Suramin structure

Schuetz A et al (2007) Structural basis of inhibition of the human NAD+ -dependent deacetylase SIRT5 by suramin. Structure 15(3) 377-389... 

Already, the virion-associated reverse transcriptase has been highlighted as a target. The RT gene has been cloned, and the gene product can be produced in large quantities. Several molecules of very diverse molecular structure, such as zidovudine, suramin, and rifabutin, have been shown to cause inhibition of the... 

Figure 3.10 Molecular structure of the sirtuin inhibitors suramin and NF675.

Structure-activity studies on suramin analogues as inhibitors of NAD( + )-dependent histone deacetylases (sirtuins). ChemMedChem, 2, 1419-1431. 

Fig. 3 Structures of acharan sulfate, dextran sulfate, suramin, pentosan polysulfate, and phosphomannopentaose sulfate (PI-88). Representative saccharide units comprising each of these polymers are shown, where n is the degree of polymerization.

For obvious reasons of structural analogy to heparinoids the focus of this review is on sulfated carbohydrate derivatives. While it is not in all cases clear that these compounds really mimic the physiological activity of heparinoids, it is even less so for non-carbohydrate sulfates or sulfonates. Examples of the latter class include suramin and the simple 1,3-propanediol disulfate. Suramin is a sulfonat-ed bis-naphthalene derivative used as a drug to treat African trypanosomiasis and onchocerciasis (a filarial infection) it was also tested in a number of other indications including adrenocortical carcinomas and AIDS. A wider use is, however, restricted by various toxic effects [66]. 1,3-Propanediol disulfate reduced inflammation-associated amyloid progression in vivo after oral administration which may be relevant to the treatment of Alzheimer s disease [67]. 

Chemical structures of reported inhibitors of HIV-1 integrase. (I) aurintricarboxylic acid monomer (II) cosalane (III) dihydronaphthoquinone or DHNQ (IV) primaquine (V) caffeic acid phenethyl ester or CAPE (VI) quercetin (VII) quercetagetin (VIII) AG1717 (IX) 3-conidendrol (X) suramin (XI) curcumin. 

Suramin (refer to Box 3.1, where the structure of this compound is shown), which was used against trypanosomes, was developed by Paul Ehrlich. It was one of the first drugs to be developed by the discovery method to cure a specific ailment. Suramin is a derivative (a variation) of a fabric dye that was found to have antiparasitical activity, (a) Would you expect suramin to undergo delocalization of electrons ... 

Trapp, J., Meier, R., Hongwiset, D., Kassack, M. U., Sippl, W., Jung, M. Structure-activity studies on suramin analogues as inhibitors of NAD(-H)-dependent histone deacetylases (sirtuins). Chem. Med. Chem. 2007, 2(10), 1419-1431. 

Figure 1. Chemical structure of PPADS (left = 2-SO3H, = 4-SO3H) and suramin...

In order to gain some insights into the structural features that contribute to the antagonistic properties of suramin at P2-purinoceptors, we have synthesized and pharmacologically characterized a series of suramin analogues (Figure 1). We hoped to alter the activity profile of suramin in favour of one of the P2-purinoceptor subtypes. 

Figure 2. Inhibitory potency of suramin and of three of its analogues (for chemical structure, see Figure 1) at P2X P2Y"Purinoceptors. — Inhibition of neurogenic contractions (0.05 Hz plCfo values) in rabbit vas deferens (P2X-receptors). -- Inhibition of ADP(3 binding (pKj values) to turkey erythrocyte membranes (P2Y- "sceptors) [35].

An early report suggested that suramin can block the nucleotide-dependent calcium pump of rabbit skeletal sarcoplasmic reticulum by inhibition of the calcium uptake and the ATTase activity [51]. These results have been confirmed by Emmik et al. [52]. Baumert and Heider [53] found that pyridoxal-5-phosphate and a series of its analogues (for chemical structure. 

The pseudo-spiro compound 31, a moderately active Sirt2 inhibitor, has been identified by an in silico approach [119]. A crystal structure of the poly-sulfony-lated symmetric urea suramin 32 bound to the catalytic site of Sirt5 has been elucidated [110] and demonstrated that the poly-aromatic compound covers the... 

Braddock, P.S., Hu, D.-E., Fan, T.-P.D., Stratford, I.J., Harris, A.L and Bicknell, R. (1994) A structure-activity analysis of antagonism of the growth factor and angiogenic activity of basic fibroblast growth factor by suramin and related polyanions. Br. J. Cancer 69 890-898. 

Reverting to trypanosomiasis, and the anionic drug, suramin 6.8), which is still much used in treating it, we note that the structure of this drug is remarkably specific in that the removal of the two methyl-groups abolishes activity... 

Figure 7.6 Effects of the stilbene derivatives DIDS, SITS, and DNDS on intracellular Ca release in A7r5 cells, (a) Chemical structure of suramin, DIDS, SITS, and DNDS.

McGeary RP, Bennett AJ, Tran QB, Cosgrove KL, Ross BP. Suramin clinical uses and structure-activity relationships. Mini Rev Med Chem. 2008 8(13) 1384—1394. 

Another example of protein-ligand binding is shown in Figure 8, which compares the DCDR spectra of the human serum albumin-suramin complex (a) and the human serum albumin control (b). The resulting difference spectrum (c) clearly reveals an intensity increase broad peak at around 1333 cm as well as other peaks that clearly resemble those of the suramin control sample (d). In this case, as with the lysozyme-nitrate complex, there is again no evidence of significant suramin induced protein secondary structure change. 

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