Abstract
Thirty etopside esters of malic acid were synthesized and have been shown to exhibit improved aqueous solubility and stability in neutral solution except for compounds 7Ia-c and 9Ia-c. Compounds 6Ia-c, 6IIb-c, 8Ia-b and 10Ib have been shown to function as prodrugs, whereas the other synthesized derivatives were too stable to reveal parent drugs in vivo. Among synthesized compounds, 8Ib, 4'-O-demethyl 4'-L-malyl epipodophyllotoxins showed the most potent anticancer activity and favorable stability in vitro.
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