Issue in Honor of Prof. Vincenzo Tortorella ARKIVOC 2004 (v) 85-96
Synthesis of new pyrido[4,3-g and 3,4-g]quinoline-5,10-dione and dihydrothieno[2,3-g and 3,2-g]quinoline-4,9-dione derivatives and preliminary evaluation of cytotoxic activity
Isabel Gomez-Monterrey,1 Pietro Campiglia,1 Teresa Lama,1 Paolo La Colla,2 Maria V. Diurno,1 Paolo Grieco,1 and Ettore Novellino1*
1 Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli "Federico II", Naples, Italy, 2 Dipartimento di Biologia Sperimentale, Sezione di Microbiologia, Università di Cagliari, 09124 Cagliari, Italy E-mail: novellin@unina.it
In honour of Professor Vincenzo Tortorella in the occasion of his “Fuori Ruolo” status (received 27 Oct 03; accepted 10 Feb 04; published on the web 14 Feb 04)
Abstract
Several pyrido[4,3-g and 3,4-g]quinoline-5,10-dione and dihydrothieno[2,3-g and 3,2g] quinoline-4,9-dione derivatives were synthesized and evaluated for their potential cytotoxic properties. A number of these compounds exhibited significant in vitro antiproliferative activity at submicromolar concentration in a preliminary evaluation for their cytotoxic activity using the MT-4 cell line. These structures represent potential scaffolds in discovery of new agents with antitumoral activity and the synthetic strategy developed could be used to prepare libraries of new derivatives by combinatorial chemistry.
Keywords: Cytotoxic agents, quinolinedione derivatives, MT-4 cell line
Introduction
The quinone nucleus is an important structural moiety in a number of complex chemotherapeutic agents target the DNA, playing an important role in determining their biological activities. Doxorubicin and mitoxantrone are representative of this class and are widely used in the treatment of several leukaemia and lymphomas as well as in combination chemotherapy of solid tumors.1
The importance of this class of antitumour agents has stimulated a number of studies, aimed to developing new agents that retain the core quinonic moiety yet exhibit different spectra of potency, together with reduced overall toxicity.2 In this sense, the introduction of heteroatom (N, S) into different positions of the basic quinone system, has been one of approach adopted in
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