摘要
以2,4-噻唑烷二酮和取代芳香醛为起始原料,反应得到一系列2,4-噻唑烷二酮衍生物,并对所合成化合物进行了抑制酪氨酸酶活性测试,结果表明化合物均有一定的抑制酪氨酸酶活性,化合物1((E)-5-(3-氯苯亚甲基)噻唑烷-2,4-二酮)和化合物2((E)-5-(2,4-二氯苯亚甲基)噻唑烷-2,4-二酮)活性强于阳性对照曲酸,其中化合物1表现出最好的抑制酪氨酸酶活性,其IC_(50)值为18. 43μmol/L。优选化合物1进行了抑制机理探讨,结果表明其为不可逆抑制剂,同时对化合物1进行了分子对接研究。
A series of 2,4-thiazolidinedione derivatives were synthesized from 2,4-thiazolidinedione and aromatic substituted aldehydes. The tyrosinase inhibitory activity of the synthesized compounds was tested. The results indicate that all the synthesized compounds have some tyrosinase inhibitory activity. Compound 1((E)-5-(3-chlorobenzomethylene) thiazolidine-2,4-dione) and compound 2((E)-5-( 2,4-dichlorobenzomethylene)thiazolidine-2,4-dione) activity are stronger than the other compounds,especially,compound 1 shows more potent inhibitory effect than the positive control kojic acid,its IC_(50) value is 18. 43μmol/L. The inhibitory mechanism of compound 1 was studied,and the result showed that it was an irreversible inhibitor. Molecular docking study of compound 1 was also carried out.
引文
[1]SONG K K,HUANG H,HAN P.Inhibitory effects of cis and trans-isomers of 3,5-dihydroxystibene on the activity of mushroom tyrosinase[J].Biochemical&Biophysical Research Communications,2006,342(4):1147-1151.
[2]ZHENG Z P,ZHANG Y N,ZHANG S.One-pot green synthesis of 1,3,5-triarylpentane-1,5-dione and triarylmethane derivatives as a new class of tyrosinase inhibitors[J].Bioorganic&Medicinal Chemistry Letters,2016,26(3):795-798.
[3]TAN X,SONG Y H,PARK C,et al.Highlypotent tyrosinase inhibitor,neorau-flavane from campylotropis hirtella and inhibitory mechanismwith molecular docking[J].Bioorganic&Medicinal Chemistry,2016,24(2):153-159.
[4]GUERRERO A,ROSELL G.Biorational approaches for insect control by enzymatic inhibition[J].Current Medicinal Chemsitry,2005,12(4):461-469.
[5]GORMAN M J,AN C J,KANOST M R.Characterization of tyrosine hydroxylase from manduca sexta[J].Insect Biochemistry&Molecular Biology,2007,37(12):1327-1377.
[6]MOLINA-HOLGADO F,SALVAGE S.Synthesis,physical-chemical characterisation and biological evaluation of novel 2-amido-3-hydroxyp-yridin-4(1H)-ones:Iron chelators with the potential for treating alzheimer’s disease[J].Bioorganic&Medicinal Chemistry,2011,19(3):1285-1297.
[7]RIYADH S,GOMHA S,MAHMMOUD E,et al.Syntesis and anticancer acticities of thiazoles,1,3-thiazines and thiazolidine using chitosan-grafted-poly as basic catalyst[J].Cheminform,2016,46(38):1227-1243.
[8]KAPLANCIKLI Z,LEVENT S,OSMANIYE D,et al.Synthesis and anticandidal activity evaluation of new benzimidazole-thiazole derivatives[J].Molecules,2011,22(12):658.
[9]RACHEL C,MONICA K.In vitro anti-oxidant and anti-inflamma activity of newly synthesized schiff bases derived from 2-aminothiazole derivatives[J].Indo American Journal of Pharmaceutical Research,2015,5(5):2078-2088.
[10]SAEEDA,MAHESEAR P,CHANNAR P,et al.Sythesis,molecular docking studies of coemarinylpyrazolinyl substituted thiazoles as non-competitive inhibitors of mushroom tyrosinase[J].Bioorganic Chemistry,2017,74:187-196.
[11]LIUJ B,YI W,WAN Y Q,et al.1-(1-Arylethylidene)-thiosemicarbazide derivatives:a newclass of tyrosinase inhibitors[J].Bioorganic&Medicinal Chemistry,2008,16(3):1096-1102.
[12]TANG J Y,LIU J B,WU F Y.Molecular docking studies and biological evaluation of 1,3,4-thiadiazole derivatives bearing schiff base moieties as tyrosinase inhibitors[J].Bioorganic Chemistry,2016,12:29-36.