Synthesis of Pt(II) complexes containing D-glucuronate, D-gluconate, or their acetyl derivatives and evaluation of antitumor activity against murine leukemia L1210.

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

“…Simple monosaccharides derivatized with a carboxylic function, such as gluconic, glucuronic and galacturonic acid, were coordinated to cisplatin-like substrates and evaluated for anticancer activity in vitro and in vivo, but outcomes were below expectations [74]. On the contrary, functionalization of the malonato ligand of carboplatin provided insights into the mode of action of this class of glyco-platinum conjugates.…”

Carbohydrate Complexes of Platinum-Group Metals

“…Cisplatin-type complexes [Pt(O 2 CR ch ) 2 L 2 ] ( 162 ) (L = NH 3 , 1 / 2 dach, ...) with sugar acids R ch CO 2 H as the anionic leaving groups have been synthesized via conventional methodes, such as reactions (i) of [PtL 2 (H 2 O) 2 ] 2+ with MO 2 CR ch (M = Na, K), (ii) of [PtCl 2 L 2 ] with AgO 2 CR ch or Ag 2 SO 4 /Ba(O 2 CR ch ) 2 , and (iii) of [Pt(OOC−COO)L 2 ] with Ca(O 2 CR ch ) 2 . Complexes from all three major types of sugar acids are known, namely, from aldonic acids (gluconate, tetra- O -acetylgluconate, hexahydroxyheptanoate) 116,117,118 and uronic acids (glucuronate, galacturonate, tetra- O -acetylglucuronate). ,,,, Aldaric acids HO 2 C−(CHOH) n - 2 −CO 2 H form 1:1 complexes [Pt(O 2 C−R ch −CO 2 )L 2 ] (163 ) (saccharate, mucate, tartrate) and 2:1 complexes [Pt(O 2 C−R ch −CO 2 H) 2 L 2 ] ( 164 ) (saccharate, saccharatolactone). ,,120f, From IR and 1 H NMR measurements, it was determined that the sugar coordination occurs monodentately via the negatively charged carboxylate oxygen atom in trans complexes trans -[Pt(O 2 CR ch ) 2 (NH 3 ) 2 ] ( 165 ‘) and bidentately in cis -[Pt(O 2 CR ch )(NH 3 ) 2 ](O 2 CR ch ) ( 165 ‘ ‘) (HO 2 CR ch , glucuronic acid, gluconic acid) through carboxylate oxygen atoms or through one carboxylate oxygen atom and pyranose ring oxygen atom (glucuronate anion) and α-hydroxy group (gluconate anion), respectively, forming five-membered chelate rings 116b…”