Bouz Ghada, Bouz Sarah, Janďourek Ondřej, Konečná Klára, Bárta Pavel, Vinšová Jarmila, Doležal Martin, Zitko Jan
Faculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech Republic.
Pharmaceuticals (Basel). 2021 Aug 4;14(8):768. doi: 10.3390/ph14080768.
Despite the established treatment regimens, tuberculosis remains an alarming threat to public health according to WHO. Novel agents are needed to overcome the increasing rate of resistance and perhaps achieve eradication. As part of our long-term research on pyrazine derived compounds, we prepared a series of their ortho fused derivatives, -phenyl- and -benzyl quinoxaline-2-carboxamides, and evaluated their in vitro antimycobacterial activity. In vitro activity against H37Ra (represented by minimum inhibitory concentration, MIC) ranged between 3.91-500 µg/mL, with most compounds having moderate to good activities (MIC < 15.625 µg/mL). The majority of the active compounds belonged to the -benzyl group. In addition to antimycobacterial activity assessment, final compounds were screened for their in vitro cytotoxicity. -(naphthalen-1-ylmethyl)quinoxaline-2-carboxamide (compound ) was identified as a potential antineoplastic agent with selective cytotoxicity against hepatic (HepG2), ovarian (SK-OV-3), and prostate (PC-3) cancer cells lines. Molecular docking showed that human DNA topoisomerase and vascular endothelial growth factor receptor could be potential targets for .
尽管已有既定的治疗方案，但据世界卫生组织称，结核病仍然是对公共卫生的一个惊人威胁。需要新型药物来克服不断上升的耐药率，并有可能实现根除。作为我们对吡嗪衍生化合物长期研究的一部分，我们制备了一系列它们的邻位稠合衍生物，即 - 苯基 - 和 - 苄基喹喔啉 -2- 甲酰胺，并评估了它们的体外抗分枝杆菌活性。对 H37Ra 的体外活性（以最低抑菌浓度，即 MIC 表示）在 3.91 - 500 µg/mL 之间，大多数化合物具有中度至良好的活性（MIC < 15.625 µg/mL）。大多数活性化合物属于 - 苄基基团。除了抗分枝杆菌活性评估外，还对最终化合物进行了体外细胞毒性筛选。 -（萘 -1- 基甲基）喹喔啉 -2- 甲酰胺（化合物 ）被鉴定为一种潜在的抗肿瘤药物，对肝癌（HepG2）、卵巢癌（SK-OV-3）和前列腺癌（PC-3）细胞系具有选择性细胞毒性。分子对接表明，人 DNA 拓扑异构酶和血管内皮生长因子受体可能是 的潜在靶点。
