Sinefungin is a natural nucleoside antibiotic analog of S-adenosylmethionine that inhibits the activity of various methyltransferases (including protein, DNA, and RNA methyltransferases)[1-2]. Sinefungin can be used to explore epigenetic mechanisms and to support research in the development of antiviral, antiparasitic, and antifungal drugs[3-4].
In vitro, Sinefungin (10μM) applied to mouse L cells pre-infected with Newcastle disease virus and vaccinia virus for 72 hours significantly inhibited the formation of viral plaques[5]. Pretreatment of Candida albicans (C. albicans) strains with Sinefungin (0.25–4μM) for 5 days markedly inhibited hyphal elongation and long-term biofilm formation. Co-incubation of HEK293T and H1299 cells with C. albicans in the presence of Sinefungin for 2 hours reduced the ability of C. albicans to infect cells[6].
In vivo, pretreatment of mice with Sinefungin (10mg/kg/day) via intraperitoneal injection for 5 days, followed by induction of cardiac ischemia/reperfusion (I/R) model (left anterior descending coronary artery ligation for 45 minutes, reperfusion for 24 hours), significantly improved cardiac function (increased ejection fraction and fractional shortening), reduced myocardial infarct size, and lowered serum lactate dehydrogenase (LDH) levels[7]. Pretreatment of peritoneal fibrosis model C57/BL6 mice with Sinefungin (10mg/kg) via subcutaneous injection (once daily, 5 days/week for 3 weeks), significantly suppressed the increase in peritoneal cell density and thickening of the subperitoneal compact zone[8].
References:
[1] Neal RA, Iwobi MV, Robert-Gero M. Antileishmanial effect of free and encapsulated sinefungin against Leishmania donovani infections in BALB/c mice. C R Acad Sci III. 1989;308(18):485-8.
[2] Dube DK, Mpimbaza G, Allison AC, et al. Antitrypanosomal activity of sinefungin. Am J Trop Med Hyg. 1983 Jan;32(1):31-3.
[3] Bachrach U, Schnur LF, El-On J, et al. Inhibitory activity of sinefungin and SIBA (5'-deoxy-5'-S-isobutylthio-adenosine) on the growth of promastigotes and amastigotes of different species of Leishmania. FEBS Lett. 1980 Dec 1;121(2):287-91.
[4] Sala L, Franco-Valls H, Stanisavljevic J, et al. Abrogation of myofibroblast activities in metastasis and fibrosis by methyltransferase inhibition. Int J Cancer. 2019 Dec 1;145(11):3064-3077.
[5] Pugh CS, Borchardt RT, Stone HO. Sinefungin, a potent inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral multiplication. J Biol Chem. 1978 Jun 25;253(12):4075-7.
[6] Nayak A, Khedri A, Chavarria A, et al. Sinefungin, a natural nucleoside analog of S-adenosyl methionine, impairs the pathogenicity of Candida albicans. NPJ Antimicrob Resist. 2024;2(1):23.
[7] Yu ST, Sun ZY, Li N, et al. Mettl1 knockdown alleviates cardiac I/R injury in mice by inactivating the Mettl1-CYLD-P53 positive feedback loop. Acta Pharmacol Sin. 2025 Mar;46(3):592-605.
[8] Tamura R, Doi S, Nakashima A, et al. Inhibition of the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis. PLoS One. 2018 May 3;13(5):e0196844.
Sinefungin是一种S-腺苷甲硫氨酸类似物的天然核苷类抗生素，可抑制多种甲基转移酶（包括蛋白、DNA和RNA甲基转移酶）的活性[1-2]。Sinefungin可用于探索表观遗传学机制，以及开发抗病毒、抗寄生虫和抗真菌药物方面的研究[3-4]。
在体外，Sinefungin (10μM)作用于预感染纽卡斯尔病病毒和痘苗病毒的小鼠L细胞72小时，能显著抑制病毒斑块的形成[5]。Sinefungin（0.25–4μM）预处理白色念珠菌（C. albicans）菌株5天。Sinefungin显著抑制C. albicans的菌丝伸长和长期生物膜形成。Sinefungin与C. albicans共孵育HEK293T和H1299 2h，可降低C. albicans对细胞的感染能力[6]。
在体内，Sinefungin（10mg/kg/day）通过腹腔注射预处理小鼠5天，随后建立心脏缺血/再灌注（I/R）模型（左前降支冠状动脉结扎45分钟，再灌注24小时）。Sinefungin显著改善心脏功能（提高射血分数和缩短分数），减小心肌梗死面积，并降低血清乳酸脱氢酶（LDH）水平[7]。Sinefungin（10mg/kg）通过皮下注射预处理腹膜纤维化C57/BL6小鼠（每日一次，连续5天/周，持续3周）。Sinefungin显著抑制腹膜细胞密度增加和腹膜下致密区增厚[8]。