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1.
The direct one-step synthesis of 3-(O-carboxymethyl)oximes of representative C21-4-pregnen-3,20-diones is reported. The method requires the preparation of a 3-enamine derivative which, serving as an intermediate product, is readily converted to the 3-(O-carboxymethyl)oxime upon addition of one molar equivalent of O-(carboxymethyl)hydroxylamine hemihydrochloride. The reaction appears to be generally applicable for selective 3-(O-carboxymethyl)oxime formation in steroids possessing multi-carbonyl groups, thus facilitating the coupling of steroidal haptens to protein at the C-3 position of the steroid molecule for enhanced immunospecificity. In this manner, antisera to 16α-hydroxyprogesterone and 17α-hydroxy-progesterone were obtained from immunized rabbits and specificity was established by radioimmunoassay. 相似文献
2.
Salakatte Thammaiah Harini Honnaiah Vijay Kumar Javarappa Rangaswamy Nagaraja Naik 《Russian Journal of Bioorganic Chemistry》2017,43(2):186-196
The synthesis of novel thiazole-based piperidinone oximes and screening of their antioxidant and antimicrobial activity are described. The obtained results revealed that the electronic effects of active substituents at C-4 terminals of phenyl rings on either side of piperidinone skeleton, as well as at 2-hydrazinyl thiazole, played a major role in development of antioxidant and antimicrobial activity. Antioxidant activity seems to be based also on radical dissipating ability of the thiazole ring. The nucleophilic character of sulfur in thiazole and lipophilic nature of piperidinone skeleton substantially influenced the observed antimicrobial activity of thiazole-based piperidinone oximes. Among the synthesized compounds, 2,6-bis(4-hydroxy-3-methoxyphenyl)-1-methylpiperidin-4-one O-(2-(2-(4-hydroxy-3-methoxybenzylidene)hydrazinyl)thiazol-4-yl) oxime exhibited excellent antioxidant activity whereas compound 2,6-bis(4-chloro phenyl)-1-methylpiperidin-4-one O-(2-(2-(4-nitrobenzylidene)hydrazinyl)thiazol-4-yl)oxime emerged as an outstanding antimicrobial agent. 相似文献
3.
Emami S Kebriaeezadeh A Ahangar N Khorasani R 《Bioorganic & medicinal chemistry letters》2011,21(2):655-659
As a continuation of our efforts to develop the azolylchromanone derivatives as potential anticonvulsant agents, we explored (Z)- and (E)-oxime ether derivatives of imidazolylchromanones bearing different lipophilic O-benzyl groups and tested their anticonvulsant activities in PTZ-kindling model of epilepsy. O-(2,4-Dichlorobenzyl) oximes 8a, 16a and 20a were significantly effective in delaying the onset of the PTZ-evoked seizures at the dose of 30 mg/kg in kindled animals. The most effective compounds in delaying seizures were 7-chlorochromanone-O-(2,4-dichlorobenzyl) oximes 8a and 20a. SAR studies showed that introduction of a chlorine atom to the 7-position and/or a methyl group to the 2-position of the chroman ring resulted in an improvement of anti-seizure efficacy in O-(2,4-dichlorobenzyl) oxime series. 相似文献
4.
Apigenin, a member of the flavone subclass of flavonoids, has long been considered to have various biological activities. Its glucosides, in particular, have been reported to have higher water solubility, increased chemical stability, and enhanced biological activities. Here, the synthesis of apigenin glucosides by the in vitro glucosylation reaction was successfully performed using a UDP-glucosyltransferase YjiC, from Bacillus licheniformis DSM 13. The glucosylation has been confirmed at the phenolic groups of C-4′ and C-7 positions ensuing apigenin 4′-O-glucoside, apigenin 7-O-glucoside and apigenin 4′,7-O-diglucoside as the products leaving the C-5 position unglucosylated. The position of glucosylation and the chemical structures of glucosides were elucidated by liquid chromatography/mass spectroscopy and nuclear magnetic resonance spectroscopy. The parameters such as pH, UDP glucose concentration and time of incubation were also analyzed during this study. 相似文献
5.
Rolf Andersson Olle Larm Elisabeth Scholander Olof Theander 《Carbohydrate research》1980,78(2):257-265
Sucrose and (1) were oxidised with bromine in aqueous solution at pH 7 and room temperature. The resulting keto derivatives were converted into their more-stable O-methyloximes, which were characterised by spectroscopic and chromatographic methods. Oxidation of 1 occurred at C-3 and C-5, with a preference for C-5. In the sucrose derivatives isolated after oxidation, those having a keto group in the glucopyranosyl moiety preponderated. The axial fructofuranosyl aglycon protects position 3 in the glucopyranosyl group and oxidation occurs only at C-2 and C-4. Small amounts of sucrose oxidised at C-3 in the fructofuranosyl moiety were also found. 相似文献
6.
Olle Larm Kjell Larsson Elisabeth Scholander Bernd Meyer Joachim Thiem 《Carbohydrate research》1981,91(1):13-20
Dextran T 10, elaborated by Leuconostoc mesenteroides NRRL B-512, was oxidised with aqueous bromine at pH 7.0. The resulting oxodextran and its methoximated derivative were analysed by 13C-n.m.r. spectroscopy. The total amount of keto groups and their positions were established. Assignments of the 13C signals were made by referring to spectra of the corresponding methyl glucosiduloses and an oxodextran having most of the carbonyl groups at position 3 of the glycopyranosyl residues. In accordance with the mechanism for bromine oxidation of mono- and di-saccharides, the glucopyranosyl residues of dextran were oxidised mainly at C-2 and C-4. Over-oxidation resulted in a small proportion of acidic, ring-cleavage products. 相似文献
7.
《Bioorganic & medicinal chemistry letters》2014,24(18):4424-4427
O-Alkylated quercetin analogs were synthesized and their anticancer activities were assessed by a high-throughout screening (HTS) method. The structure–activity relationships (SAR) showed that introduction of long alkyl chain such as propyl group at the C-3 OH position or short alkyl chain such as ethyl group at the C-4′ OH position were very important for keeping inhibitory activities against the 16 cancer cell lines. Furthermore, when the two n-butyl groups were introduced into the C-3, C-7 or C-4′, C-7 positions, the anticancer activity was enhanced. 相似文献
8.
Kosei Yamauchi Akari Fujieda Tohru Mitsunaga 《Bioorganic & medicinal chemistry letters》2018,28(14):2518-2522
In our previous study, the isolation of ugonin J, K, and L, which are luteolin derivatives, from the roots of Helminthostachys zeylanica and their identification as potent melanogenesis inhibitors, was described. The structure activity relationship (SAR) investigation in that study revealed that the catechol moiety in the B-ring of the flavone skeleton of ugonin K was important for its melanogenesis inhibitory activity, and the presence of the low polarity substituents at the C-7 position enhanced this activity. In order to further investigate the SAR of the C-7-substituent in the luteolin derivatives, different groups were selectively introduced at the C-7 position of luteolin after borax protection of the catechol hydroxyl group and the C-5 hydroxyl group. NMR and MS analysis of the borax protected derivatives revealed that the borax protects not only hydroxyl groups of catechol on the B ring but also the 5-hydroxyl group on the A ring. Eight luteolin derivatives were synthesized and evaluated for melanogenesis inhibitory effect in B16 melanoma cells. Two bulky groups and six alkoxyl groups were introduced at the C-7 position. The resulting luteolin derivatives showed improved melanogenesis and cell proliferation inhibitory activities. From among these derivatives, 7-O-hexylluteolin (7) showed the highest activity and inhibited the melanogenesis to 14% at 6.25?μM. The present study also revealed that the length of the carbon chain rather than the bulky substituent was more important for the melanogenesis inhibitory activity. 相似文献
9.
Ming-Daw Tsai Janet Weaver Heinz G. Floss Eric E. Conn Richard K. Creveling Mendel Mazelis 《Archives of biochemistry and biophysics》1978,190(2):553-559
The stereochemistry of the replacement of the SH-group of cysteine by CN catalyzed by β-cyanoalanine synthetase was studied using cysteine stereospecifically tritiated at C-3. Analysis of the resulting β-cyanoalanine by conversion into fumarate via aspartate and malate showed that the reaction had occurred with retention of configuration at C-3. Using cystine stereospecifically labeled at C-3 with tritium or with tritium and deuterium, it was found that the α,β-elimination reaction catalyzed by S-alkylcysteine lyase involves stereo-specific replacement of the β-substituent of the substrate by a hydrogen derived from the solvent, D2O or H2O, with retention of configuration to give pyruvate containing a chiral methyl group. The results are discussed, particularly in the light of mechanistic proposals by Braunstem and co-workers. 相似文献
10.
Oxana B. Kazakova Gul’nara V. Giniyatullina Emil Yu. Yamansarov Genrikh A. Tolstikov 《Bioorganic & medicinal chemistry letters》2010,20(14):4088-4090
The synthesis of new betulin and ursolic acid derivatives and evaluation of their antiviral activity in vitro is reported. Betulin was modified at positions C-3, C-20 and C-28 to afford the derivatives with nicotinoyl-, methoxycynnamoyl-, alkyne and aminopropoxy-2-cyanoethyl-moieties. The two stage conversion of betulin to the new ursane-type triterpenoid by treatment of allobetulin with Ac2O–HClO4 is suggested. Cyanoethylation of ursonic acid oxime led to cyanoethyloximinoderivative. According to the results of antiviral screening against human papillomavirus type 11 the selectivity index for tested triterpenoids has a range from 10 to 35 with no cellular cytotoxicite, the most remarkable activity was found for 3β,28-di-O-nicotinoylbetulin. 3β,28-Dihydroxy-29-norlup-20(30)-yne was also active against HCV replicon (EC50 1.32; EC90 16.82; IC50 12.41; IC90 >20; SI50 9.4; SI90 >1.19). 28-O-Methoxycynnamoylbetulin was active against influenza type A virus (H1N1) (ЕС50 2; IC50 >200; SI >100). 相似文献
11.
《Bioorganic & medicinal chemistry letters》2014,24(19):4743-4748
The search of proficient oximes as reactivators of irreversibly inhibited-AChE by organophosphate poisoning necessitates an appropriate assessment of their physicochemical properties and reactivation kinetics. Therefore, herein acid dissociation constant; pKa, lipophilicity; log P, polar surface area, hydrogen bond donor and acceptor counts of structurally different oximes (two tertiary oximes and thirteen pyridinium aldoxime derivatives) have been evaluated. The experimentally obtained data for pKa has been comparatively analyzed by using non-linear regression. Further the tested oximes were screened through in vitro reactivation kinetics against paraoxon-inhibited AChE. The pKa values of all the examined oximes were within the range of 7.50–9.53. pKa values of uncharged and mono-pyridinium oximes were in good correlation with their reactivation potency. The high negative log P values of pyridinium oxime reactivators indicate their high hydrophilic character; hence oximes with improved lipophilicity should be designed for the development of novel and more potent antidotes. Propane and butane linked oximes were superior reactivators than xylene linked bis-oxime reactivators. It is concluded from the present study that pKa value is not only ruled by the position of oximino functionality in the pyridinium ring, but also by the position of linker. Although, pyridinium oximes are proved to be better reactivators but their lipophilicity has to be improved. 相似文献
12.
Paramasivam Parthiban Paramasivam Rathika Venkatachalam Ramkumar Se Mo Son Yeon Tae Jeong 《Bioorganic & medicinal chemistry letters》2010,20(5):1642-1647
Libraries of 1-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 1–14/15–28/29–42 and 7-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 43–48/49–54/55–60 were synthesized and their stereochemistry was established by 1D/2D NMR spectral and single crystal XRD studies. All the synthesized oximes and oxime ethers were screened for their in vitro antimicrobial activity against a panel of pathogenic bacteria (Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa) and fungi (Candida albicans, Candida parapsilosis, Aspergillus niger and Cryptococcus neoformans) using Gentamicin and Fluconazole as standards, respectively. From the SAR profile, the lead molecules were identified. 相似文献
13.
Wagner S Kufleitner J Zensi A Dadparvar M Wien S Bungert J Vogel T Worek F Kreuter J von Briesen H 《PloS one》2010,5(12):e14213
Background
Due to the use of organophosphates (OP) as pesticides and the availability of OP-type nerve agents, an effective medical treatment for OP poisonings is still a challenging problem. The acute toxicity of an OP poisoning is mainly due to the inhibition of acetylcholinesterase (AChE) in the peripheral and central nervous systems (CNS). This results in an increase in the synaptic concentration of the neurotransmitter acetylcholine, overstimulation of cholinergic receptors and disorder of numerous body functions up to death. The standard treatment of OP poisoning includes a combination of a muscarinic antagonist and an AChE reactivator (oxime). However, these oximes can not cross the blood-brain barrier (BBB) sufficiently. Therefore, new strategies are needed to transport oximes over the BBB.Methodology/Principal Findings
In this study, we combined different oximes (obidoxime dichloride and two different HI 6 salts, HI 6 dichloride monohydrate and HI 6 dimethanesulfonate) with human serum albumin nanoparticles and could show an oxime transport over an in vitro BBB model. In general, the nanoparticulate transported oximes achieved a better reactivation of OP-inhibited AChE than free oximes.Conclusions/Significance
With these nanoparticles, for the first time, a tool exists that could enable a transport of oximes over the BBB. This is very important for survival after severe OP intoxication. Therefore, these nanoparticulate formulations are promising formulations for the treatment of the peripheral and the CNS after OP poisoning. 相似文献14.
The reactions of pea diamine oxidase (PSAO) and 2-phenylethylamine oxidase from Arthrobacter globiformis (AGAO) with pyridine-derived oximes were studied. Pyridine carbaldoximes and alkyl pyridyl ketoximes act as strong non-competitive inhibitors of the enzymes. The inhibition constants K(i) of these compounds vary between 10(-4) and 10(-5) M, for AGAO and some of the studied oximes were found even micromolar K(i) values. The presence of pyridine moiety in the studied compounds has remarkable influence on the inhibition potency. Elementary oximes lacking the heterocyclic ring, i.e., aliphatic (acetone oxime), alicyclic (cyclohexanone oxime) and aromatic (benzaldoxime), are considerably weaker non-competitive inhibitors (K(i) similar to 10(-3) or 10(-2) M). The position of the pyridine ring substitution by -C(R)=NOH group does not play a significant role for the inhibition potency of the studied oxime compounds. If the pyridine nitrogen is quaternised (in hydroxyiminomethyl-1-methylpyridinium iodides), the compound looses its inhibitory properties. Extended length of alkyl substituents on the ketoxime group of alkyl pyridyl ketoximes increases the K(i) value. The enzyme-bound copper represents one of possible target sites for pyridine-derived oxime inhibitors. The addition of an alkyl pyridyl ketoxime or a pyridine carbaldoxime to a native PSAO sample perturbs the absorption spectrum of the enzyme (by an absorption increase in the region 300-400 nm) that is not observed in the spectrum of reacted PSAO apoenzyme. However, an additional formation of hydrogen bonds with amino acid side-chains at the active site should be considered, namely for 3- and 4-substituted pyridine derivatives. 相似文献
15.
Wang J Bourguet-Kondracki ML Longeon A Dubois J Valentin A Copp BR 《Bioorganic & medicinal chemistry letters》2011,21(4):1261-1264
The electrophilic reactivity of the bioactive marine sponge natural product halenaquinone has been investigated by reaction with the biomimetic nucleophiles N-acetyl-l-cysteine and Nα-acetyl-l-lysine. While cysteine reacted at the vacant quinone positions C-14 and C-15, lysine was found to react preferentially at the keto-furan position C-1. A small library of analogues was prepared by reaction of halenaquinone with primary amines, and evaluated against a range of biological targets including phospholipase A2, farnesyltransferases (FTases) and Plasmodium falciparum. Geranylamine analogue 11 exhibited the most potent activity towards FTases (IC50 0.017-0.031 μM) and malaria (IC50 0.53-0.62 μM). 相似文献
16.
《Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism》1981,663(1):194-202
According to Ohba et al. (Ohba M., Sato R., Yoshida Y., Nishino T. and Katsuki H. (1978) Biochem. Biophys. Res. Commun. 85, 21–27), yeast microsomes catalyze the removal of three methyl groups attached to the C-4 and C-14 positions of [1,7,15,22,26,30-14C]lanosterol (4,4,14α-trimethyl-5α-cholesta-8, 24-dien-3β-ol) in the presence of NADPH, NAD+ and molecular oxygen, concomitant with the liberation of 14CO2 derived from C-30 (one of the two methyl groups at the C-4 position). In this process the methyl group at the C-14 position is first removed in a cyanide-insensitive reaction and then the two methyl groups at the C-4 position are removed by a cyanide-sensitive enzyme system. In this study it was found that the 14CO2 formation from the 14C-labeled lanosterol was inhibited by antibodies to yeast cytochrome b5 and by palmitoyl-CoA, a substrate of the cytochrome b5-containing fatty acyl-CoA desaturase system of yeast microsomes. However, neither the antibodies nor palmitoyl-CoA inhibited the conversion of lanosterol to 4,4-dimethyl zymosterol (4,4-dimethyl-5α-cholesta-8,24-dien-3β-ol). It is concluded that cytochrome b5 and a cyanide-sensitive enzyme are involved in the 4-demethylation of 4,4-dimethylzymosterol, but not the 14α-demethylation of lanosterol, by yeast microsomes. It is suggested that a cyanide-sensitive enzyme acts as the terminal 4-demethylase and cytochrome b5 transfers reducing equivalents from NADPH to the terminal enzyme, as in the case of fatty acyl-CoA desaturation. The cyanide sensitivity of the 4-demethylation was, however, much greater than that of the desaturation. 相似文献
17.
Tomoaki Miura Satomi Natsume Kenichi Kanemoto Eiki Shitara Hideki Fushimi Takuji Yoshida Keiichi Ajito 《Bioorganic & medicinal chemistry》2010,18(7):2735-2747
The design and synthesis of 16-membered azalides modified at the C-15 and 4″ positions are described. The compounds we report here are characterized by an arylpropenyl group attached to the C-15 position of macrolactone and a carbamoyl group at the C-4″ position in a neutral sugar. Introduction of alkylcarbamoyl groups to the C-4″ position was regioselectively achieved by unique and convenient methods via acyl migration. As a result of optimization at the C-3 and 15 positions, several compounds were found to have potent activity against mef- and erm-resistant bacterial strains. These results suggest that 16-membered azalides could be promising compounds as clinical candidates. 相似文献
18.
The primary acid product of DPNH 总被引:1,自引:0,他引:1
N J Oppenheimer 《Biochemical and biophysical research communications》1973,50(3):683-690
Analysis of the proton magnetic resonance spectra obtained at 220 MHz confirms the axial conformation of the C-6 hydroxyl in the model primary acid product 1-n-(2,6-dichlorobenzyl)-6-hydroxy-1,4,5,6-tetrahydronicotinamide. In the primary acid product of DPNH however the reaction occurs stereospecifically with the substitution at the C-6 position equatorial and on the B-side of the pyridine ring and the C-4A proton axial. A cyclic structure α,O2′-6B cyclotetrahydronicotinamide is proposed for the primary acid product of DPNH, formed by epimerization of βDPNH to the α configuration followed by protonation at C-5 and subsequent attack of the ribose C-2′-OH on the C-6 position forming a new five membered ring. 相似文献
19.
R W Furlanetto M Mochizuki E T Kaiser 《Biochemical and biophysical research communications》1974,58(1):192-196
-α-chloroacetophenone oxime has been found to inactivate papain rapidly at pH 7 and 25.0O in a 1:1 stoichiometric fashion as measured by rate assays with -nitrophenyl -benzyloxycarbonylglycinate and sulfhydryl group titrations with 5,5′-dithiobis-(2-nitrobenzoic acid). By the use of a 14C label in the halomethyl function a similar stoichiometric reaction with papain could be demonstrated for -α-bromoacetophenone oxime despite the rapidity of the competitive nonenzymatic solvolysis of the latter compound under the conditions employed. These results indicate that a new class of reactive modifying agents, α-haloalkyl oximes, can be used for the selective alkylation of catalytically essential functional groups in enzyme active sites. 相似文献
20.
《Chemistry and physics of lipids》1986,40(1):57-69
Evidence is presented which shows that in the preparation of radiolabeled cholesterol and other Δ5-sterols via the technique of tritium exchange-labeling of keto steroids and their subsequent conversion to sterol, 3H is introduced primarily into positions 2 and 6 ([2,2,4.6-3H]-cholest-5-en-3β-ol) rather than exclusively at 2 and 4 as the literature claims. The stoppered-vial method using sodium methoxide versus column using basic alumina was the preferred method of labeling. It gave labeled keto steroids of reproducible specific activity indicative of the number of exchangeable protons. Because the initial oxidation step is critical to the preparation of 3H-sterols especially on the small scale, four common oxidants: pyridinium chlorochromate (Corey reagent), silver carbonate on Celite (Fetizon reagent), aluminum isopropoxide (modified Oppenhauer reagent) and chromic acid (Jones reagent) were compared using as starting materials, cholesterol, cholest-8-en-3β-ol, ergosterol, 24-methylenecholesterol, 24(25)-dihydrolanosterol, lanosterol, sitosterol and stigmasterol. The effectiveness of the oxidant was markedly influenced by the molecular features of the sterol. 相似文献