In continuation of our research program aimed at the development of new natural product-based anticancer agents, a series of lupeol derivatives (5a-5k and 6a-6i) were prepared with the introduction of aryl functionalities and amino acids at C-3 position. All the synthesized derivatives were assessed for in vitro anticancer activity against four human cancer cell lines using MTT assay. Interestingly, the compounds 5j, 5k, and 6g showed potent activity against MCF7 cells as compared with the parent compound. Further, the flowcytometry analysis revealed that the 5j,5k, and 6g arrest the cells at the G2/M phase and induce the early apoptosis in MCF7 cells. In addition, the selected compounds inhibit the BcL2 expression and increase the Bax protein expression in MCF7 cells. Overall, these results indicated that the lupeol derivatives could serve a promising launch point for the development as anticancer agents.