The synthesis and bioevaluation of the dicyclic arene-homospermidine conjugates

Four novel dicyelic arene-homospermidine conjugates (6a-d) were synthesized and evaluated for cytotoxicity in L1210,α- difluoromethylomithine (DFMO) treated L1210,melanoma B16,spermidine (SPD) treated B16,and Hela cells.In the DFMO- treated L1210 experiments,6a-d were more sensitive to DFMO than naphthalene-homospermidine (6e),suggesting that 6a-d can utilize the polyamine transporter (PAT) to enter the cells as well as 6e.The diminished cytotoxicity in the SPD/B16 experiments also supported this conclusion.In summary,the homospermidine is an efficacious vector to ferry dicyclic arches into cells via PAT.