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 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, K b , and Stern-Volmer constants, K SV , 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 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.

Derivatives Incorporating Acridine, Pyrrole, and Thiazolidine Rings as Promising Antitumor Agents

“…Despite the potential for obtaining two regioisomeric products, the treatment of the spiro compounds 6a-e with MBA, DEAD, EBP, and EBV yielded only a single product 7-10, as evidenced by the 1 H NMR spectra of the reaction mixtures. This outcome was consistent with previous findings in similar systems, where MBA, bromoacetyl bromide, or DEAD yielded exclusively one regioisomer, as observed with (acridin-9-yl)methylthioureas [27] and 3-[(E)-[(acridin-9-yl)methylidene]amino]-1substituted thioureas [28]. Our results demonstrate the simple regioselective formation of the novel spiro acridine thiazolidinones 7-10, the structures of which were confirmed by 1D and 2D experiments (Figure 5).…”

Anti-proliferative activity, molecular modeling studies and interaction with calf thymus DNA of novel ciprofloxacin analogues

“…The spectroscopic changes of EB-CtDNA are often utilized to study the interaction between CtDNA and newly synthesized molecule. [38][39][40] The quenching of EB-CtDNA by the synthesized compound 3o is in good agreement with the linear Stern-Volmer equation, which gives additional evidence that 3o binds to DNA.…”