In the field of drug delivery, controllability of drug release site and duration are among the most important factors to manipulate the drug efficacy and side effects. In this paper, a series of nano-prodrugs (NPs) composed of anticancer agent SN-38 and various substituent groups were synthesized and fabricated. By increasing the hydrophobicity of the prodrug molecule (calculated logP values exceeded ca. 7) through changing the substituent group, the hydrolysis susceptibility of SN-38 NPs in mouse serum was drastically decreased, thus prolonged the blood retention time of the NPs. In light of this knowledge and the dispersion stability in aqueous media, SN-38 NP modified with cholesterol (SN-38-chol NPs) was selected to be the optimal candidate among the screened NPs. The in vivo pharmacological effect of SN-38-chol NP was about 10 times higher than irinotecan, the clinically used solubilized prodrug analog of SN-38. In addition, SN-38-chol NP has low side effects in evaluating intestinal damage. These NPs possess great potential for clinical application and promise to be a next-generation of drug for cancer treatment.
Enone compounds are well-known as useful building blocks that can be converted into a variety of valuable compounds. This study describes a synthetic method to synthesize Eselective or multi-substituted enones by an Ir-catalyzed cascade reaction under reducing conditions. We found that the cascade reaction, including reduction/isomerization/dehydration, pro-ceeds by treating bis-allyl alcohol with Crabtree's catalyst in a hydrogen atmosphere, which forms the desired product with high diastereoselectivity. We investigated acceptable catalysts to the reaction and the synthesis of enone using di-, tri-and tetrasubstituted olefin substrates. Additionally, the given results suggested a hypothesis of reaction mechanism.
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