Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine
- Eur J Med Chem. 2018 Jan 1:143:1942-1958. doi: 10.1016/j.ejmech.2017.11.004.
- 1. School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
- 2. Department of Cosmetic Science, Providence University, Taichuang 433, Taiwan.
- 3. School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan; The Genomic Research Center, Academia Sinica, Taipei 128, Taiwan. Electronic address: [email protected].
A series of N-acyl, N-alkoxycarbonyl, and N-alkylcarbamoyl derivatives of 2'-deoxy-glucosyl bearing oleanolic saponins were synthesized and evaluated against HL-60, PC-3, and HT29 tumor Cancer cells. The SAR studies revealed that the activity increased in order of conjugation of 2' -amino group with carbamate > amide > urea derivatives. Lengthening the alkyl chain increased the cytotoxicity, the peak activity was found to around heptyl to nonyl substitutions. 2'-N-heptoxycarbonyl derivative 56 was found to be the most cytotoxic (IC50 = 0.76 μM) against HL-60 cells. Due to the interesting SARs of alkyl substitutions, we hypothesized that their location in the cell was different, and pursued a location study using 2'-(4″-pentynoylamino) 2'-deoxy-glucosyl OA, which suggested that these compounds distributed mainly in the cytosol.