Rostom Sherif A F, Shalaby Manal A, El-Demellawy Maha A
Department of Medicinal Chemistry, Faculty of Medicine and Allied Sciences, King Abdul-Aziz University, PO Box 80205, Jeddah 21589, Saudi Arabia.
Eur J Med Chem. 2003 Nov-Dec;38(11-12):959-74. doi: 10.1016/j.ejmech.2003.08.003.
A novel series of 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazole-3-carboxylic acid hydrazide analogs and some derived 4-substituted-1,2,4-triazolin-3-thiones, 2-substituted-1,3,4-thiadiazole and 2-substituted-1,3,4-oxadiazoles has been synthesized. Ten of the newly synthesized compounds were selected by the National Cancer Institute (NCI)-in vitro-disease oriented antitumor screening to be evaluated for their antitumor activity. Seven compounds, namely 7a-c, 9, 11, 13 and 14, exhibited potential and broad spectrum antitumor activity against most of the tested subpanel tumour cell lines (GI50<100 microM). Compounds 14 (GI50, TGI, and LC50 MG-MID values of 0.08, 15.8 and 64.6 microM, respectively) and 11 (GI50, TGI, and LC50 MG-MID values of 0.20, 11.7 and 87.1 microM, respectively) proved to be the most active members in this study with potential activity against all the tested subpanel tumour cell lines and particular effectiveness on the leukaemia subpanel at both the GI50 (0.03 and 0.09 microM, respectively) and the TGI levels (35.2 and 28.1 microM, respectively). Moreover, compound 14 exhibited a super sensitivity profile towards about 26 different cancer cell lines with GI50 values lying in the nanomolar concentration range (GI50 values<0.01 microM). In addition, compounds 2-5, 6a-d, 7a, 8-11, 12a, 13, 14 were investigated for their in vitro effect on the replication of hepatitis-C virus (HCV) in HepG2 hepatocellular carcinoma cell line infected with the virus using the reverse transcription-polymerase chain reaction (RT-PCR) technique. The results revealed that compounds 2 and 5 were capable of inhibiting the replication of both the HCV RNA (+) and (-) strands at 10-100 microg mL(-1) concentration range.
合成了一系列新型的1-(4-氯苯基)-4-羟基-1H-吡唑-3-羧酸酰肼类似物以及一些衍生的4-取代-1,2,4-三唑啉-3-硫酮、2-取代-1,3,4-噻二唑和2-取代-1,3,4-恶二唑。美国国立癌症研究所（NCI）进行了以疾病为导向的体外抗肿瘤筛选，从新合成的化合物中挑选了10种来评估其抗肿瘤活性。7种化合物，即7a - c、9、11、13和14，对大多数测试的亚组肿瘤细胞系表现出潜在的广谱抗肿瘤活性（GI50 < 100 microM）。化合物14（GI50、TGI和LC50的MG - MID值分别为0.08、15.8和64.6 microM）和11（GI50、TGI和LC50的MG - MID值分别为0.20、11.7和87.1 microM）被证明是本研究中最具活性的成员，对所有测试的亚组肿瘤细胞系都有潜在活性，并且在GI50（分别为0.03和0.09 microM）和TGI水平（分别为35.2和28.1 microM）时对白血病亚组具有特别的有效性。此外，化合物14对约26种不同的癌细胞系表现出超敏反应，其GI50值处于纳摩尔浓度范围（GI50值< 0.01 microM）。另外，使用逆转录 - 聚合酶链反应（RT - PCR）技术研究了化合物2 - 5、6a - d、7a、8 - 11、12a、13、14对感染该病毒的HepG2肝癌细胞系中丙型肝炎病毒（HCV）复制的体外影响。结果显示，化合物2和5在10 - 100 microg mL(-1)浓度范围内能够抑制HCV RNA（+）和（-）链的复制。
