This paper reports a continous study of the use of short chain peptides as carriers of a potential antitumor agents: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug...This paper reports a continous study of the use of short chain peptides as carriers of a potential antitumor agents: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we synthesized another two new DMQ-MA-peptide-chlorambucil (CRB) derivatives: DMQ-MA-Lys(CRB)-Arg-OMe, DMQ-MA-Lys(DMQ-MA)Lys(CRB)-Arg-OMe. These peptide-chlorambucil conjugates were synthesized by coupling protected amino acids in solution and the next conjugation was achieved by reacting with pentafluorophenyl ester of DMQ-MA in DMF. The CRB in side chain was coupled by deblocking the lysyl-carbobenzyloxy protecting group Z and then reacting with the pentafluorophenyl ester of chlorambucil (CRB). Further study on cytotoxicity, DNA binding, and sequence specificity of DNA alkylation of these two new conjugates are investigating.展开更多
The present work aimed to develop and evaluate a colloidal system composed of poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) associated with chlorambucil (CHB) and its effects on cancer cells. The nanoparti...The present work aimed to develop and evaluate a colloidal system composed of poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) associated with chlorambucil (CHB) and its effects on cancer cells. The nanoparticles showed %EE (>92%), a mean particle size in the range of 240 to 334 nm and zeta potential of -16.7 to -26.0 mV. In vitro release profile showed a biphasic pattern, with an initial burst for all formulations. The scanning electron microscopy of CHB-nanoparticles showed regular spherical shapes, smooth surface without aggregations. Differential scanning calorimetry thermograms, UV-vis absorption, fluorescence emission and Fourier transform infrared spectroscopy were performed showing the entrapment of the antitumoral in drug delivery system. CHB encapsulated in PLGA nanoparticles decrease the survival rates of the breast cancer cells: 68.9% reduction of cell viability on MCF-7 cell line and 59.7% on NIH3T3. Our results indicated that polymeric nanoparticles produced by classical methods are efficient drug delivery systems for CHB.展开更多
In order to improve the antitumor activity and reduce the toxicity of the alkylating agent chlorambucil, a series of spiropiperazinium salts of chlorambucil （8） were designed and synthesized. It was found that compo...In order to improve the antitumor activity and reduce the toxicity of the alkylating agent chlorambucil, a series of spiropiperazinium salts of chlorambucil （8） were designed and synthesized. It was found that compound 8f exhibited potential in vivo activity against H22.展开更多
Carboxylesterase,a necessary enzyme in various mammalian cells,has been employed in various biological applications.Herein,we designed and synthesized a novel carboxylesterase-based prodrug,which can realize simultane...Carboxylesterase,a necessary enzyme in various mammalian cells,has been employed in various biological applications.Herein,we designed and synthesized a novel carboxylesterase-based prodrug,which can realize simultaneous drug-release imaging and cancer chemotherapy.This prodrug comprises three parts：coumarin as the fluorophore and the cleavable architecture,chlorambucil as the anticancer drug,and acetyl group as the enzyme-responsive unit.The presence of carboxylesterase leads to the activation of coumarin fluorescence,and this fluorescence serves as the reporting signal for assessing the enzyme level and drug release.Moreover,the prodrug was incorporated in liposome for monitoring drug release and chemotherapeutic effect in living cells.Upon internalization by HeLa cells,the prodrug can release chlorambucil and exhibit high cytotoxicity.This approach may provide some helpful insights for enhancing therapeutic effect and tracking the release of prodrug.展开更多
基金Provincial Natural Foundation of Shanxi Province.
文摘This paper reports a continous study of the use of short chain peptides as carriers of a potential antitumor agents: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we synthesized another two new DMQ-MA-peptide-chlorambucil (CRB) derivatives: DMQ-MA-Lys(CRB)-Arg-OMe, DMQ-MA-Lys(DMQ-MA)Lys(CRB)-Arg-OMe. These peptide-chlorambucil conjugates were synthesized by coupling protected amino acids in solution and the next conjugation was achieved by reacting with pentafluorophenyl ester of DMQ-MA in DMF. The CRB in side chain was coupled by deblocking the lysyl-carbobenzyloxy protecting group Z and then reacting with the pentafluorophenyl ester of chlorambucil (CRB). Further study on cytotoxicity, DNA binding, and sequence specificity of DNA alkylation of these two new conjugates are investigating.
文摘The present work aimed to develop and evaluate a colloidal system composed of poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) associated with chlorambucil (CHB) and its effects on cancer cells. The nanoparticles showed %EE (>92%), a mean particle size in the range of 240 to 334 nm and zeta potential of -16.7 to -26.0 mV. In vitro release profile showed a biphasic pattern, with an initial burst for all formulations. The scanning electron microscopy of CHB-nanoparticles showed regular spherical shapes, smooth surface without aggregations. Differential scanning calorimetry thermograms, UV-vis absorption, fluorescence emission and Fourier transform infrared spectroscopy were performed showing the entrapment of the antitumoral in drug delivery system. CHB encapsulated in PLGA nanoparticles decrease the survival rates of the breast cancer cells: 68.9% reduction of cell viability on MCF-7 cell line and 59.7% on NIH3T3. Our results indicated that polymeric nanoparticles produced by classical methods are efficient drug delivery systems for CHB.
基金National Natural Science Foundation of China (Grant No.20472008)Fund for Young Teachers of School of Pharmaceutical Sciences,Peking University
文摘In order to improve the antitumor activity and reduce the toxicity of the alkylating agent chlorambucil, a series of spiropiperazinium salts of chlorambucil （8） were designed and synthesized. It was found that compound 8f exhibited potential in vivo activity against H22.
基金financial support by the Science and Technology Planning Project of Guangzhou(No.201607020015)the Science and Technology Planning Project of Guangdong Province(No.2014A010105009)
文摘Carboxylesterase,a necessary enzyme in various mammalian cells,has been employed in various biological applications.Herein,we designed and synthesized a novel carboxylesterase-based prodrug,which can realize simultaneous drug-release imaging and cancer chemotherapy.This prodrug comprises three parts：coumarin as the fluorophore and the cleavable architecture,chlorambucil as the anticancer drug,and acetyl group as the enzyme-responsive unit.The presence of carboxylesterase leads to the activation of coumarin fluorescence,and this fluorescence serves as the reporting signal for assessing the enzyme level and drug release.Moreover,the prodrug was incorporated in liposome for monitoring drug release and chemotherapeutic effect in living cells.Upon internalization by HeLa cells,the prodrug can release chlorambucil and exhibit high cytotoxicity.This approach may provide some helpful insights for enhancing therapeutic effect and tracking the release of prodrug.
