Cytotoxicity of 1-Aryl-3-buthylamino-1-propanone Hydrochlorides against Jurkat and L6 Cells

被引:0
作者
Gul, Mustafa [2 ,3 ]
Mete, Ebru [4 ]
Atalay, Mustafa [3 ]
Arik, Mustafa [4 ]
Gul, Halise Inci [1 ]
机构
[1] Ataturk Univ, Fac Pharm, Dept Pharmaceut Chem, TR-25240 Erzurum, Turkey
[2] Ataturk Univ, Fac Med, Dept Physiol, TR-25240 Erzurum, Turkey
[3] Univ Kuopio, Fac Med, Inst Biomed, FIN-70211 Kuopio, Finland
[4] Ataturk Univ, Fac Sci, Dept Chem, TR-25240 Erzurum, Turkey
来源
ARZNEIMITTELFORSCHUNG-DRUG RESEARCH | 2009年 / 59卷 / 07期
关键词
Buthylamine acetophenones; synthesis; Cytotoxic agents; Jurkat cells; L6; cells; Mannich bases; BIS MANNICH-BASES; CORRESPONDING AZINE DERIVATIVES; CONJUGATED STYRYL KETONES; CELLULAR GLUTATHIONE; ANTIFUNGAL ACTIVITY; ANTICONVULSANT ACTIVITIES; ANTIINFLAMMATORY ACTIVITY; ANTIMICROBIAL EVALUATION; T-CELLS; MONO;
D O I
暂无
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
1-Aryl-3-buthylamino-1-propanone hydrochloride type mono Mannich bases were synthesized and their cytotoxicity was tested against transformed human T-lymphocytes (Jurkat cells) and rat skeletal muscle derived myoblasts (L6 cells). Aryl part was changed as phenyl in 1, 4-methylphenyl in 2, 4-chlorophenyl in 3, 4-fluorophenyl in 4, 4-bromophenyl in 5, 4-hydroxyphenyl in 6, 2-acethylthiophene in 7. Of the compounds synthesized, 2, 5, 6, and 7 are reported for the first time. Compounds 1-7 had 3.16, 3.13, 3.35, 2.87, 4.17, 2.60, and 3.04 times higher cytotoxic potency than the reference compound 5-fluorouracil (CAS 51-21-8) against Jurkat cells, respectively. Compounds 1, 3, 4, 5, 6, and 7 had 1.22, 1.46, 1.59, 2.18, 1.24, and 1.45 times higher cytotoxic potency than the reference compound 5-fluorouracil against L6 cells, respectively. Among the compounds tested, only compound 5 had almost equal cytotoxic potency with the reference compound melphalan (CAS 148-823) against Jurkat and L6 cells. All compounds synthesized showed higher cytotoxic activity against Jurkat cells compared with L6 cells. Specifically, compounds 1-7 had 2.05, 2.68, 1.82, 1.43, 1.51, 1.66, and 1.66 times higher cytotoxicity against Jurkat cells compared with L6 cells. In Jurkat cells, there was a significant negative correlation between Log P and IC50 values (correlation coefficient: -0.955, p = 0.03), which actually means a positive correlation between the Log P and the cytotoxic activity of the compounds. These results suggest that the most potent compound 5 (a 4-bromo derivative) against both cell lines may serve as a model compound to develop new cytotoxic agents for further studies.
引用
收藏
页码:364 / 369
页数:6
相关论文
共 43 条
[1]   ANTICONVULSANT ACTIVITY OF INDANYLSPIROSUCCINIMIDE MANNICH-BASES [J].
BORENSTEIN, MR ;
DOUKAS, PH .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1987, 76 (04) :300-302
[2]  
Canturk P, 2008, ARZNEIMITTELFORSCH, V58, P686
[3]  
CHEN H T, 1991, Yaoxue Xuebao, V26, P183
[4]  
Dimmock JR, 1997, CURR MED CHEM, V4, P1
[5]  
Dimmock JR, 1998, PHARMAZIE, V53, P702
[6]  
DIMMOCK JR, 1994, PHARMAZIE, V49, P909
[7]   ANTICONVULSANT PROPERTIES OF SOME MANNICH-BASES OF CONJUGATED ARYLIDENE KETONES [J].
DIMMOCK, JR ;
JONNALAGADDA, SS ;
PHILLIPS, OA ;
ERCIYAS, E ;
SHYAM, K ;
SEMPLE, HA .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1992, 81 (05) :436-440
[8]   ANTIMICROBIAL EVALUATION OF SOME STYRYL KETONE DERIVATIVES AND RELATED THIOL ADDUCTS [J].
ERCIYAS, E ;
ERKALELI, HI ;
COSAR, G .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1994, 83 (04) :545-548
[9]  
Freshny R.I., 2005, CULTURE ANIMAL CELLS
[10]  
Gul H I, 2000, Pharm Acta Helv, V74, P393, DOI 10.1016/S0031-6865(00)00022-4