Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents.
10.1016/j.apsb.2016.03.004
- Author:
Chongwen BI
1
,
2
;
Cheng YE
3
;
Yinghong LI
3
;
Wuli ZHAO
3
;
Rongguang SHAO
3
;
Danqing SONG
3
Author Information
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China
2. Tianjin Medical University General Hospital, Tianjin 300052, China.
3. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
Anticancer;
Drug resistance;
Sophoridinic derivatives;
Structure–activity relationship;
Synthesis
- From:
Acta Pharmaceutica Sinica B
2016;6(3):222-228
- CountryChina
- Language:English
-
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.
