Synthesis of calix [4]arene thiazole derivatives and investigation of their interactions with dna, acetylcholinesterase enzyme inhibition and antioxidant activities

In the present thesis, the interactions of novel thiazole-containing calix[4]arene compounds(5,7,8) with calf thymus DNA (CT-DNA) and plasmid DNA were investigated, along with their acetylcholinesterase (AChE) inhibitory potentials and antioxidant activities. Initially, the synthesis of thiazole -derived calixarene compounds was carried out, and their structural characterization was performed using FTIR, ¹H NMR, and ¹³C NMR spectroscopic techniques, along with elemental analysis. The interactions of the synthesized compounds with CT-DNA were investigated using UV-Vis absorption spectroscopy and fluorescence spectroscopy techniques. The UV-Vis spectroscopy results of the three compounds revealed a hyperchromic effect, indicating an increase in absorbance values. Fluorescence spectroscopy analyses revealed that the emission intensities of the compounds were quenched in the presence of CT-DNA. For the quantitative evaluation of these interactions, Stern–Volmer quenching constants (Ksv) were calculated. Additionally, the interactions between compounds (5, 7, and 8) and CT-DNA in the presence of ethidium bromide were investigated by fluorescence spectroscopy at different temperatures (298, 303, and 313 K). The observed decrease in both the Stern–Volmer quenching constant (Ksv) and the binding constant (Kb) with increasing temperature indicates that the fluorescence quenching occurs via a static mechanism. Furthermore, the binding characteristics were evaluated based on the calculated thermodynamic parameters (ΔH, ΔS, and ΔG). The negative value of the Gibbs free energy change (ΔG) indicates that the interaction between the calixarene compounds and DNA occurs spontaneously and is thermodynamically favorable. The negative values of both enthalpy (ΔH) and entropy (ΔS) suggest that the binding is driven by van der Waals forces and hydrogen bonding interactions. In another study, the effects of the compounds on DNA were evaluated through agarose gel electrophoresis experiments conducted with pBR322 plasmid DNA. In another study conducted to evaluate the biological potentials of the synthesized compounds, their acetylcholinesterase (AChE) inhibition activities were investigated; the IC₅₀ values of the compounds were determined, and their inhibitory effects were quantitatively evaluated. Based on enzyme kinetic analyses performed using the Lineweaver–Burk double reciprocal plot method, the inhibition mechanisms of the compounds on acetylcholinesterase (AChE) were evaluated, and the types of inhibition were accordingly characterized. The analyses revealed that Compound 5 exhibits uncompetitive inhibition on acetylcholinesterase, whereas Compounds 7 and 8 act as competitive inhibitors. In addition, the antioxidant activities of the calixarene compounds (5,7,8) were evaluated using the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging method, and the results of Compopunds indicated an antioxidant activity order of 7> 5 > 8. However, the antioxidant activities of all compounds were found to be lower compared to that of ascorbic acid, a widely used standard antioxidant. Keywords: Acetylcholinesterase, antioxidant, calixarene, CT-DNA, inhibition, thiazole