In this paper, we report the design and moleculardocking study of analogues of antimycin A3 as inhibitors of anti-apoptotic Bcl-2 of breast cancer. Twenty designed compounds and the original antimycin A3 were docked b...In this paper, we report the design and moleculardocking study of analogues of antimycin A3 as inhibitors of anti-apoptotic Bcl-2 of breast cancer. Twenty designed compounds and the original antimycin A3 were docked based on their interaction with breast tumor receptor binding target Bcl-2. The docking resulted in the five top-ranked compounds, namely, compounds 11, 14, 15, 16, and 20, which have a lower G binding energy, better affinity and stronger hydrogen bonding interactions to the active site of Bcl-2 than antimycin A3. Among those five top-ranked compounds, analogue compounds 11 and 14, which have an 18-membered tetralactone core and 18-membered tetraol core, respectively, exhibited the strongest hydrogen bond interaction, formed high stability conformation, and demonstrated the greatest inhibitory activity on the catalytic site of Bcl-2.展开更多
通过A n tim yc in A17对纯培养条件下及回接茄子褐纹病菌[P hom op sis vex ans(Sacc.et Syd)H arter]的影响,发现A n tim yc in A17对茄褐纹病菌菌丝及其甲型孢子都有较强的抑制作用,其抑制中浓度(EC50)分别为0.1000μg/mL和0.0166μg...通过A n tim yc in A17对纯培养条件下及回接茄子褐纹病菌[P hom op sis vex ans(Sacc.et Syd)H arter]的影响,发现A n tim yc in A17对茄褐纹病菌菌丝及其甲型孢子都有较强的抑制作用,其抑制中浓度(EC50)分别为0.1000μg/mL和0.0166μg/mL;经A n tim yc in A17处理过的菌丝体所形成的甲型孢子,其萌发力和形态都较正常孢子有很大差别。展开更多
Reactive oxygen species(ROS)play a vital role in cell signaling and redox regulation,but when present in excess,lead to numerous pathologies.Detailed quantitative characterization of mitochondrial superoxide anion(O^(...Reactive oxygen species(ROS)play a vital role in cell signaling and redox regulation,but when present in excess,lead to numerous pathologies.Detailed quantitative characterization of mitochondrial superoxide anion(O^(·-)_(2))production in fetal pulmonary artery endothelia cells(PAECs)has never been reported.The aim of this study is to assess mitochondrial O^(·-)_(2)pro-duction in cultured PAECs over time using a novel quantitative optical approach.The rate,the sources,and the dynamics of O^(·-)_(2)production were assessed using targeted metabolic modulators of the mitochondrial electron transport chain(ETC)complexes,specifically an uncoupler and inhibitors of the various ETC complexes,and inhibitors of extra-mitochondrial sources of O^(·-)_(2).After stabilization,the cells were loaded with nanomolar mitochondrial-targeted hydroethidine(Mito-HE,MitoSOX)online during the experiment without washout of the residual dye.Time-lapse fuorescence microscopy was used to monitor the dynamic changes in O^(·-)_(2)fluorescence intensity over time in PAECs.The transient behaviors of the fuorescence time course showed exponential increases in the rate of O^(·-)_(2) production in the presence of the ETC uncoupler or inhibitors.The most dramatic and the fastest increase in O^(·-)_(2)production was observed when the cells were treated with the uncoupling agent,PCP.We also showed that only the complex IV inhibitor,KCN,attenuated the marked surge in O^(·-)_(2)production induced by PCP.The results showed that mitochondrial respiratory complexes I,III and IV are sources of O^(·-)_(2) production in PAECs,and a new observation that ROS production during uncoupling of mitochondrial res-piration is mediated in part via complex IV.This novel method can be applied in other studies that examine ROS production under stress condition and during ROS mediated injuries in vritro.展开更多
文摘In this paper, we report the design and moleculardocking study of analogues of antimycin A3 as inhibitors of anti-apoptotic Bcl-2 of breast cancer. Twenty designed compounds and the original antimycin A3 were docked based on their interaction with breast tumor receptor binding target Bcl-2. The docking resulted in the five top-ranked compounds, namely, compounds 11, 14, 15, 16, and 20, which have a lower G binding energy, better affinity and stronger hydrogen bonding interactions to the active site of Bcl-2 than antimycin A3. Among those five top-ranked compounds, analogue compounds 11 and 14, which have an 18-membered tetralactone core and 18-membered tetraol core, respectively, exhibited the strongest hydrogen bond interaction, formed high stability conformation, and demonstrated the greatest inhibitory activity on the catalytic site of Bcl-2.
文摘通过A n tim yc in A17对纯培养条件下及回接茄子褐纹病菌[P hom op sis vex ans(Sacc.et Syd)H arter]的影响,发现A n tim yc in A17对茄褐纹病菌菌丝及其甲型孢子都有较强的抑制作用,其抑制中浓度(EC50)分别为0.1000μg/mL和0.0166μg/mL;经A n tim yc in A17处理过的菌丝体所形成的甲型孢子,其萌发力和形态都较正常孢子有很大差别。
基金supported by the Funds of the Chinese Academy of Sciences for Key Topics in Innovation Engineering(KZCX2-YW-216,KSCX2-YW-G-065,KSCX2-YW-G-073)Natural Science Funds of South China Sea Institute of Oceanology for Young Scholar(SQ200903)+1 种基金Funds of Frontier Areas of SCSIO (LYQY200805)Open Project Program of Key Laboratory of Marine Bio-resources Sustainable Utilization(LMB091013)
基金supported by a grant from UWM research growth initiative(101×290)to MR,grants R01 HL057268 and Muma Endowed Chair in Neonatology to GGK,NIH grant P01-GM-066730-12 to AKSC,and NIH grant 1R15HL129209 to SHA.
文摘Reactive oxygen species(ROS)play a vital role in cell signaling and redox regulation,but when present in excess,lead to numerous pathologies.Detailed quantitative characterization of mitochondrial superoxide anion(O^(·-)_(2))production in fetal pulmonary artery endothelia cells(PAECs)has never been reported.The aim of this study is to assess mitochondrial O^(·-)_(2)pro-duction in cultured PAECs over time using a novel quantitative optical approach.The rate,the sources,and the dynamics of O^(·-)_(2)production were assessed using targeted metabolic modulators of the mitochondrial electron transport chain(ETC)complexes,specifically an uncoupler and inhibitors of the various ETC complexes,and inhibitors of extra-mitochondrial sources of O^(·-)_(2).After stabilization,the cells were loaded with nanomolar mitochondrial-targeted hydroethidine(Mito-HE,MitoSOX)online during the experiment without washout of the residual dye.Time-lapse fuorescence microscopy was used to monitor the dynamic changes in O^(·-)_(2)fluorescence intensity over time in PAECs.The transient behaviors of the fuorescence time course showed exponential increases in the rate of O^(·-)_(2) production in the presence of the ETC uncoupler or inhibitors.The most dramatic and the fastest increase in O^(·-)_(2)production was observed when the cells were treated with the uncoupling agent,PCP.We also showed that only the complex IV inhibitor,KCN,attenuated the marked surge in O^(·-)_(2)production induced by PCP.The results showed that mitochondrial respiratory complexes I,III and IV are sources of O^(·-)_(2) production in PAECs,and a new observation that ROS production during uncoupling of mitochondrial res-piration is mediated in part via complex IV.This novel method can be applied in other studies that examine ROS production under stress condition and during ROS mediated injuries in vritro.
