Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated intracellularly where it competitively inhibits cytidine incorporation into DNA strands. Another mechanism-of-action of gemcitabine (diphosp...Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated intracellularly where it competitively inhibits cytidine incorporation into DNA strands. Another mechanism-of-action of gemcitabine (diphosphorylated form) involves irreversible inhibition of the enzyme ribonucleotide reductase thereby preventing deoxyribonucleotide synthesis. Functioning as a potent chemotherapeutic gemcitabine promote decreases in neoplastic cell proliferation and apoptosis which is frequently found to be effective for the treatment of several leukemias and a wide spectrum of carcinomas. A brief plasma half-life in part due to rapid deamination and chemotherapeutic-resistance restricts the utility of gemcitabine in clinical oncology. Selective “targeted” delivery of gemcitabine represents a potential molecular strategy for simultaneously prolonging its plasma half-life and minimizing innocient tissues and organ systems exposure to chemotherapy. The molecular design and an organic chemistry based synthesis reaction is described that initially generates a UV-photoactivated gemcitabine intermediate. In a subsequent phase of the synthesis method the UV-photoactivated gemcitabine intermediate is covalently bonded to a monoclonal immunoglobulin yielding an end-product in the form of gemcitabine-(C4-amide)-[anti-HER2/neu]. Analysis by SDS-PAGE/chemiluminescent auto-radiography did not detect evidence of gemcitabine-(C4-amide)-[anti-HER2/neu] polymerization or degradative fragmentation while cell-ELISA demonstrated retained binding-avidity for HER2/neu trophic membrane receptor complexes highly over-expressed by chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3). Compared to chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3), the covalent immunochemotherapeutic, gemcitabine-(C4-amide)-[anti-HER2/neu] is anticipated to exert greater levels of cytotoxic anti-neoplastic potency against other neoplastic cell types like pancreatic carcinoma, small-cell lung carcinoma, neuroblastoma, glioblastoma, oral squamous c展开更多
In this study, we proposed a novel method to investigate the advanced oxidation process of neonicotinoids(NNIs) from the perspective of concomitant chemiluminescence(CL) reaction. It was found that in the presence of ...In this study, we proposed a novel method to investigate the advanced oxidation process of neonicotinoids(NNIs) from the perspective of concomitant chemiluminescence(CL) reaction. It was found that in the presence of cobalt ions with cyanoimino NNIs, acetamiprid(ACE) and thiacloprid(THI), could promote peroxymonosulfate and Ru(bpy)_(3)^(2+) to produce strong CL, but no CL occurred with nitro-involved NNIs as alternatives. Experimental dada from UV absorption spectra and chemiluminescence spectra suggested that new cyclic compounds might be formed during the reaction. Based on the results of free radical scavenging experiment and mass spectra, a new degradation and reaction mechanism of cyanoiminocontaining NNIs was proposed. ACE or THI were first attacked by SO_(4)^(·-) to form benzyl radicals, which in turn reacted with the carbon atoms of cyano group through electrophilic addition reaction in the formation of intramolecular ring. Then a redox reaction between Ru(bpy)_(3)^(3+) and imino group immediately took place with CL emission(610 nm). The new mechanistic knowledge would be meaningful for other contaminants for their interactions with PMS.展开更多
文摘Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated intracellularly where it competitively inhibits cytidine incorporation into DNA strands. Another mechanism-of-action of gemcitabine (diphosphorylated form) involves irreversible inhibition of the enzyme ribonucleotide reductase thereby preventing deoxyribonucleotide synthesis. Functioning as a potent chemotherapeutic gemcitabine promote decreases in neoplastic cell proliferation and apoptosis which is frequently found to be effective for the treatment of several leukemias and a wide spectrum of carcinomas. A brief plasma half-life in part due to rapid deamination and chemotherapeutic-resistance restricts the utility of gemcitabine in clinical oncology. Selective “targeted” delivery of gemcitabine represents a potential molecular strategy for simultaneously prolonging its plasma half-life and minimizing innocient tissues and organ systems exposure to chemotherapy. The molecular design and an organic chemistry based synthesis reaction is described that initially generates a UV-photoactivated gemcitabine intermediate. In a subsequent phase of the synthesis method the UV-photoactivated gemcitabine intermediate is covalently bonded to a monoclonal immunoglobulin yielding an end-product in the form of gemcitabine-(C4-amide)-[anti-HER2/neu]. Analysis by SDS-PAGE/chemiluminescent auto-radiography did not detect evidence of gemcitabine-(C4-amide)-[anti-HER2/neu] polymerization or degradative fragmentation while cell-ELISA demonstrated retained binding-avidity for HER2/neu trophic membrane receptor complexes highly over-expressed by chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3). Compared to chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3), the covalent immunochemotherapeutic, gemcitabine-(C4-amide)-[anti-HER2/neu] is anticipated to exert greater levels of cytotoxic anti-neoplastic potency against other neoplastic cell types like pancreatic carcinoma, small-cell lung carcinoma, neuroblastoma, glioblastoma, oral squamous c
基金financial supports from the National Natural Science Foundation of China(Nos.81960600and 81760601)the Natural Science Foundation of Jiangxi Province(Nos.20192BAB205089 and 20192BAB205091)。
文摘In this study, we proposed a novel method to investigate the advanced oxidation process of neonicotinoids(NNIs) from the perspective of concomitant chemiluminescence(CL) reaction. It was found that in the presence of cobalt ions with cyanoimino NNIs, acetamiprid(ACE) and thiacloprid(THI), could promote peroxymonosulfate and Ru(bpy)_(3)^(2+) to produce strong CL, but no CL occurred with nitro-involved NNIs as alternatives. Experimental dada from UV absorption spectra and chemiluminescence spectra suggested that new cyclic compounds might be formed during the reaction. Based on the results of free radical scavenging experiment and mass spectra, a new degradation and reaction mechanism of cyanoiminocontaining NNIs was proposed. ACE or THI were first attacked by SO_(4)^(·-) to form benzyl radicals, which in turn reacted with the carbon atoms of cyano group through electrophilic addition reaction in the formation of intramolecular ring. Then a redox reaction between Ru(bpy)_(3)^(3+) and imino group immediately took place with CL emission(610 nm). The new mechanistic knowledge would be meaningful for other contaminants for their interactions with PMS.
