Synthesis, Structure and Cytotoxic Activity of New Acetylenic Derivatives of Betulin

Molecules

Stanisᐪw Boryczka²  Ewa B𑦾nek²  Joanna Wietrzyk³  Katarzyna Kempińska³  Maria Jastrzᆛska¹  Joachim Kusz⁴ 

[1] Department of Solid State Physics, Institute of Physics, University of Silesia, 4 Uniwersytecka Str., 40-007 Katowice, Poland;Department of Organic Chemistry, Medical University of Silesia, 4 Jagiellonska Str., 41-200 Sosnowiec, Poland;Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla Str., 53-114 Wrocław, Poland;Department of Physics of Crystals, Institute of Physics, University of Silesia, 4 Uniwersytecka Str., 40-007 Katowice, Poland

关键词: acetylenic betulins;    synthesis;    crystal structure;    cytotoxic activity;   

DOI  :  10.3390/molecules18044526

来源: mdpi

【 摘 要 】

A new series of betulin derivatives containing one or two pharmacophores bearing an acetylenic and carbonyl function at the C-3 and/or C-28 positions has been synthesized and characterized by ¹H- and ¹³C-NMR, IR, MS and elemental analyses. The crystal structure of 28-O-propynoylbetulin was determined by X-ray structural analysis. All new compounds, as well as betulin, were tested in vitro for their antiproliferative activity against human SW707 colorectal, CCRF/CEM leukemia, T47D breast cancer, and against murine P388 leukemia and Balb3T3 normal fibroblasts cell lines. Most of the compounds showed better cytotoxicity than betulin and cisplatin used as reference agent. 28-O-Propynoylbetulin was the most potent derivative, being over 500 times more potent than betulin and about 100 times more cytotoxic than cisplatin against the human leukemia (CCRF/CEM) cell line, with an ID₅₀ value of 0.02 μg/mL.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.