Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), P.O. Box: 90950, Riyadh 11623, Saudi Arabia.
Photochemistry Department, (Heterocyclic & Nucleosides Unit), National Research Centre, Cairo, Egypt.
Curr Org Synth. 2020;17(1):55-64. doi: 10.2174/1570179417666191223163225.
A novel series of pyridine containing 1,3,4-oxa/thiadiazol derivatives 4a,b, pyrazole derivatives 5-7, thiazole derivatives 9a,b and 17a-c, urea derivatives 12a-c, imidiazole derivative 16, imidazo[1,2-a]pyridine derivatives 18a, b, tetrazole 19, pyrane 20 and pyridine derivatives 21 has been synthesized.
This research aims to synthesize 6-(Trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl] amino} nicotinohydrazide 2 and 6-(trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl]amino} pyridin-3-carboaldhyde 15 as key intermediate for the synthesis of novel pyridine derivatives bearing different heterocyclic rings in order to study the additive effect of this ring toward tumor cell lines.
6-(Trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl]amino} nicotinohydrazide 2 was synthesized in a series of synthetic steps and was used as key intermediate for the synthesis of compounds 3-(1,3,4- oxa/thiadiazol-2-yl)-6-(trifluoromethyl)-N-(3- trifluoromethyl) phenyl) pyridin-2-amine 4a,b, (3,5-dimethyl- 1H-pyrazol-1-yl derivatives) [6-(trifluoromethyl)-2-{[3- trifluoromethyl) phenyl] amino} pyridin-3- yl]methanone 5a,b, 6-8, 9a,b and 12a-c. Also, 6-(trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl]amino} pyridin-3-carboaldhyde (15) was used as a key intermediate for the synthesis of novel series of pyridine derivatives with different heterocyclic ring (16-21).
Structures of the newly synthesized compounds were established by elemental analysis and spectral data. All the synthesized compounds were screened for their in vitro anticancer activity against liver cancer (HepG2), human colon cancer (HT-29) and human breast adenocarcinoma cell lines (MCF-7).
All the synthesized compounds were investigated for their in vitro antitumor activity. Compounds 4b, 9a,b and 19 showed higher antitumor activity than the doxorubicin. Interestingly, pyridine with pfluorophenyl urea 12a demonstrated the most potent antitumor activity. The activity of these compounds is strongly dependent on the basic skeleton of the molecules and the nature of the heterocyclic ring attached to the pyridine moiety.
合成了一系列新型吡啶类化合物，包括含有 1,3,4-噁二唑/噻二唑的嘧啶衍生物 4a,b、吡唑衍生物 5-7、噻唑衍生物 9a,b 和 17a-c、脲衍生物 12a-c、咪唑衍生物 16、咪唑并[1,2-a]吡啶衍生物 18a,b、四唑 19、吡喃 20 和吡啶衍生物 21。
本研究旨在合成 6-(三氟甲基)-2-[[3-(三氟甲基)苯基]氨基]烟酰肼 2 和 6-(三氟甲基)-2-[[3-(三氟甲基)苯基]氨基]吡啶-3-甲酰醛 15，作为合成含有不同杂环的新型吡啶衍生物的关键中间体，以研究该环对肿瘤细胞系的附加作用。
通过一系列合成步骤合成 6-(三氟甲基)-2-[[3-(三氟甲基)苯基]氨基]烟酰肼 2，并将其用作合成化合物 3-(1,3,4-噁二唑-2-基)-6-(三氟甲基)-N-(3-三氟甲基)苯基)吡啶-2-胺 4a,b、(3,5-二甲基-1H-吡唑-1-基衍生物)[6-(三氟甲基)-2-[[3-(三氟甲基)苯基]氨基]吡啶-3-基]甲酮 5a,b、6-8、9a,b 和 12a-c 的关键中间体。此外，6-(三氟甲基)-2-[[3-(三氟甲基)苯基]氨基]吡啶-3-甲酰醛 (15) 也被用作合成具有不同杂环的新型吡啶衍生物系列的关键中间体 (16-21)。
通过元素分析和光谱数据确定了新合成化合物的结构。所有合成的化合物均进行了体外抗癌活性筛选，包括肝癌 (HepG2)、人结肠癌细胞 (HT-29) 和人乳腺癌腺癌细胞系 (MCF-7)。
所有合成的化合物均进行了体外抗肿瘤活性研究。化合物 4b、9a,b 和 19 显示出比多柔比星更高的抗肿瘤活性。有趣的是，带有对氟苯基脲的吡啶 12a 表现出最强的抗肿瘤活性。这些化合物的活性强烈依赖于分子的基本骨架和连接到吡啶部分的杂环的性质。
