Design, synthesis and structure-activity relationships of mangostin analogs as cytotoxic agents

In order to better understand the structure-activity relationship of mangostin, a series of xanthone derivatives based on α-mangostin were designed and synthesized. All the compounds were evaluated for their cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) using MTT assays. Most of them showed cytotoxicity and most of all, compounds 1a and 2h showed the highest cytotoxic potency by HL-60 cancer cell lines with IC 50 values of 5.96 μM and 6.90 μM respectively; compound 3e showed the highest cytotoxic potency against SMMC-7221 cancer cell line with IC 50 values of 3.98 μM; compounds 2e and 2m showed lower cytotoxicity but higher selectivity than α-mangostin against HL-60 and SMMC-7221 cancer cell lines respectively. Structure-activity relationship analysis indicates that the maintenance of the isopentene group at C-8 is essential for the cytotoxic activity. A series xanthone derivatives were synthesized and cytotoxicity results indicated that the isopentene group at C-8 is essential.