Designing Functionally Substituted Pyridine-Carbohydrazides for Potent Antibacterial and Devouring Antifungal Effect on Multidrug Resistant (MDR) Strains

The emergence of multidrug-resistant (MDR) pathogens and the gradual depletion of available antibiotics have exacerbated the need for novel antimicrobial agents with minimal toxicity. Herein, we report functionally substituted pyridine carbohydrazide with remarkable antimicrobial effect on multi-drug resistant strains. In the series, compound 6 had potent activity against four MDR strains of Candida spp., with minimum inhibitory concentration (MIC) values being in the range of 16–24 µg/mL and percentage inhibition up to 92.57%, which was exceptional when compared to broad-spectrum antifungal drug fluconazole (MIC = 20 µg/mL, 81.88% inhibition). Substitution of the octyl chain in 6 with a shorter butyl chain resulted in a significant anti-bacterial effect of 4 against Pseudomonas aeruginosa (ATCC 27853), the MIC value being 2-fold superior to the standard combination of ampicillin/cloxacillin. Time-kill kinetics assays were used to discern the efficacy and pharmacodynamics of the potent compounds. Further, hemolysis tests confirmed that both compounds had better safety profiles than the standard drugs. Besides, molecular docking simulations were used to further explore their mode of interaction with target proteins. Overall results suggest that these compounds have the potential to become promising antimicrobial drugs against MDR strains.     

A New Electrochemical Method for the Determination of Proteins with Cupferron‐Cadmium(II) Complex

A new electrochemical method was proposed for the determination of trace amounts of proteins based on the cupferron (Cup) and cadmium(II) complex [Cup‐Cd(II)] as the voltammetric probe. In the selected pH 6.5 Britton–Robinson (B–R) buffer solution, Cup can interact with Cd(II) to form a stable complex of [Cup‐Cd(II)], which had a sensitive linear sweep voltammetric reductive peak at ?0.654 V (vs. SCE). The addition of human serum albumin (HSA) into [Cup‐Cd(II)] complex solution could greatly decrease the reductive peak current without the change of the reductive peak potential, which indicated that HSA could interact with [Cup‐Cd(II)] complex to form a supramolecular biocomplex. The interaction mechanism was discussed and the decrease of reductive peak current was proportional to the concentration of HSA, which could be further used for the proteins determination. The optimal conditions of the binding reaction and the electrochemical detection were carefully investigated. Under the optimal conditions a new quantitative determination method for different kinds of proteins such as HSA, bovine serum albumin (BSA) and bovine hemoglobin (BHb) etc. was developed. The proposed method was simple, practical and relatively free from the interferences of coexisting substances, and it was further applied to the samples determination with satisfactory results. The binding constant (β_s) and the binding number (m) of HSA with [Cup‐Cd(II)] complex were calculated by the voltammetric data with the results as β_s=1.12×10⁶ and m=1.     

新荧光增敏法测定人血清蛋白质

合成了新荧光试剂5-(4-羧基苯偶氮)-8-水杨醛缩氨基喹啉(p-CPSAQ),探讨了与人血清蛋白反应的最佳实验条件.在pH=7.0的缓冲体系中,蛋白质的存在使p-CPSAQ的荧光大大增强,据此建立了测定人血清蛋白质的灵敏方法;对人血清白蛋白和γ-球蛋白的线性范围分别为0.1～4.5 mg/L和 0.1～4.0 mg/L;检出限分别为0.028和0.027 mg/L.方法灵敏、快速、选择性好,用于人血清样品中总蛋白的测定,结果满意.     

Poly(ethylene glycol)–polyethyleneimine NanoGel™ particles: novel drug delivery systems for antisense oligonucleotides

A novel type of drug delivery system, termed NanoGel™ is proposed. NanoGel™ represent particles of a hydrophilic polymer network that were synthesized by cross-linking of polyethyleneimine (PEI) and carbonyldiimidazole-activated poly(ethylene glycol) (PEG) using emulsification/solvent evaporation technique. The resulting NanoGel™ was fractionated by gel-permeation chromatography. A major fraction with an average particle size of 120 nm was used in further experiments. Antisense phosphorothioate oligonucleotides (SODN) specific to human mdr1 gene were incorporated in these NanoGel™ particles. Loading of NanoGel™ particles with SODN resulted in reduction of the particle effective diameter to 80 nm and decreased zeta-potential due to neutralization of the charge of PEI chains by SODN. Accumulation of SODN incorporated in NanoGel™ particles in multidrug resistant (MDR) human oral epidermoid carcinoma cells (KBv) was significantly increased compared to the free SODN. Furthermore, efficient transport of SODN-loaded NanoGel™ particles across polarized monolayers of human intestinal epithelial cells (Caco-2) was demonstrated. Finally, antisense SODNs incorporated in NanoGel™ particles were found to effectively inhibit expression of P-glycoprotein (P-gp) efflux pump in MDR cell lines.     

A Facile Synthetic Method for （3Z, 6Z, 9S, 10R）-9, 10-Epoxy-3, 6- heneicosadiene, Sex Pheromone Component of Hyphantria Cunea （Drug）

Total synthesis of (3Z, 6Z, 9S, 10R)-9, 10-epoxy-3, 6-heneicosadiene, sex pheromone component of Hyphantria cunea (Drug), was achieved using Sharpless AE kinetic resolution and alkylative epoxide rearrangement as key steps.