N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning m...N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties ε<sub>LUMO+1</sub> (one level above lowest unoccupied molecular orbital energy), d(C<sub>6</sub>-C<sub>5</sub>) (distance between C<sub>6</sub> and C<sub>5</sub> atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.展开更多
In this editorial we comment on the review by Zhou et al reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma(HCC).We focus on the immense potential of nanotechnology,particularly ligan...In this editorial we comment on the review by Zhou et al reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma(HCC).We focus on the immense potential of nanotechnology,particularly ligand-receptor mediated nanotherapy,in revolutionizing the treatment landscape of HCC.Despite advan-cements in multidisciplinary treatment,HCC remains a significant global health challenge.Ligand-mediated nanotherapy offers the opportunity for precise drug delivery to tumor sites,targeting specific receptors overexpressed in HCC cells,thereby enhancing efficacy and minimizing side effects.Overcoming drug resistance and aggressive tumor biology is facilitated by nanomedicine,bypassing traditional hurdles encountered in chemotherapy.Examples include targeting glypican-3,asialoglycoprotein,transferrin receptor or folic acid receptors,capitalizing on their over-expression in tumor cells.The ability for multi-receptor targeting through dual-ligand nanoparticle modification holds the prospect of further enhancement in specificity and efficacy of directed therapy.However,challenges including immune responses,reproducibility in nanoparticle synthesis,and production scalability remain.Future directions involve refining targeting strategies,improving drug release mechanisms,and streamlining production processes to enable personalized and multifunctional nanotherapies.Overall,the integration of nanotherapy in HCC treatment holds immense promise,but continued partnership and effort are needed in offering hope for more effective,precise,and accessible clinical care in the management of HCC.展开更多
Glioblastoma(GBM)is the most common intrinsic and aggressive primary brain tumor in adults,with a median survival of approximately 15 months.GBM heterogeneity is considered responsible for the treatment resistance and...Glioblastoma(GBM)is the most common intrinsic and aggressive primary brain tumor in adults,with a median survival of approximately 15 months.GBM heterogeneity is considered responsible for the treatment resistance and unfavorable prognosis.Proneural-mesenchymal transition(PMT)represents GBM malignant progression and recurrence,which might be a breakthrough to understand GBM heterogeneity and overcome treatment resistance.PMT is a complicated process influenced by crosstalk between GBM and tumor microenvironment,depending on intricate ligand-receptor interactions.In this review,we summarize the autocrine and paracrine pathways in the GBM microenvironment and related ligand-receptor interactions inducing PMT.We also discuss the current therapies targeting the PMT-related autocrine and paracrine pathways.Together,this review offers a comprehensive understanding of the failure of GBM-targeted therapy and ideas for future tendencies of GBM treatment.展开更多
文摘N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties ε<sub>LUMO+1</sub> (one level above lowest unoccupied molecular orbital energy), d(C<sub>6</sub>-C<sub>5</sub>) (distance between C<sub>6</sub> and C<sub>5</sub> atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.
文摘In this editorial we comment on the review by Zhou et al reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma(HCC).We focus on the immense potential of nanotechnology,particularly ligand-receptor mediated nanotherapy,in revolutionizing the treatment landscape of HCC.Despite advan-cements in multidisciplinary treatment,HCC remains a significant global health challenge.Ligand-mediated nanotherapy offers the opportunity for precise drug delivery to tumor sites,targeting specific receptors overexpressed in HCC cells,thereby enhancing efficacy and minimizing side effects.Overcoming drug resistance and aggressive tumor biology is facilitated by nanomedicine,bypassing traditional hurdles encountered in chemotherapy.Examples include targeting glypican-3,asialoglycoprotein,transferrin receptor or folic acid receptors,capitalizing on their over-expression in tumor cells.The ability for multi-receptor targeting through dual-ligand nanoparticle modification holds the prospect of further enhancement in specificity and efficacy of directed therapy.However,challenges including immune responses,reproducibility in nanoparticle synthesis,and production scalability remain.Future directions involve refining targeting strategies,improving drug release mechanisms,and streamlining production processes to enable personalized and multifunctional nanotherapies.Overall,the integration of nanotherapy in HCC treatment holds immense promise,but continued partnership and effort are needed in offering hope for more effective,precise,and accessible clinical care in the management of HCC.
基金supported by the National Natural Science Foundation of China(No.82203368)Science and Technology Projects in Guangzhou,Guangdong,China(No.202201011008)College Students'Innovative Entrepreneurial Training Plan Program,China(No.202112121201).
文摘Glioblastoma(GBM)is the most common intrinsic and aggressive primary brain tumor in adults,with a median survival of approximately 15 months.GBM heterogeneity is considered responsible for the treatment resistance and unfavorable prognosis.Proneural-mesenchymal transition(PMT)represents GBM malignant progression and recurrence,which might be a breakthrough to understand GBM heterogeneity and overcome treatment resistance.PMT is a complicated process influenced by crosstalk between GBM and tumor microenvironment,depending on intricate ligand-receptor interactions.In this review,we summarize the autocrine and paracrine pathways in the GBM microenvironment and related ligand-receptor interactions inducing PMT.We also discuss the current therapies targeting the PMT-related autocrine and paracrine pathways.Together,this review offers a comprehensive understanding of the failure of GBM-targeted therapy and ideas for future tendencies of GBM treatment.
