The Synthesis And Biological Characteristics Of A Novel Camptothecin-artesunate Conjugate

Transferrin is a kind of targeted protein, can carry drugs in the body for transportation. And the artemisinin connect with transferrin reached disease location, spontaneously. Therefore, this work made artesunate as the carrier and linked camptothecin and artesunate together by chemical method, so that it can reduce the side effects, improve the effectiveness and bioavailability.In an attempt to improve the targeting ability, bioactivity and bioavailability of camptothecin, based on lots of references and our previous experiment, camptothecin-artesunate conjugate (C-Q) were synthesized by esterification with fast reaction ratio and high production. Investigated the inhibitory activity of the new conjugate on MCF-7 cell and SMMC-7721 by MTT experiment. The antitumor activity and drug toxicity of new conjugate was investigated in vivo of mice, and the biological characteristics of C-Q was investigated too.In the MTT assay, C-Q showed better inhibitory activity against MCF7 breast cancer cells and SMMC-7721 liver cancer cells than camptothecin or artesunate. In vivo, C-Q showed lower toxicity and better antitumour activity compared with camptothecin. Fluorescence spectroscopy showed static quenching of TF in the presence of C-Q, and thermodynamic parameters (△H> 0 and AG< 0) indicated that the reaction was spontaneous and endothermic. The main binding force between C-Q and TF was hydrophobic, as indicated by thermodynamic parameters (AH> 0 and AS> 0). Thus, synchronous fluorescence spectra showed that C-Q had no influence on the conformation of TF.Our results indicated that C-Q represents a novel potential anticancer therapeutic vector with advantages over current methods of CPT and ART administration. This novel drug delivery system allows the use of these drugs in a manner associated with few side effects for normal tissue, and which facilitates synergistic effects of anti-tumour drugs.