The derivatives of Pulsatilla saponin A, a bioactive compound from Pulsatilla chinensis: Their synthesis, cytotoxicity, haemolytic toxicity and mechanism of action
- Eur J Med Chem. 2017 Mar 31:129:325-336. doi: 10.1016/j.ejmech.2017.02.025.
- 1. College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, China; College of Pharmaceutical Science, Guizhou University, 242Hua Xi Avenue, Guiyang 550025, China.
- 2. Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, 80 Chang Jiang Road, Nanyang 473000, China.
- 3. College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
- 4. Jiangxi University of Traditional Chinese Medicine, Nanchang, 56 Yang Ming Road, Nanchang 330006, China.
- 5. College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, China. Electronic address: [email protected].
- 6. College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, China; College of Pharmaceutical Science, Guizhou University, 242Hua Xi Avenue, Guiyang 550025, China; Jiangxi University of Traditional Chinese Medicine, Nanchang, 56 Yang Ming Road, Nanchang 330006, China.
The strong haemolytic toxicity of Pulsatilla saponin A (PSA) has hampered its clinical development as an injectable Anticancer agent. To circumvent this challenge, twenty PSA derivatives with C ring or C-28 or C-3 modifications were synthesized and evaluated for cytotoxicity against seven selected human tumor lines, as well as for haemolytic toxicity. Structure-activity relationship (SAR) and structure-toxicity relationship (STR) correlations were also elucidated. Compared with PSA, compound 22 showed a better balance between haemolytic toxicity (HD50 > 500 μM) and cytotoxicity toward lung Cancer cells A549 (IC50 = 4.68 μM). Molecular studies indicated that 22 was liked to lead to G1 cell cycle arrest and therefore, 22 may be a potent antitumor drug candidate.