Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex


A New 4-phenyl-1,8-naphthyridine Derivative Affects Carcinoma Cell Proliferation by Impairing Cell Cycle Progression and Inducing Apoptosis

Author(s): Antonella Capozzi, Elisabetta Mantuano, Paola Matarrese, Giuseppe Saccomanni, Clementina Manera, Vincenzo Mattei, Lucrezia Gambardella, Walter Malorni, Maurizio Sorice and Roberta Misasi

Affiliation: Dipartimento di Medicina Sperimentale, "Sapienza" University of Rome, Viale Regina Elena 324, Rome, 00161, Italy.


In targeted cancer therapy the search for novel molecules led to the discovery of a plethora of small organic molecules inhibiting cancer cell proliferation. Among these, quinazoline and derivatives, such as quinolines and naphthyridines, have been considered as of particular interest. One of these, the naphthyridine derivative 4-phenyl-2,7-di(piperazin-1-yl)-1,8-naphthyridine, has been analyzed in detail in the present work. We found that this compound elicited a powerful anti-proliferative activity on carcinoma cells, with IC50 values comparable with paradigmatic microtubule-deranging drugs. The mechanisms underlying this effect were seemingly due to a framework of cellular alterations that include peculiar alterations of mitochondria, i.e. an increase of mitochondrial membrane potential (MMP), followed by the typical MMP loss leading to the release of apoptogenic factors, and cell death by apoptosis. Furthermore, the analysis of cell cycle revealed that a significant percentage of treated cells was in G2/M phase. This block was seemingly due to a target effect of the naphthyridine derivative on microtubular network dynamic instability, which impaired mitotic spindle formation, possibly leading to mitotic catastrophy. Since the dual effects of naphthyridine derivative on cell cycle and mitotic spindle were obtained at very low concentrations, i.e. micromolar concentrations, we hypothesize that this compound could represent a new promising tool in the control of cancer cell proliferation.

Keywords: Naphthyridine derivative, Cell cycle, Apoptosis, Propidium iodide, Annexin V, Cytotoxicity, Topoisomerase II, Hep-2 cells, Mitochondria, Mitochondrial Membrane Potential, Microtubules, Tubulin, JC-1, Bromodeoxyuridine, Cancer

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Article Details

Page: [653 - 662]
Pages: 10
DOI: 10.2174/187152012800617731
Price: $58