Antitumor Effect And Pharmacokinetics Of N-Hydroxy-4-phenylacetylamino-N-p-tolyl-benzamide

Histone deacetylase inhibitors(HDACi)are much considered potential anticancer agents due to regulation of gene expression and histone acetylation.N-Hydroxy-4-phenylacetylamino-N-p-tolyl-benzamide(HPAPB)as hydroxamic acid HDACi of anticancer potent was synthesized,of which the proliferation inhibition with vorinostat(SAHA)as the positive control in A549,HeLa,HepG2,and EC 109 cell lines suggested that HPAPB dramatically inhibited the proliferation of HepG2 and A549(100?M<IC50<200?M),and the pharmacological evaluation in mice did that cancer inhibition of HPAPB was equal to the one of SAHA,however the toxicity(LD50=1.29g/kg)of HPAPB was that less than the one(LD50=0.77g/kg)of SAHA.Based on the established HPLC determination with C18 column(4.6 mm×250mm,5um),283nm detection wavelength,mobile phase(methanol:water with 0.1 formic acid=68:32),1.0mL/min flow rate,and 30?column temperature of HPAPB content,the analysis method of biological samples of HPAPB was identified,and performance in pharmacokinetic determination of HPAPB in rat resulted in concentration-time curve and pharmacokinetic parameters,such as the concentration variation of HPAPB suitable for two-compartment model,t1/2=0.592h,V1?1.475,CL=0.611,AUC(0-?)=40.942,and C= 15.981e-1.171t+ 0.967e-0.018t.