Solid-Phase Library Synthesis of Bi-Functional Derivatives
of Oleanolic and Maslinic Acids and Their Cytotoxicity on Three Cancer
Cell Lines
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Abstract
A wide
set of 264 compounds has been semisynthesized with high
yields and purities. These compounds have been obtained through easy
synthetic processes based on a solid-phase combinatorial methodology.
All the members of this library have one central core of a natural
pentacyclic triterpene (oleanolic or maslinic acid) and differ by
6 amino acids, coupled with the carboxyl group at C-28 of the triterpenoid
skeleton, and by 10 different acyl groups attached to the hydroxyl
groups of the A-ring of these molecules. According to the literature
on the outstanding and promising pharmacological activities of other
similar terpene derivatives, some of these compounds have been tested
for their cytotoxic effects on the proliferation of three cancer cell
lines: B16–F10, HT29, and Hep G2. In general, we have found
that around 70% of the compounds tested show cytotoxicity in all three
of the cell lines selected; around 60% of the cytotoxic compounds
are more effective than their corresponding precursors, that is, oleanolic
(OA) or maslinic (MA) acids; and nearly 50% of the cytotoxic derivatives
have IC<sub>50</sub> values between 2- to 320-fold lower than their
corresponding precursor (OA or MA)