Semi-synthesis of Cytotoxic Molecules From Cycloartane Type Sapogenols

Semi-synthetic anticancer drug-discovery programs focusing on saponins mainly engaged with commercially available triterpenoids such as oleanolic acid and ursolic acid (1,2,3), not including less common miscellaneous aglycons such as cycloartanes, lanostanes and hopanes. Cycloartanes occupy a special position among low molecular bioregulators because they are produced by photosynthesizing organisms only, and one from the initial representatives of this range, cycloartenol, serves as the key link in the biosynthesis of different phytosterols (4). In general, the plants of Astragalus genera proved to be the richest source of this class of compounds.

As part of our continuing studies on cycloartane-type sapogenols of Astragalus genus, twenty molecules were synthesized starting from cycloastragenol and its isomer astragenol, and their cyctotoxicities were tested against three different cancer cell lines (HT-29: human column cancer cell line; MDA-MB-231: human breast cancer cell line; PC-3: human prostate cancer cell line) together with a transformed cell line (HEK 293: human embryonic transformed kidney cell line). Some of the semi-synthetic derivatives such as A2 and C5 exhibited more potency compared to the starting molecules.

Further studies are in progress to prepare more potent compounds versus cancer lines.

Figure 1

	IC50 (µM)
	HT-29	MDA-MB-231	PC-3	HEK 293
AG	41.59	88.97	93.99	60.13
A2	19.62	19.26	13.71	12.14
CG	30.49	>100	>100	>100
C5	11.61	63.03	30.25	9.15

Acknowledgement: TUBITAK (109S345)

References: 1. Honda T et al. (2000)J Med Chem 43: 1866–1877.

2. Honda T et al. (1999) Bioorg Med Chem Lett 9: 3429–3434.

3. Gao X et al. (2007)J Neurooncol 84: 147–157.

4. Davis PH (1970) Flora of Turkey and East Aegean Islands Vol 4. University Press. Edinburgh.