کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2474491 1113143 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents
چکیده انگلیسی

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.

Taking compound 2 as the lead, structure–activity relationship (SAR) investigation was continuously developed on the variations of 3'-CH2OH at the 11–side chain from sophoridine, a Chinese natural antitumor medicine. Among them, compound 5a displayed a potent antiproliferative activity with an advantage of inhibiting drug-resistant cancer cells.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Acta Pharmaceutica Sinica B - Volume 6, Issue 3, May 2016, Pages 222–228
نویسندگان
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