title: The derivatives of Pulsatilla saponin A, a bioactive compound from Pulsatilla chinensis: Their synthesis, cytotoxicity, haemolytic toxicity and mechanism of action.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Tong
authors.affiliation: Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, 80 Chang Jiang Road, Nanyang 473000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Duan
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang, 56 Yang Ming Road, Nanchang 330006, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang, 56 Yang Ming Road, Nanchang 330006, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Feng
authors.affiliation: College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, China. Electronic address: chinacczz0720@gmail.com.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Shilin
authors.initials: S
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D031946:Pulsatilla / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D012503:Saponins; C000588664:Pulsatilla saponin A
keywords: Cell cycle arrest; Cytotoxicity; Haemolytic activity; Pulsatilla saponin A; Structure–activity relationship (SAR)