A new approach for asymmetric synthesis of alkannin and shikonin is presented. The chiral centers of the targets were introduced via an asymmetric C-arylation of protected chiral glyceraldehyde in high de. The two e...A new approach for asymmetric synthesis of alkannin and shikonin is presented. The chiral centers of the targets were introduced via an asymmetric C-arylation of protected chiral glyceraldehyde in high de. The two enantiomers were prepared with the D-isopropylidenegly- ceraldehyde as the starting material.展开更多
DMAKO-05,a novel dimethylation of alkannin oxime derivative,exhibits remarkable anticancer activity as well as excellent cellular selectivity and thus has been considered as a promising antineoplastic agent for colore...DMAKO-05,a novel dimethylation of alkannin oxime derivative,exhibits remarkable anticancer activity as well as excellent cellular selectivity and thus has been considered as a promising antineoplastic agent for colorectal carcinoma and melanoma.However,its potent cytotoxicity is not closely associated with reactive oxygen species（ROS） and bioreductive alkylation.Its specific antitumor target（s） has still remained elusive.To recognize the molecular target（s） of DMAKO-05 and its analogs,four biotinylated DMAKO derivatives were designed and prepared.The biotin moiety was successfully introduced in the molecule through a modified Mitsunobu reaction,which kept its anticancer activity.Moreover,the cellbased investigation demonstrated that replacement of the linker C4 chain with another alkyl chain（C6 or C8） gave rise to the enhancement of cytotoxicity.Among these biotinyl derivatives,both compound 16 and 8c exhibited more potent anticancer activity than DMAKO-05 against MCF-7 cells and were comparatively effective to alkannin toward HCT-15 cells.As expected,they might be thought as ideal chemical probes.Collectively,our present work could provide an available approach for the identification of the potential antineoplastic target（s） of DMAKO derivatives.展开更多
Alkannin/shikonin(A/S)and their derivatives are naturally occurring naphthoquinones majorly found in Boraginaceae family plants.They are integral constituents of traditional Chinese medicine Zicao(roots of Lithospermu...Alkannin/shikonin(A/S)and their derivatives are naturally occurring naphthoquinones majorly found in Boraginaceae family plants.They are integral constituents of traditional Chinese medicine Zicao(roots of Lithospermum erythrorhizon).In last two decades significant increase in pharmacological investigations on alkannin/shikonin and their derivatives has been reported that resulted in discovery of their novel mechanisms in various diseases and disorders.This review throws light on recently conducted pharmacological investigations on alkannin/shikonin and their derivatives and their outputs.Various analytical aspects are also discussed and brief summary of patent applications on inventions containing alkannin/shikonin and its derivatives is also provided.展开更多
The aim of this study was to investigate the potential of novel electrospun fiber mats loaded with alkannin and shikonin(A/S)derivatives,using as carrier a highly biocompatible,bio-derived,ecofriendly polymer such as ...The aim of this study was to investigate the potential of novel electrospun fiber mats loaded with alkannin and shikonin(A/S)derivatives,using as carrier a highly biocompatible,bio-derived,ecofriendly polymer such as poly[(R)-3-hydroxybutyric acid](PHB).PHB fibers containing a mixture of A/S derivatives at different ratios were successfully fabricated via electrospinning.As evidenced by scanning electron microscopy,the fibers formed a bead-free mesh with average diameters from 1.25 to 1.47 lm.Spectroscopic measurements suggest that electrospinning marginally increases the amorphous content of the predominantly crystalline PHB in the fibers,while a significant drug amount lies near the fiber surface for samples of high total A/S content.All scaffolds displayed satisfactory characteristics,with the lower concentrations of A/S mixture-loaded PHB fiber mats achieving higher porosity,water uptake ratios,and entrapment efficiencies.The in vitro dissolution studies revealed that all samples released more than 70%of the encapsulated drug after 72 h.All PHB scaffolds tested by cell viability assay were proven non-toxic for Hs27 fibroblasts,with the 0.15 wt.%sample favoring cell attachment,spreading onto the scaffold surface,as well as cell proliferation.Finally,the antimicrobial activity of PHB meshes loaded with A/S mixture was documented for Staphylococcus epidermidis and S.aureus.展开更多
基金the National Natural Science Foundation of China[32071532]for financial supports
文摘A new approach for asymmetric synthesis of alkannin and shikonin is presented. The chiral centers of the targets were introduced via an asymmetric C-arylation of protected chiral glyceraldehyde in high de. The two enantiomers were prepared with the D-isopropylidenegly- ceraldehyde as the starting material.
基金supported by National Natural Science Foundation of China (No. 81373274)Ph.D. Programs Foundation of Ministry of Education China (No. 20120073110068)Shanghai Biomedical Supporting Funding (No. 15431900600)
文摘DMAKO-05,a novel dimethylation of alkannin oxime derivative,exhibits remarkable anticancer activity as well as excellent cellular selectivity and thus has been considered as a promising antineoplastic agent for colorectal carcinoma and melanoma.However,its potent cytotoxicity is not closely associated with reactive oxygen species（ROS） and bioreductive alkylation.Its specific antitumor target（s） has still remained elusive.To recognize the molecular target（s） of DMAKO-05 and its analogs,four biotinylated DMAKO derivatives were designed and prepared.The biotin moiety was successfully introduced in the molecule through a modified Mitsunobu reaction,which kept its anticancer activity.Moreover,the cellbased investigation demonstrated that replacement of the linker C4 chain with another alkyl chain（C6 or C8） gave rise to the enhancement of cytotoxicity.Among these biotinyl derivatives,both compound 16 and 8c exhibited more potent anticancer activity than DMAKO-05 against MCF-7 cells and were comparatively effective to alkannin toward HCT-15 cells.As expected,they might be thought as ideal chemical probes.Collectively,our present work could provide an available approach for the identification of the potential antineoplastic target（s） of DMAKO derivatives.
文摘Alkannin/shikonin(A/S)and their derivatives are naturally occurring naphthoquinones majorly found in Boraginaceae family plants.They are integral constituents of traditional Chinese medicine Zicao(roots of Lithospermum erythrorhizon).In last two decades significant increase in pharmacological investigations on alkannin/shikonin and their derivatives has been reported that resulted in discovery of their novel mechanisms in various diseases and disorders.This review throws light on recently conducted pharmacological investigations on alkannin/shikonin and their derivatives and their outputs.Various analytical aspects are also discussed and brief summary of patent applications on inventions containing alkannin/shikonin and its derivatives is also provided.
基金This work was supported by the project‘MICROMETABOLITE’that has received funding from the European Union’s Horizon 2020 research and innovation programme,under the Marie Skłodowska-Curie grant agreement[No 721635]A.S.Arampatzis,K.N.Kontogiannopoulos,A.Rat,A.Willems and A.N.Assimopoulou acknowledge support of this work from MICROMETABOLITE.
文摘The aim of this study was to investigate the potential of novel electrospun fiber mats loaded with alkannin and shikonin(A/S)derivatives,using as carrier a highly biocompatible,bio-derived,ecofriendly polymer such as poly[(R)-3-hydroxybutyric acid](PHB).PHB fibers containing a mixture of A/S derivatives at different ratios were successfully fabricated via electrospinning.As evidenced by scanning electron microscopy,the fibers formed a bead-free mesh with average diameters from 1.25 to 1.47 lm.Spectroscopic measurements suggest that electrospinning marginally increases the amorphous content of the predominantly crystalline PHB in the fibers,while a significant drug amount lies near the fiber surface for samples of high total A/S content.All scaffolds displayed satisfactory characteristics,with the lower concentrations of A/S mixture-loaded PHB fiber mats achieving higher porosity,water uptake ratios,and entrapment efficiencies.The in vitro dissolution studies revealed that all samples released more than 70%of the encapsulated drug after 72 h.All PHB scaffolds tested by cell viability assay were proven non-toxic for Hs27 fibroblasts,with the 0.15 wt.%sample favoring cell attachment,spreading onto the scaffold surface,as well as cell proliferation.Finally,the antimicrobial activity of PHB meshes loaded with A/S mixture was documented for Staphylococcus epidermidis and S.aureus.
