Synthesis and antitumor activity of (-)-bassianolide in MDA-MB 231 breast cancer cells through cell cycle arrest.
The high level of interest in the cyclodepsipeptides family in the natural products stems from their diverse range of biological activities. One of the cyclodepsipeptides, (-)-bassianolide, represents rich pharmacophores with diverse biological activities including potential cytotoxicity to various cancer cells. Efficient total synthesis of (-)-bassianolide was designed and achieved in nine steps, with significant improvements in the overall yield of 46.8% (vs. 7.2% yield in previous synthesis) using Ghosez's chloroenamine reagent under mild conditions. The cytotoxicity of the (-)-bassianolide was evaluated against five human tumor cells, and the results showed that the (-)-bassianolide displayed significant cytotoxicity against A549, SK-OV-3, HepG2, HCT-15, MCF-7 and MDA-MB 231 cell lines with IC50values of 7.24, 8.44, 15.39, 6.40, 11.42 and 3.98 μg/mL respectively. Specifically, (-)-bassianolide induced G0/G1 arrest associated with a decrease of cyclin A, D1 and an increase of p53, MDM2, and p21 expression in MDA-MB 231 cells. These results demonstrate that (-)-bassianolide possesses antitumor activities via arresting of the cell cycle and the synthetic approach features an efficient and mild method for the formation of amide bonds through three inter- and intramolecular coupling reactions.
Department of Chemistry, Kwangwoon University, Seoul 01897, Republic of Korea.
Bohyun
B
Mun
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Yong Joo
YJ
Park
Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea.
Gi Ho
GH
Sung
Department of Chemistry, Kwangwoon University, Seoul 01897, Republic of Korea. Electronic address: ymlee@kw.ac.kr.
Yunmi
Y
Lee
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: khkim83@skku.edu.
Ki Hyun
KH
Kim
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C035050:bassianolide
(−)-Bassianolide; Cancer; Cell cycle; MDA-MB 231; Total synthesis