Dialquilfosforilidrazonas e N,N-bis(diisobutilfosforiltioamida)diaminas: síntese, caracterização, modelagem molecular e estudo da atividade biológica

Abstract

A series of 22 dialkylphosphorylydrazones (Dialkyl esther, N -[(1E)-(R1 phenyl)methylene]phosphorohydrazidic acid), 20 of them new along with 3 new N,N -bis (diisobutylphosphorylthioamide)diamines (Bis-[Diisobutyl esther), N-thioxomethylene]-, diamine)phosphoramidic acid were prepared and characterized by IR, 1H-NMR, 13C-NMR, 31P-NMR and mass spectrometry. The analysis of 1H-NMR, 13C-NMR, 31P-NMR and NOE spectra confirmed the obtention of the single diastereoisomer E in the synthesis of dialkylphosphorylydrazones. The results of a molecular modeling study performed in order to investigate the mechanism of the synthesis of dialkylphosphorylydrazones are in agreement with the experimental results, i.e., the favoured formation of diastereoisomer E over Z. All compounds were evaluated for their capacity to inhibit diphenolase activity of the tyrosinase enzyme. Compounds 5, 8 and 13 show major inhibitory effects, with IC50 values of 102.58 μM, 191.44 μM and 210.81 μM, respectively. These dialkylphosphorylydrazones were also evaluated for their antinociceptive, pharmacological and toxicological effects in tests with mice. None of them showed any activity up to a concentration of 100 mg/kg. All compounds were tested against Musca domestica and showed no activity. The molecular modeling study confirmed the inefficiency of these compounds to act as insecticides, since their interaction with AChE is reversible and does not reach the aging (irreversible) step.