Abdel-Megeed Rehab M, Kadry Mai O, Fayed Dalia B, Abdel-Hamid Abdel-Hamid Z
Department of Therapeutic Chemistry, National Research Centre, El Buhouth St, Dokki, Cairo, 12622, Egypt.
Toxicol Rep. 2019 Mar 23;6:262-266. doi: 10.1016/j.toxrep.2019.03.003. eCollection 2019.
The expedient fungi (s) is able to thrive in many host niches including blood stream, skin, mucosal surfaces, and different body organs. Herein, the assessment of novel synthesized pyrimidine derivatives as anti fungal agent was investigated. Female albino mice were injected intraperitoneally by s (1.5 × 10 CFU). infected Mice then subjected to treatment with two different doses which was low (50 mg/kg) and high one (200 mg/kg) of diflucan in addition to the newly synthestic compounds (2-(4- (Pyridine- 2- yl) aminosulfonyle phenylamino) - 6 -(naphthalene-2- yl)-4-(pyridine-2- yl) n - 3 carbonitril) and (2-(4-(Pyrimidine-2- yl) aminosulfonyle phenylamino)- 6 -(naphthalene-2- yl)- 4 -(pyridine-2- yl) pyridine-3- carbonitril) donated as (C1 & C2, respectively). Three weeks later gene expression of renal alpha smooth muscle actin (α-SMA) and of cyclooxygenase-2 (COX-2) protein expression were assessed as well as serum malondialdehyde (MDA) and total antioxidant capacity in both kidney and brain tissues. Furthermore, acetylcholinestrase activity was assessed. significantly elevated serum MDA. On the other hand, injection revealed a significantly reduction in total antioxidant capacity in kidney as well as in brain tissue. Furthermore, acetylcholine assessment declared a significant elevation. All biochemical parametersۥ upset were modulated upon new synthesized compounds treatment. Molecular analyses declared a significant down - regulation in renal α -smooth muscle actin gene expression in addition to, a significant down- regulation in COX-2 protein expression. From data recorded, it could be concluded that, C2 in a dose 200 mg ∕kg noticeably declared a significant effect comparing with the other treated groups revealing its promising effect as anti-fungal agent.
该适宜真菌能够在许多宿主生态位中生长，包括血流、皮肤、黏膜表面和不同的身体器官。在此，对新型合成嘧啶衍生物作为抗真菌剂进行了评估。雌性白化小鼠腹腔注射该真菌（1.5×10菌落形成单位）。感染的小鼠随后接受两种不同剂量的治疗，即低剂量（50毫克/千克）和高剂量（200毫克/千克）的氟康唑，此外还使用新合成的化合物（2-(4-(吡啶-2-基)氨磺酰基苯氨基)-6-(萘-2-基)-4-(吡啶-2-基)吡啶-3-腈）和（2-(4-(嘧啶-2-基)氨磺酰基苯氨基)-6-(萘-2-基)-4-(吡啶-2-基)吡啶-3-腈），分别命名为（C1和C2）。三周后，评估肾脏α平滑肌肌动蛋白（α-SMA）的基因表达以及环氧合酶-2（COX-2）的蛋白表达，同时评估肾脏和脑组织中的血清丙二醛（MDA）和总抗氧化能力。此外，还评估了乙酰胆碱酯酶活性。血清MDA显著升高。另一方面，注射显示肾脏以及脑组织中的总抗氧化能力显著降低。此外，乙酰胆碱评估显示显著升高。所有失调的生化参数在新合成化合物治疗后均得到调节。分子分析表明，肾脏α平滑肌肌动蛋白基因表达显著下调，此外，COX-2蛋白表达也显著下调。从记录的数据可以得出结论，与其他治疗组相比，200毫克/千克剂量的C2明显显示出显著效果，表明其作为抗真菌剂具有良好的前景。
