Dimethyl 2,2′-[2,2′-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect
Yaonan Wang,1,2 Haiyan Chen,1,2 Xiaoyi Zhang,1,2 Lin Gui,1,2 Jianhui Wu,1,2 Qiqi Feng,1,2 Shiqi Peng,1,2 Ming Zhao1–3 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; 2Engineering Res...
Guardado en:
| Autores principales: | , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2018
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/0ddb1f116b99477abe08e40f69653bc5 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:0ddb1f116b99477abe08e40f69653bc5 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:0ddb1f116b99477abe08e40f69653bc52021-12-02T05:39:32ZDimethyl 2,2′-[2,2′-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect1178-2013https://doaj.org/article/0ddb1f116b99477abe08e40f69653bc52018-11-01T00:00:00Zhttps://www.dovepress.com/dimethyl-22prime-22prime-ethane-11-diylbis1h-indole-32-diyl-diacetate--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yaonan Wang,1,2 Haiyan Chen,1,2 Xiaoyi Zhang,1,2 Lin Gui,1,2 Jianhui Wu,1,2 Qiqi Feng,1,2 Shiqi Peng,1,2 Ming Zhao1–3 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; 3Beijing Laboratory of Biomedical Materials, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China Background: Due to the discovery that deep venous thrombosis (DVT) inhibitor is of chemotherapeutic importance, the nano-property of dimethyl 2,2'-[2,2'-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate (DEBIC), a recently reported antitumor agent, is worthy of characterization.Materials and methods: One-pot reaction was used to prepare DEBIC. Electrospray Ionization (+/-)-Fourier Transform-Ion Cyclotron Resonance-Mass Spectrometer (ESI(+/-)-FT-ICR-MS), quadrupole Collision Induced Dissociation (qCID) and nuclear overhauser effect spectroscopy spectra were used to present the assembly of DEBIC. Transmission electron microscopy, scanning electron microscopy, atomic force microscopy and Faraday–Tyndall effect were used to visualize the nano-property of DEBIC. Rat models were used to evaluate DVT inhibition and the bleeding reaction of DEBIC.Results: One-pot reaction can provide DEBIC in acceptable yield and high purity. In water, rat plasma and lyophilized powders of DEBIC existed as particles of small nano-size. In vivo DEBIC inhibited DVT in a dose-dependent manner. The minimal effective dose of DEBIC was 1.7 µmol/kg. Even the dose of 36 µmol/kg/day DEBIC did not induce bleeding side effect in DVT rats like in warfarin (0.82 µmol/kg/day).Conclusion: DEBIC is a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect. Keywords: nano-property, DVT inhibition, bleeding-reaction, tumor, thrombosisWang YChen HZhang XGui LWu JFeng QPeng SZhao MDove Medical PressarticleNano-propertyDVT-inhibitionBleeding-reaction.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 7835-7844 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Nano-property DVT-inhibition Bleeding-reaction. Medicine (General) R5-920 |
| spellingShingle |
Nano-property DVT-inhibition Bleeding-reaction. Medicine (General) R5-920 Wang Y Chen H Zhang X Gui L Wu J Feng Q Peng S Zhao M Dimethyl 2,2′-[2,2′-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect |
| description |
Yaonan Wang,1,2 Haiyan Chen,1,2 Xiaoyi Zhang,1,2 Lin Gui,1,2 Jianhui Wu,1,2 Qiqi Feng,1,2 Shiqi Peng,1,2 Ming Zhao1–3 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; 3Beijing Laboratory of Biomedical Materials, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China Background: Due to the discovery that deep venous thrombosis (DVT) inhibitor is of chemotherapeutic importance, the nano-property of dimethyl 2,2'-[2,2'-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate (DEBIC), a recently reported antitumor agent, is worthy of characterization.Materials and methods: One-pot reaction was used to prepare DEBIC. Electrospray Ionization (+/-)-Fourier Transform-Ion Cyclotron Resonance-Mass Spectrometer (ESI(+/-)-FT-ICR-MS), quadrupole Collision Induced Dissociation (qCID) and nuclear overhauser effect spectroscopy spectra were used to present the assembly of DEBIC. Transmission electron microscopy, scanning electron microscopy, atomic force microscopy and Faraday–Tyndall effect were used to visualize the nano-property of DEBIC. Rat models were used to evaluate DVT inhibition and the bleeding reaction of DEBIC.Results: One-pot reaction can provide DEBIC in acceptable yield and high purity. In water, rat plasma and lyophilized powders of DEBIC existed as particles of small nano-size. In vivo DEBIC inhibited DVT in a dose-dependent manner. The minimal effective dose of DEBIC was 1.7 µmol/kg. Even the dose of 36 µmol/kg/day DEBIC did not induce bleeding side effect in DVT rats like in warfarin (0.82 µmol/kg/day).Conclusion: DEBIC is a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect. Keywords: nano-property, DVT inhibition, bleeding-reaction, tumor, thrombosis |
| format |
article |
| author |
Wang Y Chen H Zhang X Gui L Wu J Feng Q Peng S Zhao M |
| author_facet |
Wang Y Chen H Zhang X Gui L Wu J Feng Q Peng S Zhao M |
| author_sort |
Wang Y |
| title |
Dimethyl 2,2′-[2,2′-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect |
| title_short |
Dimethyl 2,2′-[2,2′-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect |
| title_full |
Dimethyl 2,2′-[2,2′-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect |
| title_fullStr |
Dimethyl 2,2′-[2,2′-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect |
| title_full_unstemmed |
Dimethyl 2,2′-[2,2′-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect |
| title_sort |
dimethyl 2,2′-[2,2′-(ethane-1,1-diyl)bis(1h-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect |
| publisher |
Dove Medical Press |
| publishDate |
2018 |
| url |
https://doaj.org/article/0ddb1f116b99477abe08e40f69653bc5 |
| work_keys_str_mv |
AT wangy dimethyl22prime22primeethane11diylbis1hindole32diyldiacetateasmallmoleculecapableofnanoscaleassemblyinhibitingvenousthrombosisandinducingnobleedingsideeffect AT chenh dimethyl22prime22primeethane11diylbis1hindole32diyldiacetateasmallmoleculecapableofnanoscaleassemblyinhibitingvenousthrombosisandinducingnobleedingsideeffect AT zhangx dimethyl22prime22primeethane11diylbis1hindole32diyldiacetateasmallmoleculecapableofnanoscaleassemblyinhibitingvenousthrombosisandinducingnobleedingsideeffect AT guil dimethyl22prime22primeethane11diylbis1hindole32diyldiacetateasmallmoleculecapableofnanoscaleassemblyinhibitingvenousthrombosisandinducingnobleedingsideeffect AT wuj dimethyl22prime22primeethane11diylbis1hindole32diyldiacetateasmallmoleculecapableofnanoscaleassemblyinhibitingvenousthrombosisandinducingnobleedingsideeffect AT fengq dimethyl22prime22primeethane11diylbis1hindole32diyldiacetateasmallmoleculecapableofnanoscaleassemblyinhibitingvenousthrombosisandinducingnobleedingsideeffect AT pengs dimethyl22prime22primeethane11diylbis1hindole32diyldiacetateasmallmoleculecapableofnanoscaleassemblyinhibitingvenousthrombosisandinducingnobleedingsideeffect AT zhaom dimethyl22prime22primeethane11diylbis1hindole32diyldiacetateasmallmoleculecapableofnanoscaleassemblyinhibitingvenousthrombosisandinducingnobleedingsideeffect |
| _version_ |
1718400276036059136 |