Structure-Activity Relationships for the 9-(Pyridin-2’-yl)- aminoacridines 英文参考文献.docVIP

Molecules 2004, 9, 102-108 molecules ISSN 1420-3049 Structure-Activity Relationships for the 9-(Pyridin-2’-yl)- aminoacridines Michael D. Mosher *, Kristi L. Holmes and Katherine S. Frost Department of Chemistry, University of Nebraska at Kearney, 905 W. 25 St., Kearney, Nebraska th 68849-1150, USA. Tel. +1-(308)-865-8385, Fax +1-(308) 865-8399. * Author to whom correspondence should be addressed; e-mail: mosherm@ Received: 19 January 2004 / Accepted: 25 January 2004 / Published: 28 Febraury2004 Abstract: A series of 9-(pyridin-2’-yl)-aminoacridines was prepared and analyzed for their ability to change the thermal denaturation temperature of genomic calf thymus DNA. Development of a QSAR equation indicated that electron withdrawing groups on the pyridine ring promoted the interaction with double stranded DNA. Keywords: Acridine, QSAR, pyridine, DNA. Introduction This year approximately 1.3 million new cancer cases will be diagnosed in the United States. This estimate does not include diagnoses of in situ non-invasive cancer or the approximately 1 million cases of non-melanoma skin cancer. According to the American Cancer Society, more than half a million Americans will die of cancer in 2004 – more than 1500 people each day [1]. The Morbidity and Mortality Weekly Report produced by the Centers for Disease Control reports that death rates in the United States have generally declined for some cancers, although many cancer death rates have risen [2]. Chemotherapeutic treatment of cancerous tissues has made little headway in the fight to rid the world of cancer.  103 Molecules 2004, 9 One area of advance has been in the use of DNA intercalating drugs such as m-amsacrine (m- AMSA, 1), a successful antiproliferative agent used in the fight against childhood leukemia (Scheme 1) [3]. The aminoacridines as a class, however, suffer from rapid metabolic decomposition via hydrolysis or thioly