Thirty Years of the Drug Candidate NAMI-A and the Myths in the Field of Ruthenium Anticancer Compounds: A Personal Perspective

被引:332
作者
Alessio, Enzo [1 ]
机构
[1] Univ Trieste, Dept Chem & Pharmaceut Sci, Via L Giorgieri 1, I-34127 Trieste, Italy
关键词
Medicinal chemistry; Drug discovery; Antitumor agents; Biological activity; Ruthenium; X-RAY-STRUCTURE; IN-VITRO CYTOTOXICITY; HUMAN SERUM-ALBUMIN; CELL LUNG-CANCER; CISPLATIN BINDING-SITES; ANTITUMOR-ACTIVITY; DNA-BINDING; PROTEIN INTERACTIONS; CYCLORUTHENATED COMPOUNDS; HETEROCYCLIC COMPLEXES;
D O I
10.1002/ejic.201600986
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
As anticipated in the title, this contribution is basically divided into two, strictly connected, parts. The first is a personal overview of the ruthenium drug candidate NAMI-A, almost 30 years after its synthesis and the discovery of its unprecedented antimetastatic properties in animal models at nontoxic dosages. The sections relating to the chemical and biological behavior of the complex, and the hypotheses on its mechanism(s) of action, are kept to a minimum, whereas more space is devoted to discussion of the results of the clinical investigations. The second part deals in detail with a number of undemonstrated misconceptions ( or myths) that, over the years, have thrived around NAMI-A and other ruthenium drug candidates, thus negatively affecting the whole field of Ru anticancer drugs.
引用
收藏
页码:1549 / 1560
页数:12
相关论文
共 162 条
[41]   COMPARISON OF CISPLATIN AND CARBOPLATIN CYTOTOXICITY IN HUMAN OVARIAN-CANCER CELL-LINES USING THE MTT ASSAY [J].
FANNING, J ;
BIDDLE, WC ;
GOLDROSEN, M ;
CRICKARD, K ;
CRICKARD, U ;
PIVER, MS ;
FOON, KA .
GYNECOLOGIC ONCOLOGY, 1990, 39 (02) :119-122
[42]   Library of second-generation cycloruthenated compounds and evaluation of their biological properties as potential anticancer drugs: Passing the nanomolar barrier [J].
Fetzer, Ludivine ;
Boff, Bastien ;
Ali, Moussa ;
Meng Xiangjun ;
Collin, Jean-Paul ;
Sirlin, Claude ;
Gaiddon, Christian ;
Pfeffer, Michel .
DALTON TRANSACTIONS, 2011, 40 (35) :8869-8878
[43]  
Frausin F, 2005, J PHARMACOL EXP THER, V313, P227, DOI 10.1124/jpet.104.078352
[44]   Tumour cell uptake of the metastasis inhibitor ruthenium complex NAMI-A and its in vitro effects on KB cells [J].
Frausin, F ;
Cocchietto, M ;
Bergamo, A ;
Searcia, V ;
Furlani, A ;
Sava, G .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2002, 50 (05) :405-411
[45]  
GARZON FT, 1987, CANCER CHEMOTH PHARM, V19, P347
[46]   Inhibition of B16 melanoma metastases with the ruthenium complex imidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate and down-regulation of tumor cell invasion [J].
Gava, B ;
Zorzet, S ;
Spessotto, P ;
Cocchietto, M ;
Sava, G .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 317 (01) :284-291
[47]   A categorization of metal anticancer compounds based on their mode of action [J].
Gianferrara, Teresa ;
Bratsos, Ioannis ;
Alessio, Enzo .
DALTON TRANSACTIONS, 2009, (37) :7588-7598
[48]   Structure-activity relationships for NAMI-A-type complexes (HL)[trans-RuCl4L(S-dmso)ruthenate(III)] (L = imidazole, indazole, 1,2,4-triazole, 4-amino-1,2,4-triazole, and 1-methyl-1,2,4-triazole):: Aquation, redox properties, protein binding, and antiproliferative activity [J].
Groessl, Michael ;
Reisner, Erwin ;
Hartinger, Christian G. ;
Eichinger, Rene ;
Semenova, Olga ;
Timerbaev, Andrei R. ;
Jakupec, Michael A. ;
Arion, Vladimir B. ;
Keppler, Bernhard K. .
JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (09) :2185-2193
[49]   Anti-tumour activity in non-small cell lung cancer models and toxicity profiles for novel ruthenium(II) based organo-metallic compounds [J].
Guichard, SM ;
Else, R ;
Reid, E ;
Zeitlin, B ;
Aird, R ;
Muir, M ;
Dodds, M ;
Fiebig, H ;
Sadler, PJ ;
Jodrell, DI .
BIOCHEMICAL PHARMACOLOGY, 2006, 71 (04) :408-415
[50]   Structure-activity relationships for cytotoxic ruthenium(II) arene complexes containing N,N-, N,O-, and O,O-chelating ligands [J].
Habtemariam, Abraha ;
Melchart, Michael ;
Fernandez, Rafael ;
Parsons, Simon ;
Oswald, Iain D. H. ;
Parkin, Andrew ;
Fabbiani, Francesca P. A. ;
Davidson, James E. ;
Dawson, Alice ;
Aird, Rhona E. ;
Jodrell, Duncan I. ;
Sadler, Peter J. .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (23) :6858-6868