Synthesis, physicochemical and in vitro pharmacological investigation of new platinum (II) complexes with some cycloalkanespiro-5′-hydantoins

Bakalova, Adriana; Buyukliev, Rossen; Momekov, Georgi; Ivanov, D.; Todorov, D.; Konstantinov, Spiro; Karaivanova, Margarita

doi:10.1016/j.ejmech.2005.01.009

Cited by 25 publications

(12 citation statements)

References 9 publications

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“…Interestingly (28) elicits identical activity as cisplatin against the bcl-2 expressing DOHH-2 lymphoma, while reaching even superior cytotoxic effects at the higher concentrations. Furthermore (28) is found to induce apoptosis in HL-60 cells as evidenced by the DNA fragmentation [74]. Recent data in progress show that (28) induces far less pronounced detrimental effects in vitro upon cultured neurones, renal epithelial cells and bone marrow cells, than the clinically applied platinum drugs; (28) has been found to inhibit the growth of Lewis lung carcinoma in C57black mice as well.…”

Section: Monofunctional Platinum Complexes and Cationic Complexes Witmentioning

confidence: 97%

“…Thus we have hypothesized, that the introduction of a substituted hydantoin moiety could accordingly favor the cellular accumulation of the resultant complexes, whose 2 + electrical charge otherwise is anticipated to hamper transport through biological membranes [18]. So far we have developed a series of diammine Pt (II) complexes with cycloalkanespiro-5`-hydantoins (26,27) and more recently a racemic compound with 5-methyl-5-phenylhydantoin (PtMPH (28)), whereby the ligand is coordinated bidentatly to the complexing metal center via both endocyclic nitrogen atoms, thus forming chelate rings [73,74]. All of the compounds are found to exhibit cytotoxic effects in a micromolar concentration range against a broad spectrum of human tumor cell lines and (28) proved to be the most active complex with regard to the IC 50 values obtained.…”

Section: Monofunctional Platinum Complexes and Cationic Complexes Witmentioning

confidence: 99%

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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: Monofunctional Platinum Complexes and Cationic Complexes Witmentioning

confidence: 97%

Section: Monofunctional Platinum Complexes and Cationic Complexes Witmentioning

confidence: 99%

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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“…To examine the cytotoxic activity of Pt(II) complex 9 , the standard WST‐1 viability assay was used . Cytotoxic effect was evaluated on human T‐lymphocytic leukemia cells MOLT‐4 and human promyelocytic leukemia HL‐60 in exponential grow phase, 24 h after incubation with the cytostatic drugs.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and cytostatic activity of Pt(II) complexes of intramolecularly coordinated phosphine and stibine ligands

Řezníček

Dostál

Růžička

et al. 2012

Applied Organom Chemis

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H 3 ]SbPh 2 }PtCl 2 (6) as the result of different ability of the starting compounds 1-3 to complex platinum centre. Compounds 1-6 were characterized by 1 H, 13 C and 31 P NMR spectroscopy and electrospray ionization mass spectrometry, and molecular structures of 3-6 were determined by X-ray diffraction analysis. The substitution reactions of complexes 4-6 were also studied. The reaction of 5 and 6 with NaI yielded complexes {[2,6-(Me 2 NCH 2 ) 2 C 6 H 3 ]PPh 2 }PtI 2 (7) and {[2,6-(Me 2 NCH 2 ) 2 C 6 H 3 ]SbPh 2 }PtI 2 (8), while the same reaction of 4 with NaI did not proceed. As the compounds 7 and 8 structurally resemble cisplatin, complex {{[2-(Me 2 NCH 2 )-6-(Me 2 NHCH 2 )C 6 H 3 ]PPh 2 }PtCl 2 } + Cl À (9) was prepared as water-soluble platinum complex. The cytotoxic effect of complex 9 was evaluated on human T-lymphocytic leukemia cells MOLT-4 (IC 50 = 27.6 AE 1.8 mmol l À1 ) and human promyelocytic leukemia HL-60 (IC 50 = 55.9 AE 4.9 mmol l À1 ).

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“…Several pharmacological studies on Pt(II) complexes of cycloalkane-spirohydantoins have revealed that they have antitumor activity comparable to the one of cisplatin, and are far less toxic than the latter, which is its main drawback [10,11]. The complexation properties of some cyclic compounds containing thioamide groups, such as 2-imidazoline-2-thione [12], thiohydantoin [13,14] pseudothiohydantoin [15], 5,5-dimethyl-2,4-dithiohydantoin and its 4-thio and 2-thio analogues [16], are also studied.…”

mentioning

confidence: 99%

Copper complexes of two cycloalkanespiro-5-dithiohydantoins: Synthesis, oxidation states and characterization

Ahmedova

Marinova

Tyuliev

et al. 2008

Inorganic Chemistry Communications

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Synthesis, physicochemical and in vitro pharmacological investigation of new platinum (II) complexes with some cycloalkanespiro-5′-hydantoins

Cited by 25 publications

References 9 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

Synthesis and cytostatic activity of Pt(II) complexes of intramolecularly coordinated phosphine and stibine ligands

Copper complexes of two cycloalkanespiro-5-dithiohydantoins: Synthesis, oxidation states and characterization

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