Development of selectively acting platinum complexes

Schönenberger, Helmut; Wappes, B.; Jennerwein, Margaretha; Berger, Martin R.

doi:10.1016/0305-7372(84)90051-3

Cited by 10 publications

(2 citation statements)

References 2 publications

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“…Kidani's group have reported [35] the activity of a series of 1,2-diphenylethylenediamine complexes analogous to the antioestrogen models by Schoenenberger [106][107][108]. The platinum (II) halide complexes were water insoluble and demonstrated no activity in the L1210 screen.…”

Section: Chelating Diaminesmentioning

confidence: 99%

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Advances in platinum cancer chemotherapy

Hydes

Russell

1988

Cancer Metast Rev

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In the past 4 years substantial progress has been made in the development of platinum cancer chemotherapy. A number of drug candidates have undergone clinical trials and one 'second generation' platinum drug, carboplatin, has been approved for use in the treatment of ovarian and small cell lung cancer. This review covers the major developments since the last international conference on Platinum Chemotherapy in Vermont, and attempts to highlight the primary factors that appear to be influencing the synthesis and screening of potential third generation platinum drugs. A predominant feature in the evaluation of analogues has been the emphasis on chelating diamine complexes, in particular those of diaminocyclohexane, which show activity in L1210 tumours that are resistant to cisplatin, and the use of a wide range of carboxylate ligands as a means of circumventing solubility and toxicity problems inherent in the parent compounds. There has also been an increased effort in studies relating to complexes containing mixed amines and functionalised amines, building on the assumption, which remains valid to date, that two amines are a necessary requirement for anti-tumour activity. Efforts have also been made to address the use of complexes containing biologically active ligands, and the concept of targeting compounds to specific organs and formulating drugs to achieve more specific activity or controlled release of drugs with lower toxicities. These may provide a viable route to drugs that can be administered more easily, for example by an oral route, or show a different spectrum of activity. However, it may prove difficult to adequately characterise these more complex systems. The major problem encountered in evaluating cisplatin analogues, as with other prospective cancer drugs, is finding reproducible anti-tumour screens that are predictive of the behaviour of the drugs in the clinic. Progress is being made in the development of sensitive and resistant human tumour xenograft lines and this area should be monitored with interest, as it may provide a key to the development of a future platinum drug, hopefully with a wider range of activity than either cisplatin or carboplatin.

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Section: Chelating Diaminesmentioning

confidence: 99%

“…The authors concluded that higher oestrogen receptor affinity is a necessary requirement for a viable drug [106][107][108]. In order to achieve activity, particularly in tumours that are refractory to platinum, toxicity or high dose levels are a necessary compromise unless an added degree of selectivity can be conferred on the molecule.…”

Section: Targetingmentioning

confidence: 99%

Advances in platinum cancer chemotherapy

Hydes

Russell

1988

Cancer Metast Rev

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Neue Cisplatin-Analoga — auf dem Weg zu besseren Cancerostatica

Pasini

Zunino²

1987

Angew. Chem.

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Der klinische Erfolg von Cisplatin (cis-Diammindichloroplatin(1l)) bei der Chemotherapie von Tumoren ermutigte zur Suche nach Analoga mit geringerer Toxizitat, besserem therapeutischem Index und hoherer Wirksamkeit. Buchstablich Tausende von Analoga, durch Austausch der Ammin-und der Chloroliganden durch andere Amine bzw. anionische Liganden erhalten, wurden in experimentellen Tumormodellen systematisch auf Aktivitat gepriift. Einige dieser Analoga wurden fur klinische Tests ausgewahlt, aber nur sehr wenige scheinen vielversprechende Antitumorwirkstoffe zu sein. Bei der planvollen Entwicklung und Synthese neuer Cisplatin-Analoga in jiingerer Zeit IieR man sich unter anderem von folgenden Uberlegungen leiten: 1) Durch Platinkomplexe rnit Tragermolekiilen als Liganden sollte eine erhohte Wirkstoffkonzentration im Tumorgewebe zu erreichen sein; 2) Platinkomplexe mit Chemotherapeutica als Liganden konnten als polyfunktionelle Arzneimittel synergistische Wirkungen entfalten; 3) Komplexe mit mehr als einem Platinatom konnten wirksarner als Kornplexe mit einem Platinatom sein; 4) Platinkomplexe konnten als Sensibilisatoren bei der Strahlentherapie eingesetzt werden. In diesem Beitrag werden wir nach einer kurzen Betrachtung der ,,traditionellen" Analoga die unseres Erachtens erfolgversprechendsten Wege zu neuartigen Cisplatin-Analoga diskutieren.

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New Cisplatin Analogues—On the Way to Better Antitumor Agents

Pasini

Zunino

1987

Angew. Chem. Int. Ed. Engl.

200

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The clinical success of cisplatin (cis-diamminedichloroplatinum(1r)) in antitumor chemotherapy has encouraged an all-out search for analogues with lower toxicity, improved therapeutic index and increased activity. Literally thousands of analogues, obtained by replacement of the ammine-and chloro-ligands by other amines and anionic ligands, respectively, have been systematically screened for activity in experimental tumor models. Some of these analogues have been selected for clinical evaluation, but only very few of them appear to be promising antitumor agents. More recently, cisplatin analogues have been designed and synthesized on the basis of, inter alia, the following considerations: 1) platinum complexes with carrier molecules as ligands should prove useful for achieving increasing drug concentration in tumor tissues; 2) platinum complexes with chemotherapeutic agents as ligands could afford polyfunctional drugs with synergistic action; 3 ) complexes containing more than one platinum atom might be more effective than complexes containing only one platinum atom; 4) platinum complexes could be used as sensitizers in radiation therapy. In this paper, we shall give a brief account of the "traditional" analogues, and then critically discuss what we believe could be the new trends in the design of cisplatin analogues.

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Development of selectively acting platinum complexes

Cited by 10 publications

References 2 publications

Advances in platinum cancer chemotherapy

Advances in platinum cancer chemotherapy

Neue Cisplatin-Analoga — auf dem Weg zu besseren Cancerostatica

New Cisplatin Analogues—On the Way to Better Antitumor Agents

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