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.

Eleven novel 25-OCH3-PPD derivatives were synthesized and their in vitro anti-tumor activities were tested by standard MTT assay via MCF-7, A-549, HCT-116, and BGC-823 cell lines. Results suggest that most of the sulfamic acid derivatives of 25-OCH3-PPD were favorable for anti-tumor activity compared with 25-OCH3-PPD. The most promising compounds in this series of synthetic compounds were 1, 4, and 5, which showed good activities against all cell lines and were to act as good anticancer agents with high efficiency and low toxicity. In particular, compound 1 exhibited the strongest growth inhibition activity in in vitro assays. The water solubility of 25-OCH3-PPD and its sulfamic acid and diacid 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.94