Synthesis, DNA Interaction, and Cytotoxic Activity of a Novel Proflavine-Dithiazolidinone Pharmacophore

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• 作者：Ladislav Janovec ; Danica Sabolov&aacute ; M&aacute ; ria Ko//pubs.acs.org/images/entities/zcaron.gif" border="0">urkov&aacute ; Helena Paulí ; kov&aacute ; Pavol Kristian ; J&aacute ; n
• 刊名：Bioconjugate Chemistry
• 出版年：2007
• 出版时间：January 2007
• 年：2007
• 卷：18
• 期：1
• 页码：93 - 100
• 全文大小：338K
• 年卷期：v.18,no.1(January 2007)
• ISSN：1520-4812

文摘

Five novel proflavine-dithiazolidinone derivatives 4a-4e have been designed and synthesized by the reaction ofdialkyl acridin-3,6-diyl dithioureas 3a-3e with methyl bromoacetate. The binding affinity of dithiazolidinonehydrochlorides 5a-5e with calf thymus DNA and plasmid (pUC19) DNA was investigated by a variety ofspectroscopic techniques including UV-vis, fluorescence, and CD spectroscopy. The effects of 5a-5e on thethermal denaturation profiles of calf thymus DNA were also studied. From spectrophotometric and spectrofluorimetric titrations, the binding constants for the pUC19 DNA-drug complexes were determined (K = 6.2-2.2 ×10⁴ M^-1). In vitro cytotoxic activities of compounds 5a-5e toward murine leukemia cell line L1210 and humanuterus carcinoma HeLa cells were also examined. 2',2' '-[(Acridin-3,6-diyl)diimino]-3',3' '-dipropyl-1,3-dithiazolidin-4-one hydrochloride (5b) showed the highest activity against these cells with IC₅₀ values of 6.3 M and 12.9 Mover the course of 72 h.