Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Division, National Research Center, El Buhouth Street, Dokki, Cairo 12622, Egypt.
Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Biomed Res Int. 2020 Dec 23;2020:8649745. doi: 10.1155/2020/8649745. eCollection 2020.
In the present work, a new series of dihydronaphthalene derivatives were synthesized starting with 6-methoxy-1-tetralone , and the corresponding hydrazine derivative . Reaction of compound with aryl isothiocyanates produced thiosemicarbazides , which were reacted with ethyl chloroacetate to give thiazolidinone derivatives . Pyrano thiazolecarbonitrile derivatives - were prepared by heating a mixture of compounds or , aryl aldehydes, and malononitrile utilizing distilled water in the presence of catalytic amount of potassium hydrogen phthalate. Also, treatment of with DMF-DMA under solvent-free conditions gave enaminone derivative , which condensed with ethyl acetoacetate or acetylacetone or malononitrile or cyanothioacetamide to give compounds -, respectively. Finally, reaction of the enaminone with 2-aminoimidazol or 2-aminothiazol in the presence of glacial acetic acid produced derivatives and , respectively. Cytotoxic evaluation of eleven compounds, against MCF-7 (human breast adenocarcinoma) cell lines, was estimated. Results revealed that five of the examined compounds , , , , and showed potent cytotoxic activities recording, IC values; 0.93 ± 0.02, 1.76 ± 0.04, 2.36 ± 0.06, 2.83 ± 0.07, and 3.73 ± 0.09 M, respectively, which were more potent than the reference used (Saturosporin, IC6.08 ± 0.15 M). The new products were also examined towards normal epithelial breast cells (MCF10A). All of them showed very good safety profile with different degrees and were safer than the reference drug used. Compound was the most effective against MCF-7 cells and was less toxic than Saturosporin by about 18.45-folds towards MCF01A normal cells. All the new compounds were fully characterized by the different spectral and analytical tools. Herein, detailed syntheses, spectroscopic, and biological data are reported.
在本工作中，以 6-甲氧基-1-四氢萘酮 为起始原料合成了一系列新的萘二氢衍生物，以及相应的肼衍生物。化合物 与芳基异硫氰酸酯反应生成缩氨基硫脲，然后与氯乙酸乙酯反应得到噻唑啉酮衍生物。通过在催化量的邻苯二甲酸氢钾存在下，将化合物 或 、芳基醛和丙二腈在蒸馏水中加热，制备了吡喃并噻唑甲腈衍生物 。此外，在无溶剂条件下，用 DMF-DMA 处理 得到烯胺酮衍生物 ，该衍生物与乙酰乙酸乙酯、乙酰丙酮、丙二腈或氰基硫代乙酰胺缩合，分别得到化合物 。最后，烯胺酮 与 2-氨基咪唑或 2-氨基噻唑在冰醋酸存在下反应，分别得到衍生物 。对 11 种化合物进行了对 MCF-7（人乳腺癌腺癌细胞系）的细胞毒性评估。结果表明，在所检查的五种化合物 、 、 、 、中，五种化合物 、 、 、 、表现出较强的细胞毒性活性，IC 值分别为 0.93 ± 0.02、1.76 ± 0.04、2.36 ± 0.06、2.83 ± 0.07 和 3.73 ± 0.09 M，比参考药物 Saturosporin（IC6.08 ± 0.15 M）更有效。新产物也对正常上皮乳腺细胞（MCF10A）进行了测试。所有化合物均表现出不同程度的良好安全性，且比所用参考药物更安全。化合物 对 MCF-7 细胞的抑制作用最强，对 MCF01A 正常细胞的毒性比 Saturosporin 低约 18.45 倍。所有新化合物均通过不同的光谱和分析工具进行了充分的表征。本文详细报道了它们的合成、光谱和生物学数据。
