New antitumour active platinum compounds containing carboxylate ligands in trans geometry: synthesis, crystal structure and biological activity

Abstract

New asymmetric trans-platinum(II) complexes, composed of an isopropylamine, an azole and two carboxylate leaving groups, are presented. The crystal and molecular structures of one of the complexes has been determined and the cytotoxicity and reactivity with 5 -guanosine monophosphate is reported. The complexes show a reduced reactivity, but no decrease in cytotoxic activity compared to their chloro-counterparts. Furthermore the complexes largely overcome cisplatin resistance, they therefore present an interesting class of antitumour active trans-platinum complexes.

Structure-cytotoxicity relationship for different types of mononuclear platinum(II) complexes with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine

“…Additionally, the induced drug resistance to cells and its low aqueous solubility has restricted the application of this drug. These clinical inconveniences in cisplatin chemotherapy prompted the design and synthesis of more effective and less toxic platinum-based anticancer drugs [5][6][7][8]. Consequently, new platinum drugs with equal or greater antitumor activity but lower toxicity have been developed by replacing the labile chloride and stable amine ligands with other leaving groups such as cyclic and acyclic amines.…”

Robust Structure and Reactivity of Aqueous Arsenous Acid–Platinum(II) Anticancer Complexes

“…In general, hydrolysis of Pt-Cl bonds is slow (t 1/2 = 2h at 37°C and 4 mM Cl − ) [22] and rapid substitution usually requires addition of reagents such as AgNO 3 . The substitution of the Cl − ligand in 1 with SCN − in water occurs immediately at room temperature likely driven by the trans effect of the arsenic moiety [23] .…”

Kinetic and thermodynamic studies on reactions of [PtCl(bpma)]+ and [Pt(bpma)H2O]2+ (bpma = bis-(2-pyridylmethyl)amine) with some azoles and diazines

“…Derivatives based on triazole, pyridazine and pyrazole can also show antibacterial effects [7]. Some antitumor active complexes of Pt(II) have azoles or diazines in their structures [8], also azoles and diazines are often used as bridging ligands in the synthesis of dinuclear Pt(II) complexes [3,4].…”