With the improvements in computer computing ability,data accumulation and rapid algorithm development,the integration of artificial intelligence(AI)and drug synthesis has been accelerated,significantly improving the d...With the improvements in computer computing ability,data accumulation and rapid algorithm development,the integration of artificial intelligence(AI)and drug synthesis has been accelerated,significantly improving the design and synthesis of drug molecules.Recently,data-driven computer-aided synthesis tools have been quickly and widely applied in retrosynthetic analysis,reaction prediction and automated synthesis,which can effectively accelerate the process of drug discovery and development and improve the quality of designed and synthesized drug molecules.Here,we review the development and applications of computer-aided synthesis technology and introduce recent advances in computer-aided drug development from three aspects:computer-aided drug design,computer-aided drug synthesis route design and computer-aided intelligent drug synthesis machines.Furthermore,the challenges and opportunities of computer-aided drug synthesis technology are discussed.展开更多
Enzyme prodrug therapies(EPTs)have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired t...Enzyme prodrug therapies(EPTs)have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired target site,thus achieving localized,site-specific therapeutic effect.Many effective strategies(e.g.,antibody-,viral-,gene-,as well as polymer-directed EPT)have been developed for enzyme localization to locally activate systemically administered benign prodrugs.Nevertheless,intrinsic limitations(e.g.,complex intracellular environment and catalyst instability)make the practical application of EPT strategies a task that presents itself as highly challenging.As a promising alternative to natural enzyme,nanozyme has attracted substantial attention since its discovery in 2007,mainly due to the advantages of robust catalytic activity,high stability,low cost,and facile synthesis.Recently,nanozyme-activated prodrug strategies bring a new opportunity for targeted therapy,referred to as nanozyme-activating prodrug therapies.This review focuses on recently reported nanozyme-activated prodrug strategies,aiming to provide some new insights into the potential applications in site-specific drug synthesis.展开更多
A facile,gram-scale and sustainable approach has been established for the synthesis of single-atomic-site iron on N-doped carbon(Fe_(SA)@NC-20A)via the pyrolysis of aniline modified FeZn-ZIFs,in which the synthesis of...A facile,gram-scale and sustainable approach has been established for the synthesis of single-atomic-site iron on N-doped carbon(Fe_(SA)@NC-20A)via the pyrolysis of aniline modified FeZn-ZIFs,in which the synthesis of zeolitic imidazolate frameworks(ZIFs)can be accomplished in water at room temperature,and no acid etching is required.The as-synthesized catalyst exhibits better performance on the chemoselective hydrogenation of nitroarenes with a broad substrate scope(turnover frequency(TOF)up to 1,727 h^(-1),23 examples)than most of previously reported works.Based on high-angle annular dark field scanning transmission microscopy(HAADF-STEM)images in combination with X-ray photoelectron spectroscopy(XPS),X-ray absorption spectroscopy(XAS),electron spin resonance(ESR),and Mossbauer spectroscopy,Fe is dispersed as single atoms via forming FeNx(x=4-6).This work not only determines the active sites of FesA@NC-20A for hydrogenation(FeN4),but also proposes tentative pathways for both N-H activation of hydrazine and the reduction of nitroarene on FeN4 site,both of which are the key steps for the hydrogenation of nitroarenes.In addition,this catalyst shows excellent stability,and no significant activity degradation is observed when recycling for 10 times or restoring in air for 2 months.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81922064,22177083,81874290,81803755)Sichuan University Postdoctoral Interdisciplinary Innovation Fund,and West China Nursing Discipline Development Special Fund Project,Sichuan University(No.HXHL21011).
文摘With the improvements in computer computing ability,data accumulation and rapid algorithm development,the integration of artificial intelligence(AI)and drug synthesis has been accelerated,significantly improving the design and synthesis of drug molecules.Recently,data-driven computer-aided synthesis tools have been quickly and widely applied in retrosynthetic analysis,reaction prediction and automated synthesis,which can effectively accelerate the process of drug discovery and development and improve the quality of designed and synthesized drug molecules.Here,we review the development and applications of computer-aided synthesis technology and introduce recent advances in computer-aided drug development from three aspects:computer-aided drug design,computer-aided drug synthesis route design and computer-aided intelligent drug synthesis machines.Furthermore,the challenges and opportunities of computer-aided drug synthesis technology are discussed.
基金financially supported by the Shandong Provincial Natural Science Foundation of China(No.ZR2021QC088).
文摘Enzyme prodrug therapies(EPTs)have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired target site,thus achieving localized,site-specific therapeutic effect.Many effective strategies(e.g.,antibody-,viral-,gene-,as well as polymer-directed EPT)have been developed for enzyme localization to locally activate systemically administered benign prodrugs.Nevertheless,intrinsic limitations(e.g.,complex intracellular environment and catalyst instability)make the practical application of EPT strategies a task that presents itself as highly challenging.As a promising alternative to natural enzyme,nanozyme has attracted substantial attention since its discovery in 2007,mainly due to the advantages of robust catalytic activity,high stability,low cost,and facile synthesis.Recently,nanozyme-activated prodrug strategies bring a new opportunity for targeted therapy,referred to as nanozyme-activating prodrug therapies.This review focuses on recently reported nanozyme-activated prodrug strategies,aiming to provide some new insights into the potential applications in site-specific drug synthesis.
基金the Fundamental Research Funds for the Central Universities(No.30920021120)the Key Laboratory of Biomass Energy and Material,Jiangsu Province(No.JSBEM201912)+1 种基金the National Natural Science Foundation of China(No.21905089)the Chinese Postdoctoral Science Foundation(No.2019M662775)for financial support。
文摘A facile,gram-scale and sustainable approach has been established for the synthesis of single-atomic-site iron on N-doped carbon(Fe_(SA)@NC-20A)via the pyrolysis of aniline modified FeZn-ZIFs,in which the synthesis of zeolitic imidazolate frameworks(ZIFs)can be accomplished in water at room temperature,and no acid etching is required.The as-synthesized catalyst exhibits better performance on the chemoselective hydrogenation of nitroarenes with a broad substrate scope(turnover frequency(TOF)up to 1,727 h^(-1),23 examples)than most of previously reported works.Based on high-angle annular dark field scanning transmission microscopy(HAADF-STEM)images in combination with X-ray photoelectron spectroscopy(XPS),X-ray absorption spectroscopy(XAS),electron spin resonance(ESR),and Mossbauer spectroscopy,Fe is dispersed as single atoms via forming FeNx(x=4-6).This work not only determines the active sites of FesA@NC-20A for hydrogenation(FeN4),but also proposes tentative pathways for both N-H activation of hydrazine and the reduction of nitroarene on FeN4 site,both of which are the key steps for the hydrogenation of nitroarenes.In addition,this catalyst shows excellent stability,and no significant activity degradation is observed when recycling for 10 times or restoring in air for 2 months.
