Syntheses of 3 ketolanosterol, 3 acetolanosterol, 3 oximolanosterol, 3α and 3β aminolanosterol were described The products have been fully characterized on the basis of their chromatographic (TLC R f, GLC R...Syntheses of 3 ketolanosterol, 3 acetolanosterol, 3 oximolanosterol, 3α and 3β aminolanosterol were described The products have been fully characterized on the basis of their chromatographic (TLC R f, GLC RRTc) and spectral (IR, MS, 1 H NMR, 13 C NMR) properties展开更多
Novel tetralin compounds were designed and synthesized on the three-dimensional model of lanosterol 14α-demethylase of Candida albicans. All of the lead compounds exhibited potent antifungal activities, especially co...Novel tetralin compounds were designed and synthesized on the three-dimensional model of lanosterol 14α-demethylase of Candida albicans. All of the lead compounds exhibited potent antifungal activities, especially compounds 16, 20. The mode of the action of the lead compounds was different from that of azoles. The present study affords the possibility to develop novel antifungal agents that specifically interact with the amino acid residues in the active site and avoid the serious toxicity arising from coordination binding with the heme of mammalian P450s.展开更多
Background:To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.Methods:Nine elder cynomolgus monkeys were used,consisting of three monkeys without...Background:To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.Methods:Nine elder cynomolgus monkeys were used,consisting of three monkeys without cataract as controls,three monkeys with naturally occurring cortical cataract,and three monkeys with nuclear cataract as intervention groups.Nanoparticulated thermogel with lanosterol and fluorescein was administered by subconjunctival injection in the monkeys with cataract.Fluorescence changes of injected thermogel and cataract progression were observed.Lanosterol concentration in aqueous humor,solubility changes in lens proteins,and oxidative stress levels were analyzed in the lenses of the control and intervention groups.Results:Injected thermogel showed decreased fluorescence during follow up.Lanosterol concentration in aqueous humor increased in the first 2 weeks and then gradually decreased,which was in accordance with the changes in cortical lens clarity.However,lenses with nuclear opacification showed little change.In the cortical region of lenses with cortical cataract,solubility ofα-crystallin was significantly increased after administration of lanosterol,as well as the reduction of oxidative stress.Conclusions:We demonstrated the effect of lanosterol on cataract progression based on in vivo models of primates.Lanosterol showed a short-term and reliable reversal effect on reducing cataract severity in cortical cataract in the early stages,possibly due to the increase in the solubility of lens proteins and changes in the oxidative stress status.Lanosterol administration using subconjunctival drug release system could be a promising nonsurgical approach for future clinical studies of cataract prevention and treatment.展开更多
文摘Syntheses of 3 ketolanosterol, 3 acetolanosterol, 3 oximolanosterol, 3α and 3β aminolanosterol were described The products have been fully characterized on the basis of their chromatographic (TLC R f, GLC RRTc) and spectral (IR, MS, 1 H NMR, 13 C NMR) properties
基金supported by the National Natural Science Foundation of China(No.30572257)
文摘Novel tetralin compounds were designed and synthesized on the three-dimensional model of lanosterol 14α-demethylase of Candida albicans. All of the lead compounds exhibited potent antifungal activities, especially compounds 16, 20. The mode of the action of the lead compounds was different from that of azoles. The present study affords the possibility to develop novel antifungal agents that specifically interact with the amino acid residues in the active site and avoid the serious toxicity arising from coordination binding with the heme of mammalian P450s.
基金funded by research grants from the National Natural Science Foundation of China(Grants No.82122017,81870642,81970780,81670835,and 81700819)Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission(Grants No.19441900700 and 21S31904900)Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center(Grants No.SHDC12019X08 and SHDC2020CR4078)。
文摘Background:To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.Methods:Nine elder cynomolgus monkeys were used,consisting of three monkeys without cataract as controls,three monkeys with naturally occurring cortical cataract,and three monkeys with nuclear cataract as intervention groups.Nanoparticulated thermogel with lanosterol and fluorescein was administered by subconjunctival injection in the monkeys with cataract.Fluorescence changes of injected thermogel and cataract progression were observed.Lanosterol concentration in aqueous humor,solubility changes in lens proteins,and oxidative stress levels were analyzed in the lenses of the control and intervention groups.Results:Injected thermogel showed decreased fluorescence during follow up.Lanosterol concentration in aqueous humor increased in the first 2 weeks and then gradually decreased,which was in accordance with the changes in cortical lens clarity.However,lenses with nuclear opacification showed little change.In the cortical region of lenses with cortical cataract,solubility ofα-crystallin was significantly increased after administration of lanosterol,as well as the reduction of oxidative stress.Conclusions:We demonstrated the effect of lanosterol on cataract progression based on in vivo models of primates.Lanosterol showed a short-term and reliable reversal effect on reducing cataract severity in cortical cataract in the early stages,possibly due to the increase in the solubility of lens proteins and changes in the oxidative stress status.Lanosterol administration using subconjunctival drug release system could be a promising nonsurgical approach for future clinical studies of cataract prevention and treatment.
