Unusual Dimeric Chemical Structure for a Carboplatin Analogue as a Potential Anticancer Complex

Abstract

An unexpected and unusual dimeric platinum(II) tetracarboxylate complex was obtained by the reaction of cis-[Pt(NH(3))(2)I(2)] with disilver dicarboxylate. The complex exhibits greater in vitro anticancer activity and lower toxicity in mice than its parent compound, carboplatin, and is therefore worthy of further evaluation as a potential antitumor dinuclear platinum agent.

Potent Anticancer Activity and Possible Low Toxicity of Platinum(II) Complexes with Functionalized 1,1‐Cyclobutanedicarboxylate as a Leaving Ligand

“…To study the toxicity of the compounds in vivo, acute toxicity of DN603 and DN604 was first tested by establishing the range of doses of the compound that caused 0 and 100 % death rates for mice. The LD 50 values of DN603 and DN604 were 100.3 and 150.1 mg kg −1 , respectively, which are remarkably greater than the reported value for cisplatin 34. 35 Particularly, the acute toxicity of DN604 is even less than that of carboplatin (Table 3).…”

“…The LD 50 values of DN603 and DN604 were 100.3 and 150.1 mg kg À1 , respectively, which are remarkably greater than the reported value for cisplatin. [34,35] Particularly, the acute toxicity of DN604 is even less than that of carboplatin (Table 3). Further studies on the acute toxicity of DN604 together with carboplatin and cisplatin as contrasts were also conducted with rats.…”

Synthesis and anticancer activity of a new water-soluble derivative of heptaplatin, cis-{Pt(II)[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane](3-acetoxyl-cyclobutane-1,1-dicarboxylato)}

“…The diaminediiodoplatinum(II), as a key intermediate, was prepared as published in the literature [11]. Briefly, K 2 PtCl 4 (5 g, 12 mmol) was mixed at 45°C with KI (12 g, 6 9 12 mmol) in 100 ml H 2 O for 2 h, and then the diamine ligand (L) (2.09 g, 12 mol) was dropwise added with vigorous stirring.…”

“…3-hydroxycyclobutane-1,1-dicarboxylic acid (H 2 X) and (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane (L) were synthesized as previously described [11,12], whereas other reagents are commercially available and were used without any further purification. Chemical content for C, H, and N was analyzed using a Carlo-Erba Instrument, and platinum content was determined according to the method in USP24.…”

Inorganic pharmaceuticals

“…134 Other cytotoxic platinum(II)-containing compounds were also reported, including the co-delivery of such compounds into cancer cells. [135][136][137][138][139][140][141] There was an interesting report of the 1.77-A resolution X-ray crystal structure of a dodecamer DNA duplex with the sequence 5 0 -CCTCTGGTCTCC-3 0 that was modified to contain a single engineered 1,2-cis-(Pt(NH 3 ) 2 ) 2+ -d(GpG) cross-link, the major DNA adduct of cisplatin. 7 These data represented a significant improvement in resolution over the previously published 2.6-A structure.…”