Thermodynamics of Solution, Interaction with Calf Thymus DNA and Anticancer Activity of Phenylhydrazone Derivatives

摘要

The solubilities in water (W) and in 3 mol⋅L−1 aqueous acetonitrile at 298.15 K of thiophene-2-, furan-2- and pyrrole-2-carboxaldehyde phenylhydrazone along with their nitro and 2,4-dinitro derivatives, referred to as PCT, PCF, PCP, NPCT, NPCF, NPCP, DPCT, DPCF and DPCP, respectively, are reported. The standard Gibbs energy of transfer from W to solvent mixtures (DGtransf_W-mixDelta G^{mathrm{transf}}_{mathrm{W-mix}}) was estimated for each solute. The results indicate that the transfer process for all systems is a spontaneous process. Calculations under the scaled-particle theory suggest that the work of cavity creation (ΔΔG _c), which is associated with the transfer of the phenylhydrazone from W to mix, dominates the magnitude of D Gtransf_W-mixmathrm {Delta} G^{mathrm{transf}}_{mathrm{W-mix}}. UV spectroscopic measurements suggest that these compounds bind calf thymus(CT)-DNA via intercalation mode in a buffer–3 mol⋅L−1 acetonitrile solution. The binding constant (K _b) depends on the nitro-substitution on the phenyl moiety and the electronegativity of the heteroatom in the heterocyclic ring. The corresponding Gibbs energy of binding (DG_DNA-B0Delta G_{mathrm{DNA-B}}^{0}) of phenylhydrazone derivatives to CT-DNA shows a marked dependence with ΔΔG _c. The anticancer activity on human breast cancer cell lines MDA-231, MDA-435 and HT-29 human colon adenocarcinoma cell line was evaluated for the compounds NPCT, NPCF, DPCT and PCT.