Cytotoxic effect of (1-methyl-1H-imidazol-2-yl)-methanamine and its derivatives in PtII complexes on human carcinoma cell lines: A comparative study with cisplatin

Nicola Ferri, Stefano Cazzaniga, Luca Mazzarella, Giuseppe Curigliano, Giorgio Lucchini, Daniele Zerla, Raffaella Gandolfi, Giorgio Facchetti, Michela Pellizzoni, Isabella Rimoldi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The synthesis and pharmacological characterisation of (1-methyl-1H- imidazol-2-yl)-methanamine and its derivatives in PtII complexes are described. Six out of eleven new PtII complexes showed a significant cytotoxic effect on NCI-H460 lung cancer cell line with EC50 values between 1.1 and 0.115 mM, determined by MTT assay. Compound Pt-4a showed a particularly more potent cytotoxic effect than the previously described Pt II complex with 2,2′-bipyridine, [Pt(bpy)Cl2], with an EC50 value equal to 172.7 μM versus 726.5 μM respectively, and similar potency of cisplatin (EC50 = 78.3 μM) in NCI-H460 cell line. The determination of the intracellular and DNA-bound concentrations of 195Pt, as marker of the presence of the complexes, showed that the cytotoxic compound Pt-4a readily diffused into the cells to a similar extent of cisplatin and directly interacted with the nuclear DNA. Pt-4a induced both p53 and p21Waf expression in NCI-H460 cells similar to cisplatin. A direct comparison of the cytotoxic effect between compound Pt-4a and cisplatin on 12 different cancer cell lines demonstrated that compound Pt-4a was in general less potent than cisplatin, but it had a comparable cytotoxic effect on non-small-cell lung cancer NCI-H460 cells, and the colorectal cancer cells HCT-15 and HCT-116. Altogether, these results suggested that the PtII complex with 1-methyl-1H-imidazol-2-yl)-methanamine (compound Pt-4a), displayed a significant cytotoxic activity in cancer cells. Similarly to cisplatin this compound interacts with nuclear DNA and induces both p53 and p21waf, and thus it represents an interesting starting point for future optimisation of new PtII complexes forming DNA adducts.

Original languageEnglish
Pages (from-to)2379-2386
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number8
DOIs
Publication statusPublished - Apr 15 2013

Fingerprint

Cisplatin
Cells
Derivatives
Carcinoma
Cell Line
DNA
DNA Adducts
Non-Small Cell Lung Carcinoma
methylamine
Colorectal Neoplasms
Assays
Lung Neoplasms
Neoplasms
Pharmacology

Keywords

  • Cancer cell line
  • Cisplatin
  • Cytotoxicity
  • Imidazole
  • Platinum(II) complex

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Cytotoxic effect of (1-methyl-1H-imidazol-2-yl)-methanamine and its derivatives in PtII complexes on human carcinoma cell lines : A comparative study with cisplatin. / Ferri, Nicola; Cazzaniga, Stefano; Mazzarella, Luca; Curigliano, Giuseppe; Lucchini, Giorgio; Zerla, Daniele; Gandolfi, Raffaella; Facchetti, Giorgio; Pellizzoni, Michela; Rimoldi, Isabella.

In: Bioorganic and Medicinal Chemistry, Vol. 21, No. 8, 15.04.2013, p. 2379-2386.

Research output: Contribution to journalArticle

Ferri, Nicola ; Cazzaniga, Stefano ; Mazzarella, Luca ; Curigliano, Giuseppe ; Lucchini, Giorgio ; Zerla, Daniele ; Gandolfi, Raffaella ; Facchetti, Giorgio ; Pellizzoni, Michela ; Rimoldi, Isabella. / Cytotoxic effect of (1-methyl-1H-imidazol-2-yl)-methanamine and its derivatives in PtII complexes on human carcinoma cell lines : A comparative study with cisplatin. In: Bioorganic and Medicinal Chemistry. 2013 ; Vol. 21, No. 8. pp. 2379-2386.
@article{df9218db2a4443ee8cf9c73905b24834,
title = "Cytotoxic effect of (1-methyl-1H-imidazol-2-yl)-methanamine and its derivatives in PtII complexes on human carcinoma cell lines: A comparative study with cisplatin",
abstract = "The synthesis and pharmacological characterisation of (1-methyl-1H- imidazol-2-yl)-methanamine and its derivatives in PtII complexes are described. Six out of eleven new PtII complexes showed a significant cytotoxic effect on NCI-H460 lung cancer cell line with EC50 values between 1.1 and 0.115 mM, determined by MTT assay. Compound Pt-4a showed a particularly more potent cytotoxic effect than the previously described Pt II complex with 2,2′-bipyridine, [Pt(bpy)Cl2], with an EC50 value equal to 172.7 μM versus 726.5 μM respectively, and similar potency of cisplatin (EC50 = 78.3 μM) in NCI-H460 cell line. The determination of the intracellular and DNA-bound concentrations of 195Pt, as marker of the presence of the complexes, showed that the cytotoxic compound Pt-4a readily diffused into the cells to a similar extent of cisplatin and directly interacted with the nuclear DNA. Pt-4a induced both p53 and p21Waf expression in NCI-H460 cells similar to cisplatin. A direct comparison of the cytotoxic effect between compound Pt-4a and cisplatin on 12 different cancer cell lines demonstrated that compound Pt-4a was in general less potent than cisplatin, but it had a comparable cytotoxic effect on non-small-cell lung cancer NCI-H460 cells, and the colorectal cancer cells HCT-15 and HCT-116. Altogether, these results suggested that the PtII complex with 1-methyl-1H-imidazol-2-yl)-methanamine (compound Pt-4a), displayed a significant cytotoxic activity in cancer cells. Similarly to cisplatin this compound interacts with nuclear DNA and induces both p53 and p21waf, and thus it represents an interesting starting point for future optimisation of new PtII complexes forming DNA adducts.",
keywords = "Cancer cell line, Cisplatin, Cytotoxicity, Imidazole, Platinum(II) complex",
author = "Nicola Ferri and Stefano Cazzaniga and Luca Mazzarella and Giuseppe Curigliano and Giorgio Lucchini and Daniele Zerla and Raffaella Gandolfi and Giorgio Facchetti and Michela Pellizzoni and Isabella Rimoldi",
year = "2013",
month = "4",
day = "15",
doi = "10.1016/j.bmc.2013.01.063",
language = "English",
volume = "21",
pages = "2379--2386",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "8",

}

TY - JOUR

T1 - Cytotoxic effect of (1-methyl-1H-imidazol-2-yl)-methanamine and its derivatives in PtII complexes on human carcinoma cell lines

T2 - A comparative study with cisplatin

AU - Ferri, Nicola

AU - Cazzaniga, Stefano

AU - Mazzarella, Luca

AU - Curigliano, Giuseppe

AU - Lucchini, Giorgio

AU - Zerla, Daniele

AU - Gandolfi, Raffaella

AU - Facchetti, Giorgio

AU - Pellizzoni, Michela

AU - Rimoldi, Isabella

PY - 2013/4/15

Y1 - 2013/4/15

N2 - The synthesis and pharmacological characterisation of (1-methyl-1H- imidazol-2-yl)-methanamine and its derivatives in PtII complexes are described. Six out of eleven new PtII complexes showed a significant cytotoxic effect on NCI-H460 lung cancer cell line with EC50 values between 1.1 and 0.115 mM, determined by MTT assay. Compound Pt-4a showed a particularly more potent cytotoxic effect than the previously described Pt II complex with 2,2′-bipyridine, [Pt(bpy)Cl2], with an EC50 value equal to 172.7 μM versus 726.5 μM respectively, and similar potency of cisplatin (EC50 = 78.3 μM) in NCI-H460 cell line. The determination of the intracellular and DNA-bound concentrations of 195Pt, as marker of the presence of the complexes, showed that the cytotoxic compound Pt-4a readily diffused into the cells to a similar extent of cisplatin and directly interacted with the nuclear DNA. Pt-4a induced both p53 and p21Waf expression in NCI-H460 cells similar to cisplatin. A direct comparison of the cytotoxic effect between compound Pt-4a and cisplatin on 12 different cancer cell lines demonstrated that compound Pt-4a was in general less potent than cisplatin, but it had a comparable cytotoxic effect on non-small-cell lung cancer NCI-H460 cells, and the colorectal cancer cells HCT-15 and HCT-116. Altogether, these results suggested that the PtII complex with 1-methyl-1H-imidazol-2-yl)-methanamine (compound Pt-4a), displayed a significant cytotoxic activity in cancer cells. Similarly to cisplatin this compound interacts with nuclear DNA and induces both p53 and p21waf, and thus it represents an interesting starting point for future optimisation of new PtII complexes forming DNA adducts.

AB - The synthesis and pharmacological characterisation of (1-methyl-1H- imidazol-2-yl)-methanamine and its derivatives in PtII complexes are described. Six out of eleven new PtII complexes showed a significant cytotoxic effect on NCI-H460 lung cancer cell line with EC50 values between 1.1 and 0.115 mM, determined by MTT assay. Compound Pt-4a showed a particularly more potent cytotoxic effect than the previously described Pt II complex with 2,2′-bipyridine, [Pt(bpy)Cl2], with an EC50 value equal to 172.7 μM versus 726.5 μM respectively, and similar potency of cisplatin (EC50 = 78.3 μM) in NCI-H460 cell line. The determination of the intracellular and DNA-bound concentrations of 195Pt, as marker of the presence of the complexes, showed that the cytotoxic compound Pt-4a readily diffused into the cells to a similar extent of cisplatin and directly interacted with the nuclear DNA. Pt-4a induced both p53 and p21Waf expression in NCI-H460 cells similar to cisplatin. A direct comparison of the cytotoxic effect between compound Pt-4a and cisplatin on 12 different cancer cell lines demonstrated that compound Pt-4a was in general less potent than cisplatin, but it had a comparable cytotoxic effect on non-small-cell lung cancer NCI-H460 cells, and the colorectal cancer cells HCT-15 and HCT-116. Altogether, these results suggested that the PtII complex with 1-methyl-1H-imidazol-2-yl)-methanamine (compound Pt-4a), displayed a significant cytotoxic activity in cancer cells. Similarly to cisplatin this compound interacts with nuclear DNA and induces both p53 and p21waf, and thus it represents an interesting starting point for future optimisation of new PtII complexes forming DNA adducts.

KW - Cancer cell line

KW - Cisplatin

KW - Cytotoxicity

KW - Imidazole

KW - Platinum(II) complex

UR - http://www.scopus.com/inward/record.url?scp=84875716604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875716604&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2013.01.063

DO - 10.1016/j.bmc.2013.01.063

M3 - Article

C2 - 23462712

AN - SCOPUS:84875716604

VL - 21

SP - 2379

EP - 2386

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 8

ER -