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[Display omitted] • Structural optimizations of acridone derivatives based on E17 and E24. • Structure-activity outcome was enriched. • The most potent compound 6h is a strong topo IIa/b poison. • 6h can cause obvious DNA damage and DSBS breaks. • 6h can induce apoptosis. Previously, an array of N -substituted acridone derivatives have been reported as potent topoisomerase II (topo II) inhibitors, and preliminary structure–activity relationship (SAR) outcomes revealed that the linker between 1-NH and N -methyl piperazine motif of the tricyclic acridone scaffold significantly affected their anti-proliferative potencies. To further explore the SARs of acridone-derived topo II inhibitors, a wider range of novel acridone derivatives were herein synthesized via two rounds of structural optimizations on two validated hits, E17 and E24. Initially, the linker length was optimized, and then influences of N -methyl piperazinyl moiety and disposition of three N atoms on the bioactivity were investigated. As a result, a newly developed topo II inhibitor 6 h was found to be more potent than E17 and E24 , thereby serving as a tool compound for the follow-up mechanistic study. Compound 6 h functioned as a strong topo IIα/β inhibitor, caused obvious DNA damage, and induced apoptosis by triggering the loss of mitochondrial membrane potential (Δψ m). Further molecular docking and MD study illustrated the favorable interactions of 6 h with both topo IIα and topo IIβ subtypes. [ABSTRACT FROM AUTHOR]

Type II DNA topoisomerase (topo II) is an essential nuclear enzyme and a well-validated anticancer drug target. Previously, we have carried out several rounds of structural optimizations on our in-house topo II inhibitor E17, which was shown to have superior anticancer activity and less risk of multidrug resistance (MDR). Among the newly developed acridone derivatives, 6h displayed significant anticancer efficacy with unique mechanisms of action. At low concentrations, it arrested cancer cell cycles and triggered cell apoptosis, which is similar to the action of the well-known topo II inhibitor VP16. By contrast, 6h showed significant and long-term anti-proliferative activity at relatively high concentrations, with negligible influence on apoptosis. In addition, 6h exhibited no serious cardiotoxicity compared to doxorubicin (DOXO), a widely used topo II-targeting antineoplastic drug in clinic, but with damaging myocardial side effects. Collectively, our present work has supported the therapeutic value of 6h as a promising chemotherapy for cancers. [ABSTRACT FROM AUTHOR]

• Modified chitosan can interact with anthocyanins in a variety of ways. • Composite materials have higher encapsulation efficiency than single materials. • Many new materials have been applied to anthocyanin embedding. • The particle size of the new material is smaller than that of the traditional material. Anthocyanins are natural polyphenols belonging to the flavonoid family that possess a variety of putative health benefits when consumed in a balanced diet. However, applications of anthocyanins in, for example, functional foods are limited due to poor stability, degradation, and low transmembrane efficiency. To maintain bioactivities of anthocyanins and optimize their use, various carrier materials have been developed. Here, we reviewed the uses of the different carrier materials (organic/inorganic, micro/nano) for anthocyanin encapsulation and delivery over the past five years. The performance of different materials and interactions between anthocyanins and these materials are described. Lastly, we give our perspective on the future development trend of anthocyanin encapsulation strategies. [ABSTRACT FROM AUTHOR]