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.