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Phenanthroline Derivatives with Improved Selectivity as DNA‐Targeting Anticancer or Antimicrobial Drugs
Author(s) -
Roy Sudeshna,
Hagen Katharine D.,
Maheswari Palanisamy Uma,
Lutz Martin,
Spek Anthony L.,
Reedijk Jan,
van Wezel Gilles P.
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800097
Subject(s) - cisplatin , chemistry , antimicrobial , moiety , combinatorial chemistry , phenanthroline , phenazine , cell culture , stereochemistry , cancer cell , biochemistry , cancer , biology , organic chemistry , genetics , chemotherapy
Phenanthroline derivatives are of interest due to their potential activity against cancer, and viral, bacterial, and fungal infections. In a search for highly specific antitumor and antibacterial compounds, we report the activities of 1,10‐phenanthroline‐5,6‐dione (phendione or L 1 ), dipyrido[3,2‐ a :2′,3′‐ c ]phenazine (dppz or L 2 ), and their corresponding platinum complexes ([PtL 1 Cl 2 ] and [PtL 2 Cl 2 ]), and provide the solid‐state 3D structure for [PtL 1 Cl 2 ]. It is generally known that a toxic metal ion coordinated to an active organic moiety leads to a synergistic effect; however, we report herein that the platinum complexes [PtL 1 Cl 2 ] and [PtL 2 Cl 2 ] have weaker activities relative to those of the free ligands, especially against bacteria. Testing these agents against a variety of human cancer cell lines revealed that L 1 and [PtL 1 Cl 2 ] were at least as active as cisplatin against several of the cell lines (including a cisplatin‐resistant cell line). The absence of antibacterial activity of [PtL 1 Cl 2 ] removes the detrimental effect of phenanthrolines toward intestinal flora, suggesting a highly promising new strategy for the development of anticancer drugs with reduced side effects.