RESUMEN
A new bismuth(V) oxidative catalytic system has been developed and applied for the conversion of hydrazones into diazo compounds. With the use of low catalytic amounts of Ph3Bi and AcOH with NaBO3·H2O as a terminal oxidant, the in situ formation of Ph3Bi(OAc)2 is capable of oxidizing hydrazones in excellent yields. The reaction was applied for the synthesis of diazocarbonyls and 2,2,2-trifluoromethyl diazoalkanes in good to excellent yields.
RESUMEN
PURPOSE: The aim of this study was to introduce a smart and responsive drug carrier for Doxorubicin (DOX) and Paclitaxel (PAX) for desirable therapeutic application. METHOD: Loading and releasing of DOX and PAX from smart and pH-sensitive functionalized single-walled carbon nanotube (SWCNTs) and graphene carriers have been simulated by molecular dynamics. The influences of chitosan polymer on proposed carriers have been studied, and both carriers were functionalized with carboxyl groups to improve the loading and releasing properties of the drugs. RESULTS: The results showed that DOX could be well adsorbed on both functionalized SWCNTs and graphene. In contrast, there was a weak electrostatic and Van der Waals interaction between both these drugs and carriers at cancerous tissues, which is highly favorable for cancer therapy. Adding trimethyl chitosan (TMC) polymer to carriers facilitated DOX release at acidic tissues. Furthermore, at blood pH, the PAX loaded on the functionalized SWCNTs carrier represented the highest dispersion of the drug while the DOX-graphene showed the highest concentration of the drug at a point. In addition, the mean-square displacement (MSD) results of PAX-graphene indicated that the PAX could be adsorbed quickly and be released slowly. Finally, functionalized graphene-TMC-PAX is a smart drug system with responsive behavior and controllable drug release, which are essential in cancer therapy. CONCLUSION: Simultaneous application of the carboxyl group and TMC can optimize the pH sensitivity of the SWCNTs and graphene to prepare a novel and smart drug carrier for cancer therapy.
Asunto(s)
Quitosano/química , Portadores de Fármacos/química , Grafito/química , Nanomedicina/métodos , Nanotubos de Carbono/química , Adsorción , Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Enlace de Hidrógeno , Concentración de Iones de Hidrógeno , Paclitaxel/administración & dosificación , Electricidad EstáticaRESUMEN
The Doxorubicin (DOX) and Paclitaxel (PAX) are widely used for cancer-therapy. Herein, in the efforts devoted to developing smart drug carriers, the loading and releasing of the DOX and PAX on the pH sensitive functionalized Fullerene carrier was investigated by molecular dynamics (MD) simulations. The effects of chitosan polymer as a functionalizing agent of the Fullerene carrier was also studied. In addition, the Fullerene carrier was functionalized with carboxyl groups in order to improve the loading and releasing properties of the DOX and PAX. The results showed the DOX is well adsorbed on Fullerene which was functionalized with carboxyl group and it was released controllably in cancerous tissues. According to the results of the electrostatic and Van der Waals interactions, it was found that the functionalized Fullerene can be a proper carrier for DOX in comparison with PAX. Adding the trimethyl chitosan (TMC) polymer to the carrier could improve the Van der Waals attractions of the PAX and Fullerene which indicates that by passing the time at acidic pH, the Van der Waals energy reaches zero that leads to promote the release of the PAX in cancerous tissues. The carboxyl group which was employed as a functionalizing agent could also increase the number of hydrogen bonds for the PAX and DOX at acidic and neutral pH, respectively. Moreover, a significant rise in the number of hydrogen bonds between the PAX and Fullerene at neutral pH was achieved by adding the TMC to the carrier. A more decrease of gyration radius was obtained for the DOX at acidic pH which confirms that the DOX with TMC-Fullerene is a more stable carrier. So, this smart nanomedicine system is introduced as an promising composition for smart cancer therapy.