Novel 2,3-disubstituted 1,4-naphthoquinone derivatives and their metal complexes e Synthesis and in vitro cytotoxic effect against mouse fibrosarcoma L929 cells Violeta-Carolina Niculescu a, * , Nicolae Muresan b , Aurora Salageanu c , Catalin Tucureanu c , Gabriela Marinescu d , Liviu Chirigiu e , Costinel Lepadatu d a National Research and Development Institute for Cryogenics and Isotopes Technologies e ICIT, 4th Uzinei Street, 240050 Ramnicu Valcea, Romania b Faculty of Chemistry, University of Craiova,165 Calea Bucuresti, 200144 Craiova, Romania c National Research and Development Institute for Microbiology and Immunology, 103 Spl. Independentei, 050096 Bucharest, Romania d Institute of Physical Chemistry, 202 Spl. Independentei, 060021 Bucharest, Romania e Faculty of Pharmacy, University of Medicine and Pharmacy, 2-4 Petru Rares Street, 200349 Craiova, Romania article info Article history: Received 3 June 2011 Received in revised form 11 August 2011 Accepted 19 October 2011 Keywords: Cytotoxic Complex Fibroblast In vitro Naphthoquinone abstract Quinones have various pharmacological properties including antibacterial, antifungal, antiviral, anti- inflammatory, antipyretic and anticancer activity. Two novel 2,3-disubstituted 1,4-naphthoquinones and their metal complexes were synthesised, characterized and tested. The cytotoxic potential of the novel 2,3-disubstituted 1,4-naphthoquinones and their metal complexes was studied against L929 murine fibroblasts cells grown in vitro. The treatment resulted in a concentration-dependent cytotoxicity as indicated by MTT assay. Ó 2011 Elsevier B.V. All rights reserved. 1. Introduction Research in the field of cancer therapy has led to the develop- ment of many modern medicines and therapeutics with promising anticancer activity. Among the many natural and synthetic compounds explored for anticancer potential, compounds with quinone containing moieties form a major part. Quinones are widely distributed compounds in nature and they are reported to exhibit diverse pharmacological properties including anticancer activity [1,2]. One of the mechanisms by which quinones could induce cytotoxicity was induction of oxidative stress [3]. According to this proposed mechanism, quinones are first reduced to hydroquinones or semiquinone radicals by cellular reductases at the expense of NADPH. Then, both hydroquinones and semiquinone radicals undergo rapid autoxidation with the regeneration of the parent quinones and the concomitant formation of superoxide [3]. These quinones with the ability to induce oxidative stress are responsible for initiation of tissue damage selectively in tumour cells and this seems to be a promising approach for targeting cancer cells [4]. 1,4-naphthoquinone pharmacophore is known to impart pronounced biological effects in 1,4-naphthoquinone derivatives, leading to antitumour [5,6], antiproliferative [7], antimycobacterial [8], antiplatelet, anti-inflammatory, antiallergic [9], antimalarial [10] and antileishmanial activities [11]. The incorporation of sulphur atom in 1,4-naphthoquinone derivatives has led to anti- fungal, antibacterial, antiviral, and anticancer activities [12e16]. It has been reported that menadione (an analogue of 1,4- naphthoquinone) could induce reactive oxygen species (ROS), which mediate DNA damage in many human cultured cells, sug- gesting that this activity might be important for its therapeutic effects of naphthoquinone derivatives [17,18]. The literature offers data related to the complex compounds formed by transition metals and ligands having conjugated double bonds [19e21]. The special interest about these complexes is due, among others, to the fact that the complex compounds readily participate in reversible electron-transfer reactions. Literature mentions the important biologic-active, antimalaric, antiviral and antitumoural properties of this type of ligands; the same properties are shown by the complexes that these ligands form with metal ions, which act in the biological structures as essential microelements [19e21]. The importance of these compounds can be exemplified by * Corresponding author. Tel.: þ40 25 073 2744; fax: þ40 25 073 2746. E-mail addresses: violeta@icsi.ro, caroletyy@yahoo.com (V.-C. Niculescu). Contents lists available at SciVerse ScienceDirect Journal of Organometallic Chemistry journal homepage: www.elsevier.com/locate/jorganchem 0022-328X/$ e see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jorganchem.2011.10.036 Journal of Organometallic Chemistry 700 (2012) 13e19