Sulfaphenazole is a sulfonamide antibacterial drug. It competitively inhibits bacterial dihydrofolate synthase, blocking bacterial folate synthesis and thereby inhibiting bacterial growth and reproduction [1]. Sulfaphenazole is a selective inhibitor of the human cytochrome P450 (CYP) 2C9 enzyme [2]. Sulfaphenazole is a cytoprotective agent that prevents light-induced photoreceptor cell death. Sulfaphenazole inhibits light-induced necrosis and apoptosis triggered by mitochondrial stress [3].
In yeast expressed human cytochromes P450 of the 1A, 3A, and 2C subfamilies, Sulfadilamide acts as a strong and competitive inhibitor of CYP 2C9 with the Ki value of 0.3±0.1μM. The Ki values of Sulfadilamide for CYP 2C8 and 2C18 were 63 and 29μM, respectively. Sulfaphenazole failed to inhibit CYP 1A1, 1A2, 3A4, and 2C19 [2]. Sulfaphenazole (10μM; 1h) causes the numbers of light-induced apoptotic and necrotic cells decreased by 33 and 44%, respectively[3].
In a model of Diabetic male mice (db/db strain), Sulfaphenazole(5.13mg/kg; po; 8 weeks) reduces oxidative stress (measured as plasma levels of 8-isoprostane), increases NO bioavailability (measured as NO2−), and restores endothelial function in db/db mice without affecting plasma glucose levels [4]. Sulfaphenazole (100µL; ip; 15d) exposure post-injury was found to improve tissue perfusion in mouse models of both thermal injury and I/R-induced pressure injury, leading to reduced overall severity, improved wound closure and increased scar tensile strength [5]. In a rat model of myocardial ischemia-reperfusion (I/R) injury, Sulfaphenazole (30mg/kg; iv) treatment restored cardiac function and reduced myocardial infarct size. Furthermore, Sulfaphenazole reduced superoxide anion levels and enhanced NO bioavailability in reperfused hearts [6]. In a rat model of acute myocardial infarction (MI), Sulfaphenazole (8.1mg/kg; ip; 3d) pretreatment of rats with ameliorated I=R-induced myocardial damage and improved cardiac contractile functions by decreasing superoxide production, peroxynitrite formation, and by enhancing NO bioavailability, myocardial tissue oxygenation, and iNOS expression [7].
References:
[1].Elmongy E I, Alanazi W S, Aldawsari A I, et al. Antimicrobial evaluation of sulfonamides after coupling with thienopyrimidine coplanar structure[J]. Pharmaceuticals, 2024, 17(2): 188.
[2].Rettie A E, Jones J P. Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics[J]. Annu. Rev. Pharmacol. Toxicol., 2005, 45(1): 477-494.
[3]. Bogaard J, Chang Q, Berdyshev E A, et al. Cytochrome P450 2C Inhibitors Protect Photoreceptors from Light Induced Cell Death[J]. Investigative Ophthalmology & Visual Science, 2014, 55(13): 4387-4387.
Sulfaphenazole是一种磺胺类抗菌药物。它竞争性地抑制细菌二氢叶酸合酶，阻断细菌叶酸合成，从而抑制细菌生长和繁殖[1]。Sulfaphenazole是人类细胞色素P450 (CYP) 2C9酶的选择性抑制剂[2]。Sulfaphenazole是一种细胞保护剂，可防止光诱导的感光细胞死亡。Sulfaphenazole可抑制光诱导的坏死和线粒体应激引发的细胞凋亡[3]。
在酵母表达的1A、3A和2C亚家族人类细胞色素P450中，Sulfaphenazole是CYP 2C9的强效竞争性抑制剂，Ki值为0.3±0.1μM。Sulfaphenazole对CYP 2C8和2C18的Ki值分别为63μM和29μM。Sulfaphenazole对CYP 1A1、1A2、3A4和2C19无抑制作用[2]。Sulfaphenazole（10μM；1h）可使光诱导的凋亡细胞和坏死细胞数量分别减少33%和44%[3]。
在糖尿病雄性小鼠（db/db 品系）模型中，Sulfaphenazole（5.13mg/kg；po；8 weeks）可降低氧化应激（以血浆 8-异前列腺素水平衡量）、提高 NO 生物利用度（以 NO2− 衡量）并恢复 db/db 小鼠的内皮功能，且不影响血浆葡萄糖水平 [4]。在小鼠热损伤和 I/R 诱发的压力损伤模型中，损伤后给予Sulfaphenazole（100µL；ip；15d）可改善组织灌注，从而降低整体损伤严重程度、改善伤口闭合并增加疤痕拉伸强度 [5]。在大鼠心肌缺血再灌注 (I/R) 损伤模型中，Sulfaphenazole（30mg/kg；iv）预治疗可恢复心脏功能并减少心肌梗死面积。此外，Sulfaphenazole还可降低再灌注心脏中的超氧阴离子水平并提高 NO 生物利用度 [6]。在急性心肌梗死（MI）大鼠模型中，Sulfaphenazole（8.1mg/kg；ip；3d）预处理大鼠可改善I/R诱导的心肌损伤，并通过减少超氧化物的产生、过氧亚硝酸盐的形成，以及通过增强NO的生物利用度、心肌组织氧合和iNOS的表达来改善心脏收缩功能[7]。