Unexpected regiospecific formation and DNA binding of new 3-(acridin-9-yl)methyl-2-iminothiazolidin-4-ones

Journal of Chemical Sciences

Mária Vilková¹  Júlia Kudláčová²  Danica Sabolová²  Ján Imrich1¹ 

[1] Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, P J Å afárik University, Moyzesova 11, 041 01 KoÅ¡ice, Slovakia$$;Department of Biochemistry, Institute of Chemistry, Faculty of Science, P J Å afárik University, Moyzesova 11, 041 01 KoÅ¡ice, Slovakia$$

关键词: CT DNA;    acridine;    thiazolidinone;    intercalation;    DNA binding constants;    Stern-Volmer constants.;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

New 3-(acridin-9-yl)methyl-2-substituted imino-1,3-thiazolidin-4-ones were regiospecifically synthesized from unstable (acridin-9-yl)methyl thioureas and methyl bromoacetate (MBA) or bromoacetyl bromide (BAB). Unexpected formation of only one thiazolidinone regioisomer with both the reagents was due to a new mechanism involving a transient spiro 9,10-dihydroacridine intermediate. These results are in contrast with the reactions of acridin-9-yl thioureas with MBA/BAB that afforded two different thiazolidinone regioisomers with these reagents. UV-vis titrations, CD spectra, and fluorescence quenching have shown that new products intercalated into calf thymus (CT) DNA, and displaced ethidium bromide (EB) from a CT DNA–EB complex. Intrinsic binding constants, 𝐾𝑏, and Stern-Volmer constants, 𝐾𝑆𝑉 , were found in the range 0.79✕105 – 2.85✕105 M−1 and 17950 – 3360M−1, respectively. The strongest binding affinity was found for an electrondonated 2-(4-methoxyphenylimino) thiazolidinone. Additional evidence for DNA intercalation was obtained from thermal denaturation studies. Gel electrophoresis has proven that thiazolidinone products nicked the supercoiled plasmid DNA in 5.0 𝜇M concentration.

【 授权许可】

Unknown