Ethaselen, an organoselenium compound designed and synthesized in the School of Pharmaceutical Sciences, Peking University, has been entitled to independent intellectual property rights both at home and abroad. As one...Ethaselen, an organoselenium compound designed and synthesized in the School of Pharmaceutical Sciences, Peking University, has been entitled to independent intellectual property rights both at home and abroad. As one of the novel antitumor drugs, ethaselen has been extensively studied in Phase I clinical trial, and its biological target is thioredoxin reductase. In this review, we focus on the ethaselen＇s efficacy and pharmacological actions, including antitumor effects both in vitro and in vivo, and immunologic functions. These research findings not only provide the theoretical basis for the anticancer study of ethaselen, but also guide the clinical trial of ethaselen.展开更多
A novel organoselenium compound,WB（1,2-[bis（1,2-benzisoselenazolone-3（2H）-ketone）]pentane） has indicated anti-tumor activity.Its pharmacokinetic data has never been determined.By using the H22 tumor bearing mous...A novel organoselenium compound,WB（1,2-[bis（1,2-benzisoselenazolone-3（2H）-ketone）]pentane） has indicated anti-tumor activity.Its pharmacokinetic data has never been determined.By using the H22 tumor bearing mouse model,the tissue distribution of WB after single and four consecutive doses（both were 120 mg/kg/d） was explored.The selenium content of the tissues was used as an indicator of WB absorption,distribution and metabolism.The selenium in the heart,liver, spleen,kidneys,lungs,stomach,pancreas,brain,colon,intestine,testes,plasma,and tumor were determined by generation atomic fluorescence spectrometry（AFS）.With single or multiple oral administration of WB,the selenium content significantly increased in the liver,stomach,colon,and intestine.The selenium content in the spleen,lungs,pancreas,testes,plasma and tumor also increased compared with the controls;but no significant changes were found in the brain and kidney.WB and its metabolites distributed predominantly in the colon,liver,stomach and intestine,which resulted in a significant increase in the selenium content in both groups.There was no observed significant accumulation of WB in the vital organs.展开更多
Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming ...Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming mice (dosage, 0.1 g·kg^(-1)·d^(-1)) intragastrically for 7 successive days. The contents of selenium in heart, liver, spleen, kidneys, lungs, stomach, brain, muscle, and bone were determined by fluorometric method on the eighth day. MTT assay was used to study tumor growth inhibition of Eb in vitro, and lymphocyte transformation, hemolysin formation and phagocytosis assay were used to study its immunocompetence. Results After 7 days′ administration of Eb, the tissue contents of sele-(nium) in liver, spleen, lungs, kidneys, and bone of mice increased, especially those in liver and spleen increased significan-tly, compared with controls; but no significant changes of such contents were found in muscle, heart, brain, and stomach. Eb demonstrated inhibitory effects on human Bel-7402, BGC-823, and Calu-3 cancer cell lines in vitro. Eb also showed ability to enhance lymphocyte transformation and serum hemolysin formation in vitro and increase the phagocytosis of macrophages. Conclusion The validated antitumor and immunostimulatory activities of Eb suggest a hypothesis that Eb may behave as a biological response modifier when used as an antitumor agent. Eb is worthy of further study in developing a new antineoplastic and immunity enhancing agent in the light of its antitumor activity, immunocompetence and specific distribution in liver, lungs, kidneys, bone, and spleen.展开更多
Radicals featuringπ-conjugated systems have garnered extensive attention due to their intriguing structures and unique physicochemical properties.However,open-shell polycyclic aromatic hydrocarbons(PAHs)with columnar...Radicals featuringπ-conjugated systems have garnered extensive attention due to their intriguing structures and unique physicochemical properties.However,open-shell polycyclic aromatic hydrocarbons(PAHs)with columnar stacking architectures remain scarce.Herein,we present three novel seleniumcontaining open-shell PAHs with well-defined solid-state packing patterns.The radical species[4Se-PAH]_(3)[BAr_(4)^(F )]_(2) and[4Se-PAH]_(2)[SbF_(6)]_(2) assemble into columnar stacks,whereas[4Se-PAH]_(4)[Al(OR^(F))_(4)]_(4) adopts a discrete tetrameric stacking arrangement,in which fourπ-scaffolds are fully separated by counterions[Al(OR^(F))_(4)]^(-).Single-crystal X-ray analysis reveals shortened Se-Se bonds(2.2863(12)-2.3074(12)A)and near-planar geometries,suggesting partialπ-bond character,which is further supported by theoretical calculations.Electron paramagnetic resonance spectroscopy unequivocally confirmed the radical nature of all three species.Pressure-dependent conductivity measurements show that both[4Se-PAH]_(4)[Al(OR^(F))_(4)]_(4) and[4Se-PAH]_(2)[SbF_(6)]_(2) exhibit high electrical conductivity.These findings offer a rare example ofπ-stacked selenium radical systems with tunable packing structures and electronic properties.展开更多
Selenoester compounds exhibit significant biological activity and are widely used in the synthesis of natural products,protein intermediates,and superconducting materials.However,the current methods for constructing s...Selenoester compounds exhibit significant biological activity and are widely used in the synthesis of natural products,protein intermediates,and superconducting materials.However,the current methods for constructing selenoesters suffer from drawbacks such as expensive catalysts,multiple reaction steps,low yields,and poor efficiency to sterically hindered acyl chlorides.Here,an efficient indium-promoted method for the synthesis of Se-aryl-2,2-dimethylbutaneselenoates is developed.The strategy features broad substrate scope,mild reaction conditions and simple operation,offering the desired products in moderate to excellent yields.Furthermore,the gram-scale reaction can be conducted smoothly,laying the foundation for subsequent derivatization of such structures.展开更多
In our previous study,a novel organic selenium compound Eb was synthesized and found to have significant antitumor activity with much less toxicity compared with the leading compound Ebselen.Unfortunately,Eb was pract...In our previous study,a novel organic selenium compound Eb was synthesized and found to have significant antitumor activity with much less toxicity compared with the leading compound Ebselen.Unfortunately,Eb was practically insoluble in water （2.57 μg/mL） and had very low oral bioavailability,thus its clinical application was greatly limited.In the present study,the inclusion complex of Eb with 2-hydroxypropyl-β-cyclodextrin （HP-βCD） was prepared and pharmacokinetics of Eb and the inclusion complex were investigated.The water solubility of Eb was dramatically enhanced by inclusion with HP-βCD,which reached 8.4 mg/mL.The pharmacokinetic study showed that the elimination half-life （t 1/2β） of Eb was between 22 h and 30 h and the distribution half-life （t 1/2α） of Eb was 1 h.The results indicated that Eb was rapidly distributed to tissues but slowly eliminated in rats.The absolute bioavailability of Eb/HP-βCD inclusion complex solution through the oral route was 28.3%,and it was 1552% that of Eb in its pure form.In summary,the absorption of Eb in the Eb/HP-βCD inclusion complex was better and faster than that of Eb in its pure form.展开更多
基金National Natural Science Foundation of China(Grant No.30472036)
文摘Ethaselen, an organoselenium compound designed and synthesized in the School of Pharmaceutical Sciences, Peking University, has been entitled to independent intellectual property rights both at home and abroad. As one of the novel antitumor drugs, ethaselen has been extensively studied in Phase I clinical trial, and its biological target is thioredoxin reductase. In this review, we focus on the ethaselen＇s efficacy and pharmacological actions, including antitumor effects both in vitro and in vivo, and immunologic functions. These research findings not only provide the theoretical basis for the anticancer study of ethaselen, but also guide the clinical trial of ethaselen.
基金National Major Projects on Drug Research and Technology(Grant No.2009ZX09103-032)
文摘A novel organoselenium compound,WB（1,2-[bis（1,2-benzisoselenazolone-3（2H）-ketone）]pentane） has indicated anti-tumor activity.Its pharmacokinetic data has never been determined.By using the H22 tumor bearing mouse model,the tissue distribution of WB after single and four consecutive doses（both were 120 mg/kg/d） was explored.The selenium content of the tissues was used as an indicator of WB absorption,distribution and metabolism.The selenium in the heart,liver, spleen,kidneys,lungs,stomach,pancreas,brain,colon,intestine,testes,plasma,and tumor were determined by generation atomic fluorescence spectrometry（AFS）.With single or multiple oral administration of WB,the selenium content significantly increased in the liver,stomach,colon,and intestine.The selenium content in the spleen,lungs,pancreas,testes,plasma and tumor also increased compared with the controls;but no significant changes were found in the brain and kidney.WB and its metabolites distributed predominantly in the colon,liver,stomach and intestine,which resulted in a significant increase in the selenium content in both groups.There was no observed significant accumulation of WB in the vital organs.
文摘Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming mice (dosage, 0.1 g·kg^(-1)·d^(-1)) intragastrically for 7 successive days. The contents of selenium in heart, liver, spleen, kidneys, lungs, stomach, brain, muscle, and bone were determined by fluorometric method on the eighth day. MTT assay was used to study tumor growth inhibition of Eb in vitro, and lymphocyte transformation, hemolysin formation and phagocytosis assay were used to study its immunocompetence. Results After 7 days′ administration of Eb, the tissue contents of sele-(nium) in liver, spleen, lungs, kidneys, and bone of mice increased, especially those in liver and spleen increased significan-tly, compared with controls; but no significant changes of such contents were found in muscle, heart, brain, and stomach. Eb demonstrated inhibitory effects on human Bel-7402, BGC-823, and Calu-3 cancer cell lines in vitro. Eb also showed ability to enhance lymphocyte transformation and serum hemolysin formation in vitro and increase the phagocytosis of macrophages. Conclusion The validated antitumor and immunostimulatory activities of Eb suggest a hypothesis that Eb may behave as a biological response modifier when used as an antitumor agent. Eb is worthy of further study in developing a new antineoplastic and immunity enhancing agent in the light of its antitumor activity, immunocompetence and specific distribution in liver, lungs, kidneys, bone, and spleen.
基金Natural Science Foundation(grant kq2502053)the National Natural Science Foundation of China(grant 22271086,U24A2020481).
文摘Radicals featuringπ-conjugated systems have garnered extensive attention due to their intriguing structures and unique physicochemical properties.However,open-shell polycyclic aromatic hydrocarbons(PAHs)with columnar stacking architectures remain scarce.Herein,we present three novel seleniumcontaining open-shell PAHs with well-defined solid-state packing patterns.The radical species[4Se-PAH]_(3)[BAr_(4)^(F )]_(2) and[4Se-PAH]_(2)[SbF_(6)]_(2) assemble into columnar stacks,whereas[4Se-PAH]_(4)[Al(OR^(F))_(4)]_(4) adopts a discrete tetrameric stacking arrangement,in which fourπ-scaffolds are fully separated by counterions[Al(OR^(F))_(4)]^(-).Single-crystal X-ray analysis reveals shortened Se-Se bonds(2.2863(12)-2.3074(12)A)and near-planar geometries,suggesting partialπ-bond character,which is further supported by theoretical calculations.Electron paramagnetic resonance spectroscopy unequivocally confirmed the radical nature of all three species.Pressure-dependent conductivity measurements show that both[4Se-PAH]_(4)[Al(OR^(F))_(4)]_(4) and[4Se-PAH]_(2)[SbF_(6)]_(2) exhibit high electrical conductivity.These findings offer a rare example ofπ-stacked selenium radical systems with tunable packing structures and electronic properties.
基金Project supported by the Early-Career Young Scientists and Technologists Project of Jiangxi Province(No.20244BCE52224)ant the Jiangxi Provincial Natural Science Foundation(No.20252BAC200240)。
文摘Selenoester compounds exhibit significant biological activity and are widely used in the synthesis of natural products,protein intermediates,and superconducting materials.However,the current methods for constructing selenoesters suffer from drawbacks such as expensive catalysts,multiple reaction steps,low yields,and poor efficiency to sterically hindered acyl chlorides.Here,an efficient indium-promoted method for the synthesis of Se-aryl-2,2-dimethylbutaneselenoates is developed.The strategy features broad substrate scope,mild reaction conditions and simple operation,offering the desired products in moderate to excellent yields.Furthermore,the gram-scale reaction can be conducted smoothly,laying the foundation for subsequent derivatization of such structures.
基金Natural Science Foundation of Beijing (Grant No. 7021001)the Foundation for the Special Program of the Following Novel Candidate Drug by Beijing S&T Committee (Grant No. H20220060190)National Natural Science Foundation (Grant No.30472036)
文摘In our previous study,a novel organic selenium compound Eb was synthesized and found to have significant antitumor activity with much less toxicity compared with the leading compound Ebselen.Unfortunately,Eb was practically insoluble in water （2.57 μg/mL） and had very low oral bioavailability,thus its clinical application was greatly limited.In the present study,the inclusion complex of Eb with 2-hydroxypropyl-β-cyclodextrin （HP-βCD） was prepared and pharmacokinetics of Eb and the inclusion complex were investigated.The water solubility of Eb was dramatically enhanced by inclusion with HP-βCD,which reached 8.4 mg/mL.The pharmacokinetic study showed that the elimination half-life （t 1/2β） of Eb was between 22 h and 30 h and the distribution half-life （t 1/2α） of Eb was 1 h.The results indicated that Eb was rapidly distributed to tissues but slowly eliminated in rats.The absolute bioavailability of Eb/HP-βCD inclusion complex solution through the oral route was 28.3%,and it was 1552% that of Eb in its pure form.In summary,the absorption of Eb in the Eb/HP-βCD inclusion complex was better and faster than that of Eb in its pure form.
文摘目的:检测新型有机硒化合物双硒唑烷-1(Ethaselen-1,Eb1)的动物体内免疫调节作用。方法:建立Lew-is肺癌(Lew is lung cancer,LLC)皮下移植瘤C57/BL鼠动物模型,选取25.0 mg/kg和12.5 mg/kg两个剂量的Eb1作为实验药物,以左旋咪唑(levam isole,LMS)2.0 mg/kg作为阳性对照,以溶剂5 g/L羧甲基纤维素钠溶液为阴性对照,于接种肿瘤后第2天开始向C57/BL鼠腹腔连续注射7 d药物,探讨Eb1对正常及肿瘤鼠的相对脾重、脾淋巴细胞转化活性、自然杀伤(natural k iller,NK)细胞活性、淋巴因子-激活杀伤(lymphok ine-activated k iller,LAK)细胞活性及淋巴细胞CD4+,CD8+亚群阳性细胞百分数的影响。结果:高剂量Eb1能够使正常鼠和肿瘤鼠的相对脾重增加150.59%和122.55%,脾淋巴细胞转化活性增加162.25%和561.98%,NK细胞活性增加78.60%和219.42%,脾淋巴细胞CD4-CD8+亚群阳性细胞百分含量增加104.72%和105.87%,高剂量Eb1亦能使肿瘤鼠的LAK细胞活性增加195.11%,与对照组相比差异均有统计学意义(P<0.01)。结论:新型有机硒化合物Eb1在C57/BL小鼠体内具有明显的免疫调节作用。
