Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Department of Drug Radiation Research, National Center for Radiation Research and Technology, Nasr City, Cairo 113701, Egypt.
Int J Mol Sci. 2014 May 2;15(5):7539-53. doi: 10.3390/ijms15057539.
4-Aminoantipyrine was utilized as key intermediate for the synthesis of pyrazolone derivatives bearing biologically active moieties. The newly synthesized compounds were characterized by IR, 1H- and 13C-NMR spectral and microanalytical studies. The compounds were screened as anticancer agents against a human tumor breast cancer cell line MCF7, and the results showed that (Z)-4-((3-amino-5-imino-1-phenyl-1H-pyrazol-4(5H)-ylidene)methylamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 5, 3-(4-bromophenyl) -1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 13, 1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-(4-iodophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 14, 3,3'-(4,4'-sulfonylbis(4,1-phenylene))bis(1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) 16, (Z)-1- (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-hydrazono-4-oxo-3-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 17, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl- 2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-3-phenyl-2-(2-phenylhydrazono)-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile 18, and (Z)-4-(3-amino-6-hydrazono-7-phenyl-6,7-dihydro pyrazolo[3,4-d]pyrimidin-5-yl)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 19 were the most active compounds with IC50 values ranging from 30.68 to 60.72 µM compared with Doxorubicin as positive control with the IC50 value 71.8 µM.
4-氨基安替比林被用作合成含有生物活性部分的吡唑啉衍生物的关键中间体。新合成的化合物通过 IR、1H- 和 13C-NMR 光谱和微量分析研究进行了表征。这些化合物被筛选为针对人肿瘤乳腺癌 MCF7 细胞系的抗癌剂,结果表明,(Z)-4-((3-氨基-5-亚氨基-1-苯基-1H-吡唑-4(5H)-基)亚甲基氨基)-1,5-二甲基-2-苯基-1,2-二氢吡唑-3-酮 5、3-(4-溴苯基)-1-(1,5-二甲基-3-氧代-2-苯基-2,3-二氢-1H-吡唑-4-基)-4-氧代-2-硫代-1,2,3,4-四氢嘧啶-5-甲腈 13、1-(1,5-二甲基-3-氧代-2-苯基-2,3-二氢-1H-吡唑-4-基)-3-(4-碘苯基)-4-氧代-2-硫代-1,2,3,4-四氢嘧啶-5-甲腈 14、3,3' -(4,4'-磺酰基双(4,1-亚苯基))双(1-(1,5-二甲基-3-氧代-2-苯基-2,3-二氢-1H-吡唑-4-基)-4-氧代-2-硫代-1,2,3,4-四氢嘧啶-5-甲腈 16、(Z)-1-(1,5-二甲基-3-氧代-2-苯基-2,3-二氢-1H-吡唑-4-基)-2-肼基-4-氧代-3-苯基-1,2,3,4-四氢嘧啶-5-甲腈 17、(Z)-1-(1,5-二甲基-3-氧代-2-苯基-2,3-二氢-1H-吡唑-4-基)-4-氧代-3-苯基-2-(2-苯基肼基)-1,2,3,4-四氢嘧啶-5-甲腈 18 和(Z)-4-(3-氨基-6-肼基-7-苯基-6,7-二氢吡唑并[3,4-d]嘧啶-5-基)-1,5-二甲基-2-苯基-1,2-二氢吡唑-3-酮 19 是最具活性的化合物,其 IC50 值范围为 30.68 至 60.72 µM,与阳性对照多柔比星的 IC50 值 71.8 µM 相比。