Akbarzadeh Tahmineh, Noushini Saeedeh, Taban Somayeh, Mahdavi Mohammad, Khoshneviszadeh Mahsima, Saeedi Mina, Emami Saeed, Eghtedari Mohammad, Sarrafi Yaghoub, Khoshneviszadeh Mehdi, Safavi Maliheh, Divsalar Kouros, Moshafi Mohammad Hassan, Asadipour Ali, Sabourian Reyhaneh, Edraki Najmeh, Firouzi Omidreza, Miri Ramin, Shafiee Abbas, Foroumadi Alireza
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Mol Divers. 2015 May;19(2):273-81. doi: 10.1007/s11030-015-9566-6. Epub 2015 Jan 23.
A novel series of 3,4-diphenyl-7-(hetero)arylimidazo[2,1-c][1,2,4]triazin-6-amine derivatives were synthesized via three-component reaction of 5,6-diphenyl-1,2,4-triazin-3-amine, various aromatic aldehydes, and cyclohexyl isocyanide. All synthesized compounds were tested against HL60 (human promyelocytic leukemia), MOLT-4 (human T lymphoblastic leukemia), and MCF-7 (human breast adenocarcinoma) cell lines, as cytotoxic agents. The structure-activity relationships study revealed that the introduction of hydroxyl and methoxy groups on the 7-phenyl ring can modulate the cytotoxic activity of these compounds. Among the 7-aryl derivatives, 3-hydroxyphenyl and 3-hydroxy-4-methoxyphenyl derivatives (6h and 6o) were the most potent compounds against HL60 and MCF-7 cells (IC(50s) = 9.8 - 20.4 μM). However, the replacement of the 7-aryl moiety with pyridyl or furan-2-yl resulted in compounds 6p or 6r with more promising cytotoxicity against MOLT-4 cell line (IC50 values 12.1 and 13.0 μM, respectively). Also, the acridine orange/ethidium bromide staining assay in MCF-7 cells suggested that the cytotoxic activity of compound 6r occurs via apoptosis.
通过5,6-二苯基-1,2,4-三嗪-3-胺、各种芳香醛和环己基异氰化物的三组分反应，合成了一系列新型的3,4-二苯基-7-(杂)芳基咪唑并[2,1-c][1,2,4]三嗪-6-胺衍生物。所有合成的化合物都作为细胞毒性剂，针对HL60（人早幼粒细胞白血病）、MOLT-4（人T淋巴细胞白血病）和MCF-7（人乳腺腺癌）细胞系进行了测试。构效关系研究表明，在7-苯环上引入羟基和甲氧基可以调节这些化合物的细胞毒性活性。在7-芳基衍生物中，3-羟基苯基和3-羟基-4-甲氧基苯基衍生物（6h和6o）是对HL60和MCF-7细胞最有效的化合物（IC(50s)=9.8 - 20.4 μM）。然而，用吡啶基或呋喃-2-基取代7-芳基部分，得到了对MOLT-4细胞系具有更有前景的细胞毒性的化合物6p或6r（IC50值分别为12.1和13.0 μM）。此外，MCF-7细胞中的吖啶橙/溴化乙锭染色试验表明，化合物6r的细胞毒性活性是通过凋亡发生的。
