Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Tatarstan 420088, Russia.
Laboratory of Plant Infectious Diseases, FRC Kazan Scientific Center of Russian Academy of Sciences, Kazan, Tatarstan 420111, Russia.
Int J Mol Sci. 2020 Nov 5;21(21):8292. doi: 10.3390/ijms21218292.
A series of novel 4-aminobenzofuroxan derivatives containing aromatic/aliphatic amines fragments was achieved via aromatic nucleophilic substitution reaction of 4,6-dichloro-5-nitrobenzofuroxan. The quantum chemistry calculations were performed to identify the factors affecting the regioselectivity of the reaction. The formation of 4-substituted isomer is favored both by its greater stability and the lower activation barrier. Antimicrobial activity of the obtained compounds has been evaluated and some of them were found to suppress effectively bacterial biofilm growth. Fungistatic activity of 4-aminobenzofuroxans were tested on two genetically distinct isolates of . The effect of some benzofuroxan derivatives is likely to be more universal against different varieties of compared with benzimidazole and carbendazim. Additionally, their anti-cancer activity in vitro has been tested. 4-aminofuroxans possessing aniline moiety showed a high selectivity towards MCF-7 and M-HeLa tumor cell lines. Moreover, they exhibit a significantly lower toxicity towards normal liver cells compared to Doxorubicin and Tamoxifen. Thus, benzofuroxans containing aromatic amines fragments in their structure are promising candidates for further development both as anti-cancer and anti-microbial agents.
一系列新型 4-氨基苯并呋咱衍生物含有芳香/脂肪胺片段，通过 4,6-二氯-5-硝基苯并呋咱的芳香亲核取代反应得到。进行了量子化学计算以确定影响反应区域选择性的因素。4-取代异构体的形成是有利的，因为它具有更高的稳定性和更低的活化能垒。对获得的化合物进行了抗菌活性评价，发现其中一些化合物能有效抑制细菌生物膜的生长。对两种遗传上不同的 进行了 4-氨基苯并呋咱的抑菌活性测试。与苯并咪唑和多菌灵相比，一些苯并呋咱衍生物对不同品种的 可能具有更普遍的作用。此外，还测试了它们的体外抗癌活性。含有苯胺部分的 4-氨基呋咱对 MCF-7 和 M-HeLa 肿瘤细胞系表现出高选择性。此外，与多柔比星和他莫昔芬相比，它们对正常肝细胞的毒性明显降低。因此，结构中含有芳香胺片段的苯并呋咱衍生物有望进一步开发为抗癌和抗菌药物。
