Platinum complexes antitumor activity

Complexes with this formulation satisfy the generally accepted criteria for structural features required in an antitumor-active platinum complex, but are expected to possess kinetic advantages when compared to the prototype antitumor platinum complex, cis-dichloro-diamineplatinum (II). Complexes have been prepared where L is a monoprotonated diamine and also where L is a protonated amino-olefin. All complexes have been examined for cytotoxicity against L1210 leukemia in cell culture, and selected compounds have been tested for antitumor activity vivo (LI210 leukemia in BDF mice). One compound, where L is protonated 3-amino-quinuclidine, has significant vivo activity, with T/C approaching 150%. 

VII. Antitumor Active Platinum-Blue Complexes References... 

A pivotal feature of the preclinical lead discovery process for identifying orally active platinum complexes was a comparison of antitumor activity in mice bearing the ADJ/PC6 subcutaneous murine plasmacytoma by the oral vs. intraperitoneal (i.p.) routes of administration. The ADJ/PC6 tumor model had been widely used in earlier platinum drug development pro-... 

Perez-Soler, R., Han, I., Al-Baker, S., Khokhar, A. R., 1994, Lipophihc platinum complexes entrapped in liposomes improved stability and preserved antitumor activity with complexes containing linear alkyl carboxylate leaving groups. Cancer Chemother. Pharmacol. 33 378-384. 

Bloemink MJ, Diederen JJH, Dorenbos JP et al (1999) Calcium ions do accelerate the DNA binding of new antitumor-active platinum aminophosphonate complexes. Fur J Inorg Chem 1655-1657... 

Salts of neodecanoic acid have been used in the preparation of supported catalysts, such as silver neodecanoate for the preparation of ethylene oxide catalysts (119), and the nickel soap in the preparation of a hydrogenation catalyst (120). Metal neodecanoates, such as magnesium, lead, calcium, and zinc, are used to improve the adherence of plasticized poly(vinyl butyral) sheet to safety glass in car windshields (121). Platinum complexes using neodecanoic acid have been studied for antitumor activity (122). Neodecanoic acid and its esters are used in cosmetics as emoUients, emulsifiers, and solubilizers (77,123,124). Zinc or copper salts of neoacids are used as preservatives for wood (125). 

The electronic spectra and magnetic susceptibility of [Ni(21)Cl2] were found to be consistent with a five-coordinate high spin complex. This complex has greater antitumor activity against P388 lymphocytic leukemia test system in mice than cobalt(II), copper(II), zinc(II) and platinum(II) complexes of 21 [187],... 

Since the discovery of the anticancer and antitumor activity of platinum complexes, there has been an effort to identify organic complexes of other metals that possess similar activities. Gielen and coworkers39 state that the antitumor activities of the di- -butyltin(TV) and diethyltin(IV) fluorobenzoates (FQdECOO SnlG and (FC6H4-C00SnR2)402, R = Et, Bu are satisfactory. 

Nonsymmetrical ligand substitution reactions also play an important role in a number of biological processes. One of these concerns the antitumor activity of platinum metal complexes, for which substitution processes involving DNA moieties are generally accepted to... 

The greatest research effort on radiation sensitizers has focused on organic compounds however, platinum complexes conform to the hypotheses for radiation sensitizers since they are electron affinic and react preferentially with the hydrated electron in aqueous solution. Early studies of cisplatin in combination with radiation therapy suggested a synergistic effect in antitumor activity (50,51). Much of the initial data were obtained using cells in tissue culture (52), these data indicated that the potential of cisplatin to inhibit repair of radiation-induced damage to DNA could be an important contributor to the enhanced tumor cell killing seen in vivo by the combination of these two modes of treatment. 

Although there has heen a great deal of research concerning how platinum(II) complexes hind to biological molecules and the hkely mechanism of antitumor activity of these platinum-containing species, far less attention has heen paid to the properties of other metal complexes in this arena. Recent attention has fallen on cohalt(II)-Schiff hase complexes, as several have heen discovered to have promise as antiviral agents. A review of recent work has appeared elsewhere [64], so the topic will not he covered here however, in addition to focusing on recent developments, emphasis is placed on the introduction of the new head unit, 3,6-diformylpyridazine (13), into Schiff-hase macrocyclic electrochemistry. 

Pinacolone, o-(diphenylphosphino)benzoyl-coordination chemistry, 401 Piperidine, IV-hydroxy-metal complexes, 797 pA a values azole ligands, 77 Plant roots amino acids, 962 carboxylic acids, 962 Plastocyanin copper binding site, 557 copper(II) complexes, 772 copper(II) site in, 770 Platinum, dichlorobis(benzonitrile)-IR spectrum, 264 Platinum, cis-dichlorodianunine-antitumor activity, 34, 979 Platinum, ethylenebis(triphenylphosphine)-reactions with 5,6-dimethyl-2,l,3-benzothiadiazole, 194 Platinum blue formation, 265 Platinum complexes acetylacetone reactions, 380 amides, 491 amidines... 

Most platinum compounds exist as coordination complexes the tetravalent compounds typically are more toxic than the hexavalent ones [10]. Certain neutral platinum complexes exhibit antitumor activity and therefore are used in chemotherapy drugs such as cisplatin. Speeiation is required to distinguish platinum chemotherapy drugs from their metabolites in patients blood and serum samples. 

Ruiz J, Cutillas N, Vicente C, Villa MD, Lopez G, Lorenzo J, Aviles FX, Moreno V, Bautista D (2005) New palladium(II) and platinum(II) complexes with the model nucleobase 1-methylcytosine antitumor activity and interactions with DNA. Inorg Chem 44 ... 

Ruiz J, Villa MD, Cutillas N, Lopez G, de Haro C, Bautista D, Moreno V, Valencia L (2008) Palladium(II) and Platinum(II) Organometallic Complexes with 4, 7-dihydro-5-methyl-7-oxo[l, 2, 4]triazolo[l, 5-a]pyrimidine. Antitumor activity of the platinum compounds. Inorg Chem 47 4490 1505... 

We certainly do not intend these rules to restrict future research, but only to encompass a large amount of past experience with platinum(II) complexes. Obviously exceptions will, and have already, occurred. For example, the high activity of bidentate leaving groups such as oxalate and malo-nate (see structures of Fig. 4) first synthesized by M. Cleare and J. Hoe-schele in this laboratory are not encompassed nor is the effect of cyclic amines, developed by Tobe, which decrease the solubility of the complexes, but markedly enhance the antitumor activity. Here, studies of the rela-... 

Since the discovery of the antitumor activity of m-PtCNFhuC (cisplatin, cd-DDP) by Rosenberg et al. [1], the interactions of cisplatin with nucleotides and nucleobases have attracted attention towards gaining an understanding of the mechanism of the antitumor activity of cisplatin at a molecular level. In the course of such studies, dark-blue platinum complexes called platinum blues were obtained when hydrolysis products of cis-... 

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