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Bioorg Med Chem. 2013 Apr 15;21(8):2379-2386. doi: 10.1016/j.bmc.2013.01.063. Epub 2013 Feb 5.

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

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Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
Division of Medical Oncology, Department of Medicine, Istituto Europeo di Oncologia, Milano, Italy.
Dipartimento di Scienze Agrarie e Ambientali-Produzione, Territorio, Agroenergia, Università degli Studi di Milano,Via Celoria 2, 20133 Milano, Italy.
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Venezia 21, 20133 Milano, Italy.
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Venezia 21, 20133 Milano, Italy. Electronic address:


The synthesis and pharmacological characterisation of (1-methyl-1H-imidazol-2-yl)-methanamine and its derivatives in Pt(II) complexes are described. Six out of eleven new Pt(II) 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 (195)Pt, 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 p21(Waf) 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 Pt(II) 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 p21(waf), and thus it represents an interesting starting point for future optimisation of new Pt(II) complexes forming DNA adducts.

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