Activity evaluation for isohydroxamic acid compounds on mutant EGFR cell lines
Objective To design and synthesize novel compounds that possessed the anti-proliferative activities against non-small cell lung cancer(NSCLC)cell lines with mutant epidermal growth factor receptor(EGFR).Methods A series of isohydroxamic acid derivatives were synthesized from the raw material of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine through seven steps.The anti-proliferative activities against cell lines with wild EGFR and mutant EGFR for target compounds were test by MTT assay.Results All compounds were identified by NMR and MS.In vitro bioactivities study demonstrated that compounds(A1-A2,A4-A6)with straight chain alkyl substituted isohydroxamic acid displayed anti-proliferative activities against EGFR mutant cell lines,whereas,the rest compounds including A3 and B1-B4 gave the negative results.Among them,compound A4 exhibited the best anti-proliferative activity against PC9,HCC827 and H1975 with ID50 values smaller than 7 μmol·L-1,which was similar to that of the positive control N′-Hydroxy-N-phenyloctanediamide(SAHA).Moreover,compound A4 could not inhibit the proliferation of EGFR wild type cell lines H460(ID50>32 μmol·L-1)and A549(ID50>32 μmol·L-1),suggesting the good selectivity of A4 had a good selectivity.Conclusions compound A4 can be regard as a lead compound for the developing of mutant EGFR inhibitors.
NETL
NSTL
万方数据
