Effect of Harmine and Its Derivatives Against Echinococcus granulosus and Comparison of DNA Damage Targets.

Cystic echinococcosis (CE) is a worldwide zoonotic disease. At present, the treatment options of CE are limited. The main drugs used in clinical chemotherapy of echinococcosis are albendazole and mebendazole, but they mainly exert longterm antiparasitic effects based on high doses. Therefore, there is an urgent need for effective and safe anti-CE drugs. Previous studies have identified harmine (HM) as a new anti-CE drug. In this study, the efficacy of harmine derivatives was evaluated in vitro and in vivo. The harmine derivatives were tested against E. granulosus protoscoleces (PSC) in vitro. The effect of harmine derivatives was time and concentration dependent at different concentrations, and the anti-CE effect was better than that of harmine. The mortality rate of PSC reached 100% on the 5th day after exposure to harmine derivatives at a concentration of 100 µmol · L -1. Compared with the untreated model control mice, the weight of the cyst was significantly reduced in infected mice treated with harmine derivatives. The effect of harmine derivatives was better than that of harmine, and there was significant difference between harmine derivatives and albendazole (P <0.001). Histopathological examination of experimental mice organs (liver, spleen, lung, brain and small intestine) showed that there was no change in the tissues except for mild inflammation in the liver. The neurotoxicity test in Caenorhabditis elegans showed that the derivative inhibited the movement, feeding, perceptual behavior and acetylcholinesterase activity of C. elegans , and its effect was lower than that of harmine. In addition, intervention with HM derivatives was preliminarily proved to cause DNA damage. This study reveals the potential of HM derivatives as a new class of anti-CE agents and indicates that Topo2a may be a promising target for the development of anti-CE drugs.

Targeted Chemotherapy for Breast Cancer Using an Intelligent Doxorubicin-Loaded Hexapeptide Hydrogel.

Self-assembling peptide hydrogels have a high water content, good biocompatibility and have become a competitive research object in the fields of tissue engineering, cancer treatment and drug delivery. In our research, a hexapeptide with high pH sensitivity was designed and synthesized by utilizing a solid-phase synthesis method. Under physiological conditions, the peptide could self-assemble into a hydrogel. When it reached the tumor acidic microenvironment, the peptide was degraded and doxorubicin was released to exert its antitumor effect. A series of physicochemical properties were investigated, including gelling ability, secondary structure, micromorphology, rheological properties and drug release studies. The results illustrated that PIDO peptide hydrogel has good pH responsiveness and injectability. In vitro cytotoxicity experiments and in vivo antitumor experiments showed that PIDO peptide hydrogel has a highly effective therapeutic effect on tumor cells and is less toxic to normal tissues. Our research provides a promising option for targeted drug delivery and sustainable release.