Iron and haem complexation studies of 2,3-dihydro-1H-imidazo(1,2-b)pyrazole (IMPY, NSC 51143), a tumour cell ribonucleotide reductase inhibitor. 1986

M T Ahmet, and K T Douglas, and J Silver, and A J Goddard, and D E Wilman
Department of Chemistry, University of Essex, Colchester, UK.

Spectrophotometric studies have been undertaken of the interaction of various iron-based systems with the anti-tumour agent, 2,3-dihydro-1H-imidazo(1,2-b)pyrazole (IMPY, NSC (51143), a ribonucleotide reductase inhibitor. No evidence was obtained of direct complexation in aqueous media at 25 degrees C between IMPY and Fe2+ (aq) (pH 1.5-6.8) or Fe3+ (aq) (pH 1.0-3.5), nor with a mu-oxo-bridged iron dimer (Fe--O--Fe) system. There was definitive spectral evidence of complexation of IMPY with protoporphyrin IX iron (II) at pH 7.4 and 12.9 both in the absence and presence of carbon monoxide bound at the haem-iron site. Binding of IMPY to protoporphyrin IX iron (III), in contrast, was not detected. Binding between IMPY and various iron sites important in biochemistry is discussed briefly, especially in relation to the structural properties of IMPY (from X-ray data) and the Fe--O--Fe bridge system in ribonucleotide reductase and model systems. The difficulties of the use of free heterocyclic nitrogenous bases in medicinal chemistry are discussed.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D006418 Heme The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. Ferroprotoporphyrin,Protoheme,Haem,Heme b,Protoheme IX
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D012264 Ribonucleotide Reductases Ribonucleotide Reductase,Reductase, Ribonucleotide,Reductases, Ribonucleotide
D013053 Spectrophotometry The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.

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