Modular assembly of cytotoxic acetogenin mimetics by click linkage with nitrogen functionalities

Linear annonaceous acetogenin mimetic AA005 has been found to exhibit potent antitumor activity and significant selectivity between human normal and cancerous cells. Utilizing the concept of Click chemistry, a convergent modular fragment-assembly approach has been newly developed and successfully applied to the synthesis of three representative AA005-like molecules via formation of small nitrogen-containing heterocycles or amide bond. These nitrogen-containing analogues were found to exhibit low micromolar inhibitory activities against the growth of several cancer cell lines.