Shikimic acid complexes of platinum. Preparation, reactivity, and antitumor activity of (R,R-1,2-diaminocyclohexane) bis(shikimato) platinum(II). Evidence for a novel rearrangement involving platinum-carbon bond formation.

Abstract

The complex (R,R-1,2-diaminocyclohexane)bis(shikimato)platinum(II) (shikimato = the anion of 3R,4S,5R-trihydroxy-1-cyclohexene-1-carboxylic acid), I, has been synthesized and purified by high performance liquid chromatography (HPLC). The complex is only moderately stable in aqueous solution. Its major hydrolysis product, also purified by HPLC, is proposed to be a unique complex type in which a single shikimate group is coordinated through both the carboxylate oxygen and the C(2) vinylic carbon of the shikimate moiety [Pt(R,R-dach)(O,C-shikimato)], II. In vitro, complex I is active against L1210 leukemia and against an L1210 cell line with acquired resistance to cisplatin. In vivo, the complex is active against L1210, P388, and B16 melanoma; this activity is highly schedule-dependent. Complex II is also active against L1210 leukemia.

• Authors: N Farrell, J D Roberts, M P Hacker
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 42 Issue 4 Pg. 237-46 (Jun 1991) ISSN: 0162-0134 [Print] United States
• PMID: 1880505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Cyclohexenes
• Organoplatinum Compounds
• Platinum
• Carbon
• 1,2-diaminocyclohexane-bis(shikimato)platinum(II)

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, therapeutic use)
• Carbon (chemistry)
• Chromatography, High Pressure Liquid
• Cyclohexenes
• Leukemia L1210 (drug therapy)
• Leukemia P388 (drug therapy)
• Magnetic Resonance Spectroscopy
• Melanoma, Experimental (drug therapy)
• Organoplatinum Compounds (chemical synthesis, chemistry, therapeutic use)
• Platinum (chemistry)