title: Synthesis and biological evaluation of sophoridinol derivatives as a novel family of potential anticancer agents.
abstract: New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 μM. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentration-time curve (AUC) of 10.3 μM·h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China.
authors.forename: Chongwen
authors.initials: C
authors.lastname: Bi
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Tang
authors.affiliation: College of Chemical Engineering, Qingdao University of Science and Technology , Qingdao 266042, China.
authors.forename: Shenggang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China.
authors.forename: Rongguang
authors.initials: R
authors.lastname: Shao
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China.
authors.forename: Haigen
authors.initials: H
authors.lastname: Fu
authors.affiliation: College of Chemical Engineering, Qingdao University of Science and Technology , Qingdao 266042, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China.
authors.forename: Danqing
authors.initials: D
authors.lastname: Song
keywords: Sophoridine; antiproliferative; drug resistance; sophoridinol; structure−activity relationship