title: Synthesis of novel 25-hydroxyprotopanaxadiol derivatives by methylation and methoxycarbonylation using dimethyl carbonate as a environment-friendly reagent and their anti-tumor evaluation.
abstract: A previous study involving 25-hydroxyprotopanaxadiol (25-OH-PPD) illustrated that the anti-cancer activity increased by 1-3 times after C-3/C-12-OH was substituted by short-chain fatty acids. In addition, 25-OCH3-PPD was also one of our research interests; the unique difference in structure between 25-OH-PPD and 25-OCH3-PPD is that in C-25, the latter activity was 2-5 times higher than that of 25-OH-PPD. These data serves as the scientific basis of our continuing research. To further confirm the effect of short chain acylated and methylated products on the activity and to identify more potent, higher selectivity compounds, we modified 25-OH-PPD with a green environment-friendly and non-toxic chemical dimethyl carbonate (DMC), which plays the role of both solvent and reagent. This experiment yielded 14 derivatives. Their in vitro anti-tumor activities were tested on two different human tumor cell lines (HeLa and DU145) and one normal cell line (IOSE144) by standard MTT assay. The results showed that compounds 3, 5, 6, 10, 11, 12, and 13 exhibited higher cytotoxic activity on two cell lines, with IC50 values within the range of 1.1-12μM. Compounds 12 and 13 exhibited the highest potent activity, with IC50 values of 1.1 and 1.2μM, respectively, on HeLa cells. Antitumor activity significantly increased after the hydroxyl groups are substituted by methyl. The results of the present study may provide useful data for evaluating the structure-activity relationships of other dammarane-type sapogenins and developing new antitumor agents.
authors: School 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.
authors: Junhui
authors: J
authors: Guo
authors: School 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.
authors: Zhe
authors: Z
authors: Xu
authors: School 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.
authors: Yafei
authors: Y
authors: Liu
authors: School 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.
authors: Xude
authors: X
authors: Wang
authors: School 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.
authors: Yuqing
authors: Y
authors: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D005561:Formates / Q000737:chemistry*; D036145:Ginsenosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry; D020128:Inhibitory Concentration 50
chemical_list: C529607:25-hydroxyprotopanaxadiol; D000970:Antineoplastic Agents; D005561:Formates; D036145:Ginsenosides; D007202:Indicators and Reagents; C023025:methyl carbonate
keywords: 25-Hydroxyprotopanaxadiol; Anti-tumor activity; Derivatives; Dimethyl carbonate