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

Abstract

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 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, K b , and Stern-Volmer constants, K S V , were found in the range 0.79 ×10 5 – 2.85 ×10 5 M −1 and 17950 – 3360 M −1, respectively. The strongest binding affinity was found for an electron-donated 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. New DNA-binders 3-(acridin-9-yl)methyl-2-R-imino-1,3-thiazolid-in-4-ones were regiospecifically synthesized from unstable (acridin-9-yl)methyl thioureas and methyl bromoacetate (MBA) or bromoacetyl bromide (BAB) by a mechanism involving a transient spiro 9,10-dihydroacridine intermediate.