Water-soluble derivatives of 25-OCH₃-PPD and their anti-proliferative activities

(20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH₃-PPD, AD-1) is a dammarane-type sapogenin showing anti-tumor potential. In the search for new anti-tumor agents with higher potency than our previously identified compound 25-OCH₃-PPD, 11 novel sulfamic acid and diacid derivatives that could improve water solubility and contribute to good drug potency and pharmacokinetic profiles were designed and synthesized. Their in vitro anti-tumor activities in MCF-7, A-549, HCT-116, and BGC-823 cell lines and one normal cell line were tested by standard MTT assay. Results showed that compared with compound 25-OCH₃-PPD, compounds 1, 4, and 5 exhibited higher cytotoxic activity on almost all cell lines, together with lower toxicity in the normal cell. In particular, compound 1 exhibited the best anti-tumor activity in the in vitro assays. The water solubility of 25-OCH₃-PPD and its derivatives was tested and the results showed that the solubility of 25-OCH₃-PPD sulfamic acid and diacid derivatives were better than that of 25-OCH₃-PPD in water, which may provide valuable data for the research and development of new anti-tumor agents.