Mitsunobu dehydration of N-Boc neomycin B

Reaction of hexa-N-Boc neomycin B with TPP and DIAD in toluene results in the formation of an epoxide in ring IV, not an aziridine or azetidine as previously reported.     

Trisaccharide mimetics of the aminoglycoside antibiotic neomycin

A highly convergent approach for the chemical synthesis of eight structurally related trisaccharides that contain 3 to 5 amino groups has been described. Fourier-transformation ion cyclotron resonance mass spectrometry (FT-ICR MS) has been employed to determine the dissociation constants (Kd) for the binding of the trisaccharides to a prototypical fragment of 16S ribosomal RNA. A compound that contained a 4,6-dideoxy-4-amino-beta-D-glucopyranoside moiety at C-3 displayed binding in the low micromolar range. It was found that small structural changes of the saccharides resulted in large differences in affinity. The described structure-activity relationship is expected to be valuable for the development of novel antibiotics that target rRNA.     

Spectrophotometric microdetermination of amoxicillin and neomycin with chloranil

Ampicillin trihydrate (12.5–750 μg) is determined spectrophotometrically using chloranil as π-acceptor at pH 9. The method is relatively accurate (with a recovery of 100 ± 1.0%) and precise (RSD 1.7%) and can be used successfully for capsules and ampoules.     

Determination of neomycin in animal tissues by liquid chromatography

Tissue samples are digested under hot alkaline conditions after initial conditioning at room temperature with phosphate-buffered saline. The cooled digest is deproteinated with concentrated perchloric acid. After centrifugation and pH adjustment, the clear supernatant is applied to an ion-exchange cartridge, and after the cartridge is washed, the neomycin is eluted with dilute perchloric acid. This eluate is derivatized with 9-fluorenylmethyl chloroformate prior to liquid chromatography using a wide-pore spherical silica C4 column and fluorescence detection. Recovery and repeatability are calculated from tissue extract standard calibration curves produced from the same assay. Recoveries ranged from 80 to 120% for fortifications of 0.25-1.00 mg/kg for muscle tissue and from 80 to 100% for fortifications of 0.50-10.0 mg/kg for kidney tissue. Limits of quantitation were 0.25 and 0.50 mg/kg, respectively, for muscle and kidney tissues. Limits of detection were 0.125 and 0.20 mg/kg, respectively, for muscle and kidney tissues.     

Application of isotachophoretic and conductometric methods for neomycin trisulphate determination

Determination of neomycin trisulphate (NMS) in a dosage form (Neox and Neosol) was carried out by capillary isotachophoresis (cITP) with conductometric detection. The following electrolytes: leading: 10 mmol dm⁻³ sodium acetate + 0.08 % hydroxyethylcelulose (HEC) and acetic acid to pH = 5.5, and terminating: 10 mmol dm⁻³ β-alanine were tested for isotachophoretic separation of NMS. The calibration curve was linear over the range of 10.00 mg dm⁻³ to 100.00 mg dm⁻³ with LOD = 5.69 mg dm⁻³ and LOQ = 18.96 mg dm⁻³. The results were compared to the conductometric determination of NMS with: ammonium molybdate (VI), silver nitrate (V) and Reinecke salt. Good accuracy was obtained from conductometric titration of NMS with Reinecke salt, the recoveries being as follows: 100 % (RSD = 1.99 %); 96.17 % (RSD = 2.10 %) and 95.22 % (RSD = 1.55 %) for NMS in pure form, Neosol and Neox, respectively.     

Spectrophotometric determination of amikacin,kanamycin, neomycin and tobramycin

A spectrophotometric method for determination of neomycin, kanamycin, tobramycin and amikacin is proposed, based on the Rimini test with disodium pentacyanonitrosylferrate(II) for primary and secondary aliphatic amines. The absorbance of the coloured addition product is measured. Beer's law is valid over a wide concentration range. The method is relatively fast and can be used in control of the manufacture of the antibiotics and their purity, instead of the much slower microbiological method. It is also applicable for determination of these antibiotics in formulations.     

Optimizing the quadruple-potential waveform for the pulsed amperometric detection of neomycin

Determination of neomycin is important for quality control of the pharmaceutical preparation. A quadruple-potential waveform used for pulsed amperometric detection of neomycin was investigated. The waveform cleans the electrode by application of a potential more negative than the potential limit to avoid the formation of gold oxide during applying positive potential to clean gold electrode, thus decreasing the dissolution resulting recession of the gold working electrode within gold oxide formation/reduction cycles in the triple-potential waveform. Waveform parameters were optimized to maximize the signal-to-noise ratio (S/N). The detection limit of neomycin B is lower than 0.01 microg/ml. The linearity of framycetin (plotted as peak area of neomycin B) ranges from 0.05 to 100 microg/ml with correlation coefficient 0.9998. R.S.D. (n = 60) of the peak area of neomycin B is lower than 2%. The quadruple-potential waveform shows low detection limits and long-term reproducibility.     

牛奶样品中新霉素残留量的离子色谱法测定

建立了阴离子交换色谱-脉冲安培检测分析牛奶中新霉素残留量的方法.实验采用三氯乙酸沉淀蛋白,弱阳离子交换固相萃取柱富集净化,处理牛奶样品,并考察了三氯乙酸浓度、样品过柱速度以及洗脱剂浓度等因素对牛奶中新霉素测定结果的影响.牛奶中新霉素的回收率在50.3%～76.9%范围内,基底加标工作曲线的相关系数为0.9949(n=6),线性范围为10.0～160.0ng/mL.所建立的方法可满足牛奶中低新霉素残留量的检测需要.     

Sample preparation for residue determination of gentamicin and neomycin by liquid chromatography

The effect of sample preparation on the determination of gentamicin and neomycin residues in animal tissues was investigated. The extract was mixed with an ion-pair reagent and applied to an octadecyl cartridge. The cartridges were washed with buffer followed by water, and analytes were eluted with ion-pair buffer-acetonitrile mixture. The aminoglycosides were derivatized with 9-fluorenylmethyl chloroformate prior to liquid chromatography using a reversed-phase column and fluorescence detection. Under the conditions applied neomycin was fully separated from all the gentamicin compounds. The highest recoveries of gentamicin and neomycin from spiked tissues were obtained using trichloroacetic acid after initial extraction with phosphate-buffered saline. No interfering peaks from endogenous compounds of matrix were noted at the elution position of the analytes. An intra-laboratory validation of the whole procedure was performed. The calibration graphs were linear from 0.1 to 1.0 mg/kg for gentamicin, and from 0.2 to 1.0 mg/kg for neomycin. Limits of detection were 0.05 mg/kg and 0.10 mg/kg for gentamicin and neomycin, respectively. Limits of quantitation for gentamicin and neomycin were 0.1 and 0.20 mg/kg muscle, liver or kidney tissue, respectively. Recoveries of gentamicin spiked at levels of 0.1 mg/kg porcine tissues ranged from 76 to 86%. Recoveries of neomycin spiked at levels of 0.2 mg/kg porcine tissues ranged from 77 to 83%. The validated procedure was used to determine gentamicin concentrations in porcine tissue after dosing with gentamicin at a level of 5 mg/kg body mass.     

Multisite modification of neomycin B: combined Mitsunobu and click chemistry approach

The aminoglycoside antibiotic neomycin B has been converted into several novel building blocks that can be used for the specific modification of three of the four ring systems. Under carefully controlled conditions, the Mitsunobu reaction can be used to selectively dehydrate the ido ring to give the talo epoxide. Subsequently however, under more forcing conditions, the 2-deoxy streptamine ring undergoes Mitsunobu dehydration to give an aziridine. An unusual remote neighboring group effect was observed. When the primary hydroxyl of the ribose ring was blocked, aziridine formation on the deoxystreptamine ring did not occur. Both the epoxide and epoxide-aziridine neomycin building blocks can be ring-opened with azide and subjected to "click" type chemistry with terminal alkynes to generate a series of new neomycin analogues. These reactions can all be carried out without recourse to O-protecting groups. A detailed conformational analysis by NMR revealed some unexpected conformer preferences in these systems.     

A new class of branched aminoglycosides: pseudo-pentasaccharide derivatives of neomycin B

[reaction: see text] The clinically important antibiotic neomycin B was modified at position C5' ' by adding one extra sugar ring in the beta-configuration, and the observed pseudo-pentasaccharides were tested against various bacterial strains, including pathogenic and resistant strains. The designed antibiotics show antibacterial activity superior to that of neomycin B against pathogenic and resistant bacterial strains.     

Spectrophotometric studies of neomycin-copper complex and determination of neomycin sulfate using an auxiliary ligand

Spectrophotometric investigation of the deep blue colored, water-soluble complex of

1. Stability constant and free energy of formation of Cu-NMS complex at 30 ± 1 °C

     

18.

Nachweis von RNA‐Interferenz im Menschen nach systemischer Gabe von siRNAs     

Jens Kurreck 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2010,122(36):6396-6398

     

19.

Chemically Synthesized,Self-Assembling Small Interfering RNA-Prohead RNA Molecules Trigger Dicer-Independent Gene Silencing     

Dr. Alyssa C. Hill  Dr. Daniël van Leeuwen  Dr. Verena Schlösser  Dr. Alok Behera  Dr. Bogdan Mateescu  Prof. Dr. Jonathan Hall 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(8):e202103995

RNA interference (RNAi) mediated by small interfering RNA (siRNA) duplexes is a powerful therapeutic modality, but the translation of siRNAs from the bench into clinical application has been hampered by inefficient delivery in vivo. An innovative delivery strategy involves fusing siRNAs to a three-way junction (3WJ) motif derived from the phi29 bacteriophage prohead RNA (pRNA). Chimeric siRNA-3WJ molecules are presumed to enter the RNAi pathway through Dicer cleavage. Here, we fused siRNAs to the phi29 3WJ and two phylogenetically related 3WJs. We confirmed that the siRNA-3WJs are substrates for Dicer in vitro. However, our results reveal that siRNA-3WJs transfected into Dicer-deficient cell lines trigger potent gene silencing. Interestingly, siRNA-3WJs transfected into an Argonaute 2-deficient cell line also retain some gene silencing activity. siRNA-3WJs are most efficient when the antisense strand of the siRNA duplex is positioned 5′ of the 3WJ (5′-siRNA-3WJ) relative to 3′ of the 3WJ (3′-siRNA-3WJ). This work sheds light on the functional properties of siRNA-3WJs and offers a design rule for maximizing their potency in the human RNAi pathway.     

20.

Ion-association method for the colorimetric determination of neomycin sulphate in pure and dosage forms     

Amin AS  Issa YM 《Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy》2003,59(4):663-670

A simple, fairly rapid, sensitive and accurate method is described for the colorimetric determination of neomycin sulphate (NMS), based on the measurement of the absorbance of the extracted organic soluble ion-association complex formed between neomycin dictation and a bulky counter anion. Different chromotropic acid azo dyes were examined as counter ions. The effect of pH, the counter ion concentration, sequence of addition and solvents for extraction were also illustrated. The most suitable system is based on reagent VIII (pH 7.5) with chloroform as the extraction solvent. The use of other counter ions, in conjunction with their respective solvents, was found to be less sensitive. The neomycin-reagent VIII system exhibits negligible or no interference when used for the determination of up to 58 microgml(-1) of NMS in the presence of several drug excipiences. The method has been used for the determination of up to 58 microgml(-1) with a good recovery (99.8+/-1.5%), and the precision is supported by the low relative standard deviation 相似文献   

Method	$\text{log}\text{K}{}_{\mathrm{s}}$	ΔF (Kcal/mole)
Mukherji and Dey (4)	4.11	?5.70
Subhrana and Raghavrao (6)	4.80	?6.66

Chemically Synthesized,Self-Assembling Small Interfering RNA-Prohead RNA Molecules Trigger Dicer-Independent Gene Silencing

RNA interference (RNAi) mediated by small interfering RNA (siRNA) duplexes is a powerful therapeutic modality, but the translation of siRNAs from the bench into clinical application has been hampered by inefficient delivery in vivo. An innovative delivery strategy involves fusing siRNAs to a three-way junction (3WJ) motif derived from the phi29 bacteriophage prohead RNA (pRNA). Chimeric siRNA-3WJ molecules are presumed to enter the RNAi pathway through Dicer cleavage. Here, we fused siRNAs to the phi29 3WJ and two phylogenetically related 3WJs. We confirmed that the siRNA-3WJs are substrates for Dicer in vitro. However, our results reveal that siRNA-3WJs transfected into Dicer-deficient cell lines trigger potent gene silencing. Interestingly, siRNA-3WJs transfected into an Argonaute 2-deficient cell line also retain some gene silencing activity. siRNA-3WJs are most efficient when the antisense strand of the siRNA duplex is positioned 5′ of the 3WJ (5′-siRNA-3WJ) relative to 3′ of the 3WJ (3′-siRNA-3WJ). This work sheds light on the functional properties of siRNA-3WJs and offers a design rule for maximizing their potency in the human RNAi pathway.     

Ion-association method for the colorimetric determination of neomycin sulphate in pure and dosage forms

A simple, fairly rapid, sensitive and accurate method is described for the colorimetric determination of neomycin sulphate (NMS), based on the measurement of the absorbance of the extracted organic soluble ion-association complex formed between neomycin dictation and a bulky counter anion. Different chromotropic acid azo dyes were examined as counter ions. The effect of pH, the counter ion concentration, sequence of addition and solvents for extraction were also illustrated. The most suitable system is based on reagent VIII (pH 7.5) with chloroform as the extraction solvent. The use of other counter ions, in conjunction with their respective solvents, was found to be less sensitive. The neomycin-reagent VIII system exhibits negligible or no interference when used for the determination of up to 58 microgml(-1) of NMS in the presence of several drug excipiences. The method has been used for the determination of up to 58 microgml(-1) with a good recovery (99.8+/-1.5%), and the precision is supported by the low relative standard deviation 相似文献