Analysis of ADMET biological activity indicators of 1-(2-thienoyl)-3,3,3-trifluoroacetone acylhydrazones
Abstract
The aim of this research was to conduct a comprehensive in silico evaluation of the ADMET biological activity properties of acylhydrazone derivatives (H<sub>2</sub>L<sup>1</sup>-H<sub>2</sub>L<sup>6</sup>) synthesized based on 1-(2-thienoyl)-3,3,3-trifluoroacetone. The synthesis was carried out at room temperature in ethanol, and the product yields were 60-70%. ADMET parameters were analyzed using the ADMETLAB online server. Analysis of physicochemical properties showed that the molecular weight ranged from 340.05 to 417.96 g/mol, and TPSA ranged from 58.53 to 101.67 Ų. QED values were in the range of 0.355-0.513, indicating that H2L1 has high drug-likeness. QED values ranged from 0.355 to 0.513, indicating that H<sub>2</sub>L<sup>1</sup> has high drug-likeness properties. In terms of absorption parameters, H2L6 showed the highest PAMPA permeability (0.971), while H2L3 had the highest F50% bioavailability (0.768). Distribution analysis revealed that all compounds had high plasma protein binding (97.93–98.953%) and minimal BBB penetration (0.0–0.003). Metabolism characteristics showed that all compounds strongly inhibited CYP1A2, CYP2C19, and CYP2C8 enzymes. Excretion parameters indicated that H<sub>2</sub>L<sup>3</sup> had the highest CLplasma (3.814) and the shortest T₁/₂ (0.942 hours), while H<sub>2</sub>L<sup>5</sup> had the lowest CLplasma (1.573) and the longest T₁/₂ (1.373 hours). Analysis of all parameters demonstrated that H<sub>2</sub>L<sup>3</sup> and H<sub>2</sub>L<sup>6</sup> compounds are promising candidates for pharmaceutical development.