Suramin analogues

A. R. Gagliardi, M. Kassack, A. Kremeyer, G. Muller, P. Nickel, and D. C. Collins. Antiangiogenic and antiproliferative activity of suramin analogues. Cancer Chemother. Pharmacol. 41 117-124 (1998). 

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

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. 

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. 

Taken together, the results confirm that the parent compound, suramin, does not differentiate between P2X" P2Y receptor-mediated events. In contrast, the suramin analogue, NF023, is a specific P2-purinoceptor antagonist showing a high selectivity for the P2X-subtype. 

Fleck SL, Birdsall B, Babon J, Dluzewski AR, Martin SR, Morgan WD, Angov E, Kettleborough CA, Feeney J, Blackman MJ, Holder AA, Suramin and suramin analogues inhibit merozoite surface protein-1 secondary processing and erythrocyte invasion by the malaria parasite Plasmodium falciparum, J. Biol. Chem. 2003 278 47670-47677. 

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. 

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