title: Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents.
abstract: Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3'-substituents at the 11-side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a-b, alkenes 7a-b and sophoridinic amines 14a-b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class 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; Tianjin Medical University General Hospital, Tianjin 300052, 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: Cheng
authors.initials: C
authors.lastname: Ye
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: Wuli
authors.initials: W
authors.lastname: Zhao
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: Danqing
authors.initials: D
authors.lastname: Song
keywords: Anticancer; Drug resistance; Sophoridinic derivatives; Structure–activity  relationship; Synthesis