Preclinical studies with new pyrrolidine platinum(II) compounds

Sampedro, F.; Haperen, V. Ruiz van; Izquierdo, M; Vicens, M; Santaló, P.; Pueyo, M; Llagostera, Montserrat; Marcuello, Eugenio; Andrés, Luis de

doi:10.1016/0223-5234(96)88260-2

Cited by 8 publications

(3 citation statements)

References 12 publications

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“…2) yielded 4a (900 mg, 72%) as a yellow solid: mp 74.5 °C; IR (CHCl3) 3250 (s.br), 1740 (s), 1680 (s), 1615 (m), 1520 (s), 1460 (m), 1280 (m), 1260 (s), 1200 (s), 1160 (s), 1125 (s) cm -1 ; 1 H NMR (300 MHz, CDCl3, TMS) δ 2.91 (dd, J ) 16.6, 3.0 Hz, 1H, 4-H R# ), 3.13 (ddd, J ) 17.6, 12.3, 5.3 Hz, 1H, 4-H β# ), 3.69 (s, 3H, OCH3), 3.69 (td, J ) 13.5, 3.3 Hz, 1H, 3-H β † ), 3.89 (s, 3H, OCH3), 4.08 (dd, J ) 14.3, 4.7 Hz, 1H, 3-H R † ), 6.21 (s, 1H, 1-H ‡ ), 6.52 (s, 1H, 5-H ‡ ), 6.66 (s, 1H, 8-H ‡ ), 7.03 (d, J ) 7.6 Hz, 1H), 7.17 (t, J ) 7.7 Hz, 1H), 7.42 (t, J ) 7.6 Hz, 1H), 7.99 (d, J ) 8.3 Hz, 1H), 10.74 (s, 1H, NHCOCF3); 13 C NMR (75.5 MHz, CDCl3) δ 28.46 (C-4), 39.59 (C-3), 52.98 (C-1), 55.92 (OCH3), 56.12 (OCH3), 110.63 (2C, C-5, C-8), 116.08 (q, 1 JCF ) 288.0 Hz, CF3), 116.34 (q, 1 JCF ) 287.6 Hz, CF3), 124.68 (C-4 R# ), 124.79 (CH), 125.03 (C-8 R# ), 126.54 (CH), 129.52 (CH), 130.74 (CH), 132.02 (C), 133.90 (C), 148.62 (C-7 † ), 148.80 (C-6 † ), 156.43 (q, 2 JCF ) 37.8 Hz, COCF3), 157.36 (q, 2 JCF ) 36. 8 Hz,COCF3); EI-MS m/z (%) ) 476 (33) [M + ], 380 (15), 379 (73), 365 (20), 364 (100), 288 (10); HR-EI-MS calcd for C22H20F6N2O5 476.1171, found 476.1182. Anal.…”

Section: Methodsmentioning

confidence: 99%

“…Apparently, polar substituents or charged compounds also diminish the biological activity . The substitution of NH 3 in cisplatinum by chelate ligands such as trans -1,2-diaminocyclohexane, 3-aminohexahydroazepines, or aminomethylpiperidines , yields bicyclic chelate platinum(II) complexes with an altered spectrum of biological activity including cases with reduced cross resistance. Thus far, only few platinum(II) complexes with amine ligands of different basicity have been reported, e.g., complexes with a mixed aromatic-aliphatic amine environment around the metal.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of 1-(2-Aminophenyl)isoquinolines and the Biological Activity of Their cis-Dichloro Platinum(II) Complexes

et al. 1999

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The broad biological effects of isoquinolines prompted us to use them as chelating, nonleaving ligands in cis-platinum(II) antitumor complexes. The synthesis of several 1-(2-aminophenyl)isoquinoline derivatives with different levels of hydrogenation and varying substitution of the phenyl ring is reported. These compounds constitute a new class of ligands for the synthesis of oligocyclic platinum(II) complexes. In vitro cytotoxicity tests indicate that the most basic amine ligands afford the most effective complexes. Two of the new complexes were more potent against L1210 murine leukemia cells than the well-established antitumor compound cisplatinum.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of 1-(2-Aminophenyl)isoquinolines and the Biological Activity of Their cis-Dichloro Platinum(II) Complexes

et al. 1999

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“…The pyrrolidine derivatives fall into an important class of organic compounds, and they have received attention of biochemists because of their biochemical activities [1][2][3]. Furthermore, a great many pyrrolidine complexes have also provoked a great interest in their diverse spectra of biological and pharmaceutical activities, such as antibacterial and antitumor activities [4][5][6][7][8]. Coordination compounds of platinum have an especially rich history due to the clinical success of cisplatin and related anticancer drugs [9,10].…”

Section: Introductionmentioning

confidence: 99%

Mechanistic and Conformational Studies on the Interaction of a Platinum(II) Complex Containing an Antiepileptic Drug, Levetiracetam, With Bovine Serum Albumin by Optical Spectroscopic Techniques in Aqueous Solution

Shahabadi

Hadidi

2014

Appl Biochem Biotechnol

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Fluorescence spectroscopy in combination with circular dichroism (CD) and ultraviolet-visible (UV-vis) absorption spectroscopy were employed to investigate the binding of a new platinum(II) complex containing an antiepileptic drug "Levetiracetam" to bovine serum albumin (BSA) under the physiological conditions. In the mechanism discussion, it was proved that the fluorescence quenching of BSA by Pt(II) complex is a result of the formation of Pt(II) complex-BSA complex. The thermodynamic parameters ΔG, ΔH, and ΔS at different temperatures (283, 298, and 310 K) were calculated, and the negative value for ΔH and ΔS indicate that the hydrogen bonds and van der Waals interactions play major roles in Pt(II) complex-BSA association. Binding studies concerning the number of binding sites (n~1) and apparent binding constant K b were performed by fluorescence quenching method. The site marker competitive experiments indicated that the binding of Pt(II) complex to BSA primarily took place in site II. Based on the Förster's theory, the average binding distance between Pt(II) complex and BSA was obtained (r = 5.29 nm). Furthermore, UV-vis, CD, and synchronous fluorescence spectrum were used to investigate the structural change of BSA molecules with addition of Pt(II) complex. These results indicate that the binding of Pt(II) complex to BSA causes apparent change in the secondary structure of BSA and do affect the microenvironment around the tryptophan residue.

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Synthesis, Characterization, and DNA Binding Studies of a New Pt(II) Complex Containing the Drug Levetiracetam: Combining Experimental and Computational Methods

Shahabadi

Hadidi

Taherpour

2014

Appl Biochem Biotechnol

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The water-soluble platinum(II) complex, [Pt(LV)(dmso)Cl]Cl (LV is Levetiracetam an anti-epileptic drug belonging to the pyrrolidine family) was synthesized and characterized using physico-chemical, spectroscopic and computational methods. Multi-spectroscopic methods used to study the interaction of Pt(II) complex with calf thymus (ct-DNA) in Tris-HCl buffer solution (pH 7.4). The Pt(II) complex was found to be a minor groove binder with a preference for the A-T region compared to the G-C region. This was substantiated by displacement studies with Hoechst 33258, a known minor groove binder. The mean binding constant obtained from the spectroscopic techniques was 7 × 10(4) M(-1). In comparison with the previous study, the binding constant of Pt(II) complex is 15 times greater than the corresponding value of levetiracetam. These results indicate that the binding affinity of Pt(II) complex is stronger than levetiracetam.

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Preclinical studies with new pyrrolidine platinum(II) compounds

Cited by 8 publications

References 12 publications

Synthesis of 1-(2-Aminophenyl)isoquinolines and the Biological Activity of Their cis-Dichloro Platinum(II) Complexes

Synthesis of 1-(2-Aminophenyl)isoquinolines and the Biological Activity of Their cis-Dichloro Platinum(II) Complexes

Mechanistic and Conformational Studies on the Interaction of a Platinum(II) Complex Containing an Antiepileptic Drug, Levetiracetam, With Bovine Serum Albumin by Optical Spectroscopic Techniques in Aqueous Solution

Synthesis, Characterization, and DNA Binding Studies of a New Pt(II) Complex Containing the Drug Levetiracetam: Combining Experimental and Computational Methods

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