more effectively than alpha-tocopherol.     

Syntheses,characterization, in vitro antiglycation and DPPH radical scavenging activities of isatin salicylhydrazidehydrazone and its Mn (II), Co (II), Ni (II), Cu (II), and Zn (II) metal complexes

2-Hydroxy salicylhydrazide isatin hydrazone (L) and its Mn (II), Co (II), Ni (II), Cu (II), and Zn (II), metal complexes were synthesized. ¹H NMR, UV–Vis, IR spectroscopy and elemental (CHN/S) analysis techniques were applied for characterization. TG/DTA techniques revealed that all the synthetic compounds are thermally stable up to 300 °C. They were found non-electrolytes in nature. Furthermore, all these complexes were evaluated for antiglycation and DPPH radical scavenging activities. They showed varying degree of activity with IC₅₀ values between 168.23 and 269.0 μM in antiglycation and 29.63–57.71 μM in DPPH radical scavenging activity. Mn (II), Co (II), Ni (II), Cu (II), and Zn (II), metal complexes showed good antiglycation as well as DPPH radical scavenging activity. The IC₅₀ values for antiglycation activity are 168.23 ± 2.37, 234.27 ± 4.33, 257.1 ± 6.43, 267.7 ± 8.43, 269.0 ± 8.56 Ni for Co, Zn, Mn, Cu, and Ni complexes, respectively, while IC₅₀ value were found to be 29.63 ± 2.76, 31.13 ± 1.41, 35.16 ± 2.45, 43.53 ± 3.12, 57.71 ± 2.61 μM for Cu, Zn, Mn, Co and Ni complexes, respectively, for DPPH radical scavenging activity. These synthesized metal complexes were found to be better active than standards Rutin (IC₅₀ = 294.46 μM) for anti-glycation, and tert-butyl-4-hydroxyanisole (IC₅₀ = 44.7 μM) for DPPH radical scavenging activity.     

Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives embedded with benzimidazole moiety as potent antioxidants

Fourteen novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives bearing benzimidazole moiety ( 7a-n ) have been synthesized using the one-pot nitro reductive cyclization method. All the synthesized compounds were confirmed by ¹H nuclear magnetic resonance (¹H NMR), ¹³C NMR, fourier-transform infrared (FT-IR), mass spectrum, and elemental analyses. All the title compounds were subjected to in vitro antioxidant activity. The free radical scavenging activity of the compounds was examined using DPPH, nitric oxide, and superoxide radical scavenging methods. The results demonstrated that compound 3-(2-(3,4-dimethoxyphenyl)-1-propyl-1H-benzo[d]imidazol-5-yl)-6-4-tolyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine ( 7c ) was potent in scavenging both DPPH and nitric oxide radical with IC₅₀ values of 13.57 and 18.55 μg/ml when compared to the standard with IC₅₀ values of 23.75 and 23.14 μg/ml, respectively, which was due to the presence of electron-donating groups. The activity was found to decline when electron-donating groups were replaced by electron-withdrawing groups. Moderate scavenging activity was observed for the superoxide radical. Structure activity relationship and physiochemical properties were studied for all the derivatives.     

Synthesis, anti-bacterial and anti-oxidant properties of thiadiazaphosphol-2-ones

4-Amino-5-phenyl-4H-1,2,4-triazole-3-thiol (1) underwent facile condensation with various phosphorus dichlorides (2a-j) in the presence of triethylamine in dry tetrahydrofuran at 60-65 degrees C and afforded corresponding thiadiazaphosphol-2-ones (3a-j). Their chemical structures were characterized using IR, (1)H-, (13)C-, (31)P-NMR and Mass spectral studies. All the title compounds were screened for antioxidant properties by radical scavenging methods such as 1,1-diphenyl-2-picryl hydrazyl (DPPH), hydroxyl and lipid peroxidation. They exhibited potent in vitro antioxidant activity dose dependently. Their bioassay showed them to possess significant antibacterial activity.     

Comparison of the simple cyclic voltammetry (CV) and DPPH assays for the determination of antioxidant capacity of active principles

Antioxidant activity of a number of small (low molecular weight) natural compounds found in spices, condiments or drugs (gallic acid, sesamol, eugenol, thymol, carvacrol, vanillin, salicylaldehyde, limonene, geraniol, 4-hexylresorcinol, etc.) has been evaluated using electrochemical and DPPH? radical scavenging measurements. Structural analysis of the tested compound suggest a remarkable activity for phenol derivatives and the importance of the -R groups located on the phenolic ring in the molecule's ability to act as free radical scavenging as well as their influence in the electrochemical behavior. The voltammetric method can be used for the determination of the antioxidant capability in the same manner as the DPPH? radical scavenging because of the correlation found between oxidation potentials and anti-radical power (ARP = 1/EC??). Such electrochemical determination is fast and cheap and allows making measurements under a variety of experimental conditions. The accuracy of the electrochemical measurements is the same for all the compounds, irrespective of their scavenging activity, the opposite of what occurs in the DPPH? test.     

A new chromone, 11-hydroxy-sec-O-glucosylhamaudol from Ostericum koreanum

From the ethyl acetate fraction of the roots of Ostericum koreanum, a new chromone, 11-hydroxy-sec-O-glucosylhamaudol (1) along with the known compounds: four chromones, three coumarins, six phenolic compounds, and three quinic acids were isolated. These compounds were assessed for antioxidant activities in the DPPH radical and superoxide anion radical scavenging assay systems. Among isolates, 4-(2-hydroxy-vinyl)-benzene-1,2-diol (12) showed the most potent DPPH radical scavenging activity (IC(50)=4.80+/-0.62 mug/ml) and superoxide anion radical scavenging activity (IC(50)=11.05+/-0.83 microg/ml) in the xanthine/xanthine oxidase system. The antioxidant activities of 12 were comparable to those of quercetin and luteolin.     

Synthesis and pharmacological evaluation of new progesterone esters as 5alpha-reductase inhibitors

In this study we report the synthesis and pharmacological evaluation of four new progesterone derivatives; 17alpha-hydroxy-16beta-methylpregna-4,6-diene-3,20-dione 12, 17alpha-cyclopropylcarbonyloxy-16beta-methylpregna-4,6-diene-3,20-dione 13, 17alpha-cyclobutylcarbonyloxy-16beta-methylpregna-4,6-diene-3,20-dione 14, 17alpha-acetoxy-16beta-methylpregna-4,6-diene-3,20-dione 15 and the pregnatriene compound 17alpha-cyclobutylcarbonyloxy-16beta-methylpregna-1,4,6-triene-3,20-dione 16. The pharmacological effect of these compounds was determined in vivo as well as in vitro. The evaluation in vivo was carried out on gonadectomized male hamsters that were injected subcutaneously daily with testosterone (T) and/or finasteride, or with the novel compounds. At the end of the treatments the animals were sacrificed and the prostates were weighed. It was observed that when testosterone (T) and finasteride or compounds 12-16 were injected together, the weight of the prostate decreased significantly as compared to that of the testosterone-treated animals. The 5alpha-reductase inhibitory activity was evaluated in vitro using human prostate homogenates. These experiments showed the following IC50 values: compound 12 (alcohol at C-17) 1.2 x 10(-6) M, 13 (cyclopropyl substituent at C-17) 7.9 x 10(-10) M, 14 (cyclobutyl substituent) 3.2 x 10(-8) M, 15 (acetoxy substituent) 6.3 x 10(-11) M and 16 (cyclobutyl substituent) 3.9 x 10(-6) M. It is evident from these data that when the size of the substituent at C-17 is decreased, the 5alpha-reductase inhibitory activity increases. Apparently, in this biological model, the 5alpha-reductase inhibitory activity depends upon the steric effect of the substituent at C-17. However, the free alcohol 12 showed much lower 5alpha-reductase inhibitory activity.     

Structural determination and DPPH radical-scavenging activity of two acylated flavonoid tetraglycosides in oolong tea (Camellia sinensis)

Two major acylated flavonoid tetraglycosides were isolated from the methanol extract of oolong tea. Their structures were elucidated by spectroscopic methods as quercetin 3-O-[2(G)-(E)-coumaroyl-3(G)-O-beta-D-glucosyl-3(R)-O-beta-D-glucosylrutinoside] (1) and kaempferol 3-O-[2(G)-(E)-coumaroyl-3(G)-O-beta-D-glucosyl-3(R)-O-beta-D-glucosylrutinoside] (2). Compounds 1 and 2 exhibited scavenging activity against DPPH radical with EC(50) values of 30.5 and 487.2 microM, respectively.     

Novel N-(benzo[d]oxazol-2-yl)alkanamides; synthesis and carbonic anhydrase II inhibition studies

Carbonic anhydrase (CA II) inhibitors are very important therapeutic targets in drug design for treatment of neuropathic pain and in eradication of glaucoma, cancer, epilepsy, ulcer and obesity. In this study, some two2-substituted benzoxazoles ( 3a-j ) were developed as a new family of carbonic anhydrase II inhibitors by employing acyl thiourea chemistry via a simple and expedient protocol and evaluated for CA II inhibitor activity and radical scavenging ability. Compounds 3f and 3j were found to be the most potent inhibitors, with IC₅₀ values of 0.00564 and 0.00596 μM, respectively which are several times better than that of the standard, acetazolamide (IC₅₀ value 0.997 ± 0.0586 μM). Docking experiments were carried out against the carbonic anhydrase II crystal structure to better rationalize the inhibitory activities of these new structures. Moreover, the results of a DPPH radical scavenging assay showed that the antioxidant profile of compound 3i is superior to those of other derivatives. The results have revealed that derivatives 3f and 3j behave as CA-II inhibitors significantly better than standard and 3i has good anti-oxidation potential.     

Synthesis,characterization and antioxidant activities of highly functionalized cyclopentadienes catalyzed by ZnO-nanorod as economic and efficient heterogeneous nano catalyst

A three-component condensation was applied for the preparation of cyclopentadiene derivatives through the reaction of primary amines, alkyl propiolate and dialkyl acetylenedicarboxylate in the presence of catalytic amount of ZnO-nanorods (Zn-NR) under solvent-free conditions at 50℃. The method has proved to be synthetically green, simple, and effective with high atom economy and yield. The catalyst also revealed significant reusability. Moreover, the antioxidant activity and free radical scavenging capacity of the newly synthesized derivatives 4a, 4b, 4c, and 4d was screened using free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays and compared with hydroxytoluene (BHT) and tert-butylhydroquinone (TBHQ). These compounds do not exhibit good DPPH radical scavenging, but they have a desirable FRAP.     

Phenolic compounds in field horsetail (Equisetum arvense L.) as natural antioxidants

In this paper, the study of antioxidant activity and phenolic composition of three different extracts (EtOAc, n-BuOH and H(2)O) of field horsetail (Equisetum arvense L.) is presented. The antioxidant activity has been evaluated measuring the total reducing power (expressed by Ascorbate Equivalent Antioxidant Capacity - AEAC), inhibition of lipid peroxidation, and free radical scavenging capacity (RSC) towards 2,2-diphenyl-1-picrylhydrazyl (DPPH radical) and nitric oxide (NO), respectively. In addition, the total flavonoid content (TFC) and phenolic constituents of each extract have been determined. The results obtained show that the highest RSC regarding both DPPH and NO radicals is expressed by EtOAc extract (EC(50)=2.37 microg/mL and EC(50)=90.07 microg/mL, respectively), and the lowest by H(2)O extract (EC(50)=37.2 microg/mL and EC(50)>333.33 microg/mL, respectively). n-BuOH extract showed the highest total reducing power (AEAC=13.40 microg/mL). Differences in the phenolic composition of examined extracts are found comparing the HPLC chemical profiles. Although, isoquercitrin is the main flavonoid in both EtOAc and n-BuOH extracts, a considerable amount of di-E-caffeoyl-meso-tartaric acid was presented in the n-BuOH extract. In H(2)O extract high content of phenolic acids and low percentage of flavonoids were detected.     

A synthesis of 2-substituted 2-aminoethanol derivatives having inhibitory activity against protein kinase C.

A series of 2-aminoethanol derivatives was synthesized and their inhibitory activities against protein kinase C were investigated. Among these compounds, 2-endo-hexadecylamino-5-norbornene-2- exo-methanol (4h) and 2-endo-hexadecylamino-5-norbornene-2,3-exo-dimethanol (4i) inhibited protein kinase C at the IC50 values of 2 x 10(-5) and 1 x 10(-5) M, respectively, but not protein kinase A at a concentration of 1 x 10(-3) M. The structure-activity relationships are discussed.