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.
Department of Traditional Chinese Medicine Chemical, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Wu-Xi
WX
Zhou
Department of Traditional Chinese Medicine Chemical, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Yuan-Yuan
YY
Sun
Department of Traditional Chinese Medicine Chemical, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Wei-Hui
WH
Yuan
Department of Traditional Chinese Medicine Chemical, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: zyq4885@126.com.
Yu-Qing
YQ
Zhao
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D036145:Ginsenosides / Q000737:chemistry; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D012502:Sapogenins / Q000737:chemistry; D012995:Solubility; D013451:Sulfonic Acids / Q000737:chemistry; D014315:Triterpenes / Q000737:chemistry; D014867:Water / Q000737:chemistry*; D000097669:Dammaranes
D000970:Antineoplastic Agents; D036145:Ginsenosides; D012502:Sapogenins; D013451:Sulfonic Acids; D014315:Triterpenes; D014867:Water; D000097669:Dammaranes; C005741:sulfamic acid
25-OCH(3)-PPD derivatives; Anti-tumor activities; MTT; Sulfamic acid and diacid; Water solubility