Synthesis and antitumor activity of a platinum (II)-doxorubicin complex

Zunino, Franco; Savi, Giuseppina; Pasini, Alessandro

doi:10.1007/bf00262293

Cited by 31 publications

(14 citation statements)

References 4 publications

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“…A cationic platinum (II) complex with proflavin (3,6-diaminoacridine) (29) has been designed by Ceci et al, whereby two monofunctional platinum moieties are linked to the amino groups of the dye through ethylene linkers [79]. In an recent report presenting the interactions between (29) and doubleZunino et al have synthesized and evaluated a cisplatindoxorubicine conjugate, whereby the platinum moiety was coordinated through the amino-sugar residue of the anthracycline [75]. This complex is found to exhibit pronounced tumor-inhibiting activity in various resistant solid tumor models and hemoblastoses, by virtue of combining the adduct-forming activity of cisplatin with the helical poly(A) both the platinum residues and the proflavin system have been found to intercalate and concurrently only a negligible, slow covalent binding of Pt(II) to adenine is encountered [80].…”

Section: +mentioning

confidence: 98%

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

Momekov¹,

Bakalova²,

Karaivanova

2005

CMC

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Cisplatin is an essential antineoplastic agent whose introduction in clinical use revolutionized the treatment of several solid malignancies, especially those of germinative origin. The unfavorable toxicological profile of this drug, however as well as the resistance of some common malignancies solicited the search of platinum complexes, characterized by lower toxicity and/or broader antitumor spectrum. Thus during the last three decades a plethora of several thousand platinum coordination compounds have been synthesized and evaluated as potential antineoplastic agents. Despite of the numerous compounds investigated however only few of the proved to be of clinical significance and actually none of them could be considered as an ideal substitute for cisplatin regarding both lower toxicity and broader spectrum of anticancer activity. To a great extent the platinum-based drug discovery was confined at structural modification of the parent compound in line with the classic structure-activity relationship concept. Conversely, since the majority of platinum complexes developed so far are closely related structural analogues of cisplatin, it is not surprising that they produce similar cellular effects and any altered pattern of antitumor activity and/or toxicity is likely to be due to pharmacokinetic, rather than truly mechanistic, factors. Studies over the last few years have shown that the structural resemblance to cisplatin is not an absolute requirement for cytotoxicity, which broadens the search for cisplatin analogues towards non-classical compounds with prominent structural/pharmacodynamic dissimilarity to the prototype. This review covers the major approaches to elaboration of non-classical platinum complexes with emphasis on complexes interacting with DNA in a cisplatin-dissimilar fashion and complexes with tumor-targeted cytotoxicity.

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Section: +mentioning

confidence: 98%

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

Momekov¹,

Bakalova²,

Karaivanova

2005

CMC

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“…Platinum centres have been attached to a variety of organic intercalators, including: doxorubicin [150], acridine [133,147,149], bis(naphalimide) [148], anilinoacridine [142], aminoacridine [134], phenazine [135,136,142], and proflavine [137]. The majority of studies, such as those by Denny and co-workers, have focussed on acridine and anilinoacridine [133,142,147,149].…”

Section: The Cytotoxicity Of a Variety Of Platinum And Organic Bis-mentioning

confidence: 99%

DNA Intercalators in Cancer Therapy: Organic and Inorganic Drugs and Their Spectroscopic Tools of Analysis

Wheate

Brodie²,

Collins³

et al. 2007

MRMC

205

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Since the discovery of the DNA intercalation process by Lerman in 1961 thousands of organic, inorganic octahedral (particularly ruthenium(II) and rhodium(III)) and square-planar (particularly platinum(II)) compounds have been developed as potential anticancer agents and diagnostic agents. The design and synthesis of new drugs is focused on bis-intercalators which have two intercalating groups linked via a variety of ligands, and synergistic drugs, which combine the anticancer properties of intercalation with other functionalities, such as covalent binding or boron-cages (for radiation therapy). Advances in spectroscopic techniques mean that the process of DNA intercalation can be examined in far greater detail than ever before, yielding important information on structure-activity relationships. In this review we examine the history and development of DNA intercalators as anticancer agents and advances in the analysis of DNA-drug interactions.

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“…However, due to severe side effects and other undesirable properties [1,2], there has been a decrease in the number of compounds based on the cisplatin structure. This has motivated the search for complexes presenting novel structures and promising activity, mainly those with the ability to overcome cisplatin resistance [3].…”

Section: Introductionmentioning

confidence: 99%

“…Metal coordination to biologically active molecules can be used as a strategy to enhance activity and overcome resistance. For instance, metal complexes of thiosemicarbazones are often more active than the free ligand, or even act as a vehicle for activation of the ligand as the cytotoxic agent [2,3]. The coordination chemistry of thiosemicarbazones has generated interest for their variable donor ability, structural diversity, and biological applications [4,5].…”

Section: Introductionmentioning

confidence: 99%

Platinum(II) and palladium(II) aryl-thiosemicarbazone complexes: synthesis, characterization, molecular modeling, cytotoxicity, and antimicrobial activity

Tavares

Paschoal

Motta

et al. 2014

Journal of Coordination Chemistry

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Platinum(II) and palladium(II) complexes [ML 2 ] have been isolated from reaction of K 2 PtCl 4 or K 2 PdCl 4 and ligands (L) derived from thiosemicarbazones. The complexes were characterized by elemental analysis, Raman, IR, and NMR spectroscopy. In addition, quantum mechanical calculations were used to predict their structures and spectroscopic properties. For the first time, theoretical calculations using 195 Pt NMR data were used to support the suggested structures. The results indicate that the thionic sulfur and the azomethine nitrogen are bonded to the metal ion in a trans configuration. Antibacterial activities and cytotoxicities of the complexes to B16-F10 and CT26.WT cell lines were also investigated. Some of the complexes demonstrated superior cytotoxic activity compared to cisplatin.

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Synthesis and antitumor activity of a platinum (II)-doxorubicin complex

Cited by 31 publications

References 4 publications

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

Novel Approaches Towards Development of Non-Classical Platinum-Based Antineoplastic Agents: Design of Platinum Complexes Characterized by an Alternative DNA-Binding Pattern and/or Tumor-Targeted Cytotoxicity

DNA Intercalators in Cancer Therapy: Organic and Inorganic Drugs and Their Spectroscopic Tools of Analysis

Platinum(II) and palladium(II) aryl-thiosemicarbazone complexes: synthesis, characterization, molecular modeling, cytotoxicity, and antimicrobial activity

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