The title compound N-cyanosulfoximine derivative containing 1,2,3-thiadiazole （C6HsN4OS2, Mr = 216.28） has been synthesized using 4-（chloromethyl）-5-methyl-1,2,3-thiadiazole as the starting material, and its struc...The title compound N-cyanosulfoximine derivative containing 1,2,3-thiadiazole （C6HsN4OS2, Mr = 216.28） has been synthesized using 4-（chloromethyl）-5-methyl-1,2,3-thiadiazole as the starting material, and its structure was characterized by IR, 1H NMR, HRMS, elemental analysis and single-crystal X-ray diffraction. The crystal of the title compound belongs to orthorhombic, space group Pna21 with a = 14.730（6）, b = 5.478（2）, c = 22.619（9） A, Z = 8, V = 1825.0（13） A3, Dc = 1.574 g/cm3,/a = 0.547 mm-1, F（000） = 896, R = 0.0767 and wR （I〉 2o（/）） = 0.2064. X-ray analysis indicates that in this crystal double enantiomers are found as the basically asymmetrical unit and interactions between S（1）...N（3）, S（3）...N（4） and S（3）...N（7） are observed. This kind of interactions extends the molecules into a one-dimensional double chain. The preliminary biological test showed that the title compound had insecticidal activity against Myzus persicae in a certain degree and also presented moderate potential bioactivity against tobacco mosaic virus （TMV）.展开更多
AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, H...AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine kinase.RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO.CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.展开更多
A rhodium/diphosphine-catalyzed asymmetric cross-dehydrogenative coupling between sulfoximines and dihydrosilanes has been achieved. This is the first report on the enantioselective N-silylation of sulfoximines. The p...A rhodium/diphosphine-catalyzed asymmetric cross-dehydrogenative coupling between sulfoximines and dihydrosilanes has been achieved. This is the first report on the enantioselective N-silylation of sulfoximines. The protocol gives access to a variety of Si-stereogenic N-silylated sulfoximines in decent yield(up to 99%) with excellent stereoselectivity(up to 99%), featuring high atom economy, and a cleaner manner with H2as the sole byproduct. The obtained bis-Si-stereogenic monohydrosilane product can be further converted into the corresponding chiral polymer with pendant sulfoximine groups.展开更多
The fall armyworm,Spodoptera frugiperda(S.frugiperda),represents the most resistant insect species and poses serious threat to grain yield.Chlorantraniliprole(CHL),which targets the ryanodine receptors(RyRs)in insects...The fall armyworm,Spodoptera frugiperda(S.frugiperda),represents the most resistant insect species and poses serious threat to grain yield.Chlorantraniliprole(CHL),which targets the ryanodine receptors(RyRs)in insects,has demonstrated the efficacy in controlling S.frugiperda.Nevertheless,this has led to emerging resistance in several countries.To counter this resistance,a viable approach involves the development of novel compounds that bind against RyRs via distinct binding sites or modes.In this study,a series of 22 novel anthranilic diamide derivatives was designed and synthesized,and their insecticidal activities were evaluated.Most of these derivatives showed moderate to good insecticidal activity against S.frugiperda and Mythimna separata.Time-lapse fluorescence measurements of endoplasmic reticulum luminal calcium revealed that most derivatives elicited cellular responses similar as CHL when assessed on HEK293 cells expressing S.frugiperda ryanodine receptors(SfRyRs).The mode of action of compound 13a was studied and verified on the isolated neurons by calcium imaging technique.Finally,molecular docking analysis was employed to predict the binding mechanism of compound 13a against SfRyRs.Overall,these novel diamide derivatives hold promise as a valuable resource for guiding the future design of insecticidal compounds targeting RyRs.展开更多
基金funded in part by the National Natural Science Foundation of China(21372132)Nataliya P.Belskaya thanks Russian State Task of Ministry Education and Science No.4.560.2014K.Kalinina A.Tatiana thanks RFBF№13-03-00137
文摘The title compound N-cyanosulfoximine derivative containing 1,2,3-thiadiazole （C6HsN4OS2, Mr = 216.28） has been synthesized using 4-（chloromethyl）-5-methyl-1,2,3-thiadiazole as the starting material, and its structure was characterized by IR, 1H NMR, HRMS, elemental analysis and single-crystal X-ray diffraction. The crystal of the title compound belongs to orthorhombic, space group Pna21 with a = 14.730（6）, b = 5.478（2）, c = 22.619（9） A, Z = 8, V = 1825.0（13） A3, Dc = 1.574 g/cm3,/a = 0.547 mm-1, F（000） = 896, R = 0.0767 and wR （I〉 2o（/）） = 0.2064. X-ray analysis indicates that in this crystal double enantiomers are found as the basically asymmetrical unit and interactions between S（1）...N（3）, S（3）...N（4） and S（3）...N（7） are observed. This kind of interactions extends the molecules into a one-dimensional double chain. The preliminary biological test showed that the title compound had insecticidal activity against Myzus persicae in a certain degree and also presented moderate potential bioactivity against tobacco mosaic virus （TMV）.
基金Supported by Grants from SAF2008-05355CCG07-UAH/BIO-2085
文摘AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine kinase.RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO.CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.
基金financial support from the National Natural Science Foundation of China (Nos.22122102, 22101120, 22271134)Guangdong Provincial Key Laboratory of Catalysis (No.2020B121201002)+2 种基金Guangdong Pearl River Talent Program (No.2019QN01Y628)Shenzhen Science and Technology Innovation Committee (No.RCJC20221008092723013)Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education (No.KFJJ2022012)。
文摘A rhodium/diphosphine-catalyzed asymmetric cross-dehydrogenative coupling between sulfoximines and dihydrosilanes has been achieved. This is the first report on the enantioselective N-silylation of sulfoximines. The protocol gives access to a variety of Si-stereogenic N-silylated sulfoximines in decent yield(up to 99%) with excellent stereoselectivity(up to 99%), featuring high atom economy, and a cleaner manner with H2as the sole byproduct. The obtained bis-Si-stereogenic monohydrosilane product can be further converted into the corresponding chiral polymer with pendant sulfoximine groups.
基金Nankai University Cangzhou Bohai New Area Green Chemical Research Institute(NCC)Fund,the National Natural Science Foundation of China(Nos.31972287,32022073)the National Key Research and Development Program of China(No.2022YFE0108400)the Scientific Project of Tianjin Municipal Education Commission,China(No.2022KJ026).
文摘The fall armyworm,Spodoptera frugiperda(S.frugiperda),represents the most resistant insect species and poses serious threat to grain yield.Chlorantraniliprole(CHL),which targets the ryanodine receptors(RyRs)in insects,has demonstrated the efficacy in controlling S.frugiperda.Nevertheless,this has led to emerging resistance in several countries.To counter this resistance,a viable approach involves the development of novel compounds that bind against RyRs via distinct binding sites or modes.In this study,a series of 22 novel anthranilic diamide derivatives was designed and synthesized,and their insecticidal activities were evaluated.Most of these derivatives showed moderate to good insecticidal activity against S.frugiperda and Mythimna separata.Time-lapse fluorescence measurements of endoplasmic reticulum luminal calcium revealed that most derivatives elicited cellular responses similar as CHL when assessed on HEK293 cells expressing S.frugiperda ryanodine receptors(SfRyRs).The mode of action of compound 13a was studied and verified on the isolated neurons by calcium imaging technique.Finally,molecular docking analysis was employed to predict the binding mechanism of compound 13a against SfRyRs.Overall,these novel diamide derivatives hold promise as a valuable resource for guiding the future design of insecticidal compounds targeting RyRs.
