Design, Synthesis and Biological Evaluation of Jahanyne Analogs as Cell Cycle Arrest Inducers
Baijun Ye,
Jianmiao Gong,
Qiuying Li,
Shiqi Bao,
Xuemei Zhang,
Jing Chen,
Qing Meng,
Bolin Chen,
Peng Jiang,
Liang Wang,
Yue Chen
Affiliations
Baijun Ye
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
Jianmiao Gong
Accendatech Co., Ltd., Tianjin 300384, China
Qiuying Li
Accendatech Co., Ltd., Tianjin 300384, China
Shiqi Bao
Accendatech Co., Ltd., Tianjin 300384, China
Xuemei Zhang
Accendatech Co., Ltd., Tianjin 300384, China
Jing Chen
Accendatech Co., Ltd., Tianjin 300384, China
Qing Meng
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
Bolin Chen
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
Peng Jiang
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
Liang Wang
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
Yue Chen
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
Jahanyne, a lipopeptide with a unique terminal alkynyl and OEP (2-(1-oxo-ethyl)-pyrrolidine) moiety, exhibits anticancer activity. We synthesized jahanyne and analogs modified at the OEP moiety, employing an α-fluoromethyl ketone (FMK) strategy. Preliminary bioassays indicated that compound 1b (FMK−jahanyne) exhibited decreased activities to varying degrees against most of the cancer cells tested, whereas the introduction of a fluorine atom to the α-position of a hydroxyl group (2b) enhanced activities against all lung cancer cells. Moreover, jahanyne and 2b could induce G0/G1 cell cycle arrest in a concentration-dependent manner.