Suramin|145-63-1|安捷凯

Background

Suramin is a polysulfonated naphthylurea with antiviral, antiparasitic, and anticancer activities.¹ It is negatively charged at physiological pH and therefore binds to various intracellular targets including, but not limited to, ryanodine receptor 1 (IC₅₀ = 4.9 ?M), G protein-coupled receptors, P₂ purinergic receptors, PDGF, PKC, transferrin, DNA and RNA polymerases, sirtuins, and various cytokines.^1,2,3 It reduces Zika virus infectivity in Vero cells (IC₅₀ = ^~2.5-5 ?g/ml).⁴ In vivo, suramin induces cell cycle arrest at the G₂/M phase and apoptosis in L. donovani promastigotes in vitro and reduces hepatic parasitic burden in a mouse model of L. donovani-induced visceral leishmaniasis.⁵ Suramin (60 mg/kg) reduces tumor volume in patient-derived xenograft (PDX) mouse models of malignant mesothelioma.⁶ Formulations containing suramin have been used in the treatment of African sleeping sickness.

1.Wiedemar, N., Hauser, D.A., and M?ser, P.100 years of suraminAntimicrob. Agents Chemother.64(3)e01168-01119(2020) 2.Klinger, M., Bofill-Cardona, E., Mayer, B., et al.Suramin and the suramin analogue NF307 discriminate among calmodulin-binding sitesBiochem. J.355(3)827-833(2001) 3.Charlton, S.J., Brown, C.A., Weisman, G.A., et al.PPADS and suramin as antagonists at cloned P2Y- and P2U- purinoceptorsBr. J. Pharmacol.118(3)704-710(1996) 4.Tan, C.W., Sam, I.-C., Chong, W.L., et al.Polysulfonate suramin inhibits Zika virus infectionAntiviral Res.143186-194(2017) 5.Khanra, S., Juin, S.K., Jawed, J.J., et al.In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasisPLoS Negl. Trop. Dis.14(8)e0008575(2020) 6.Chahinian, A.P., Mandeli, J.P., Gluck, H., et al.Effectiveness of cisplatin, paclitaxel, and suramin against human malignant mesothelioma xenografts in athymic nude miceJ. Surg. Oncol.67(2)104-111(1998)

Protocol

Kinase experiment:

The ATPase assay is performed in a 10 μL reaction mixture containing 20 mM Tris-HCl (pH 7.5), 1 mM DTT, 8 mM MgCl2, 5 μM M13 circular ssDNA, 2.5 μM RecA from the specified bacterial species and increasing concentrations of suramin. The reaction is initiated by the addition of 2 mM [α-32P]ATP, incubated for 30 min at 37°C and stopped by the addition of 25 mM EDTA[2].

Animal experiment:

Rats: To assess the potential preventive and curative effects of suramin, rats are randomly divided into four groups after MCT injection. In the preventive strategy, the treatment is started on the first day, and one group receives 10 mg/kg suramin intravenously twice weekly for 3 weeks, while a second group receives only the vehicle at the same time points. To assess the potential curative effects of suramin, rats are given MCT and are left untreated for 21 days before being randomly divided into two groups that are subsequently treated with either suramin or vehicle from day 21 to day 42 inclusive. The effect of suramin on survival is evaluated from the day 21 of MCT injection to day 42 corresponding to the treatment period[4].

参考文献:

[1]. Jindal HK, et al. Suramin affects DNA synthesis in HeLa cells by inhibition of DNA polymerases. Cancer Res. 1990 Dec 15;50(24):7754-7.
[2]. Nautiyal A, et al. Suramin is a potent and selective inhibitor of Mycobacterium tuberculosis RecA protein and the SOS response: RecA as a potential target for antibacterial drug discovery. J Antimicrob Chemother. 2014 Jul;69(7):1834-43.
[3]. Bojanowski K, et al. Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcomacells. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3025-9.
[4]. Izikki M, et al. The beneficial effect of suramin on monocrotaline-induced pulmonary hypertension in rats. PLoS One. 2013 Oct 15;8(10):e77073.
[5]. J Biol Chem. 1999 Jul 2;274(27):18997-9002.Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5.

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Suramin

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Background

Protocol

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