Alafeefy Ahmed M, Ashour Abdelkader E, Prasad Onkar, Sinha Leena, Pathak Shilendra, Alasmari Fatimah A, Rishi Arun K, Abdel-Aziz Hatem A
Department of Pharmaceutical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, P.O. Box 173, Alkharj, 11942, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
Eur J Med Chem. 2015 Mar 6;92:191-201. doi: 10.1016/j.ejmech.2014.12.048. Epub 2014 Dec 27.
The reaction of N-(2-(hydrazinecarbonyl)aryl)benzamides 2a, b with indoline-2,3-diones 4ae in acidified ethanolic solution furnished the corresponding N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)benzamides 5aj, respectively. Furthermore, 3-(2-oxoindolin-3-ylideneamino)-2-substituted quinazolin-4(3H)-ones 6aj were prepared by the reaction of 3-amino-2-arylquinazolin-4(3H)-one 3a, b with 4ae. Six derivatives of the twenty newly synthesized compounds showed remarkable antitumor activity against most of the tested cell lines, Daoy, UW228-2, Huh-7, Hela and MDA-MB231. Although these six compounds were more potent than the standard drug (CFM-1), indeed compounds 5b, 5d and 6b were the best candidates with IC50 values in the range 1.866.87, 4.4210.89 and 1.468.60 μg/ml and percentage inhibition in the range 77.188.7, 59.4184.8 and 75.488.0%, respectively. QSAR analyses on the current series of derivatives also have been performed for all five cancer cell lines and thus 10 statistically significant models were developed and internally cross validated.
N-(2-(肼基羰基)芳基)苯甲酰胺2a、b与吲哚啉-2,3-二酮4a - e在酸化乙醇溶液中的反应分别得到了相应的N-(2-(2-(2-氧代吲哚啉-3-亚基)肼基羰基)苯基)苯甲酰胺5a - j。此外，3-氨基-2-芳基喹唑啉-4(3H)-酮3a、b与4a - e反应制备了3-(2-氧代吲哚啉-3-亚基氨基)-2-取代喹唑啉-4(3H)-酮6a - j。二十种新合成化合物中的六种衍生物对大多数测试细胞系，即道氏细胞系、UW228-2、Huh-7、Hela和MDA-MB231显示出显著的抗肿瘤活性。尽管这六种化合物比标准药物（CFM-1）更有效，但实际上化合物5b、5d和6b是最佳候选物，其IC50值分别在1.86 - 6.87、4.42 - 10.89和1.46 - 8.60μg/ml范围内，抑制率分别在77.1% - 88.7%、59.4% - 184.8%和75.4% - 88.0%范围内。还对当前系列衍生物针对所有五种癌细胞系进行了定量构效关系（QSAR）分析，从而开发了10个具有统计学意义的模型并进行了内部交叉验证。
