From well-known antioxidants agents, we developed a first pharmacophore model containing four common chemical features: one aromatic ring and three hydrogen bond acceptors. This model served as a template in virtual screening of Maybridge and NCI databases that resulted in selection of sixteen compounds. The selected compounds showed a good antioxidant activity measured by three chemical tests: DPPH radical, radical, and superoxide radical scavenging. New synthetic compounds with a good correlation with the model were prepared, and some of them presented a good antioxidant activity. 1. Introduction Free radicals play an important role in the pathogenesis of many diseases, accounting for continuing interest in the identification and development of novel antioxidants that prevent radical-induced damage. In humans, several pathologies involve the overproduction of reactive oxygen species (ROS): these oxygen species such as the superoxide radical anion ( ) and hydrogen peroxide (H2O2) are formed by the partial reduction of molecular oxygen. Formation of the hydroxyl radical ( ), another ROS, is thought to occur through the one-electron reduction of H2O2. This reaction is facilitated by transition metals that are in a reduced valence state (e.g., reduced copper or iron) [1]. Additionally, there are a large number of other reactive species that are formed from the reaction ROS with biological molecules (e.g., polyunsaturated lipids, thiols, and nitric oxide (NO)) [2]. For example, reacts with NO to form peroxynitrite anion (ONOO？), which is unstable at physiological pH and rapidly decomposes. It forms potent nitrating and oxidizing species [3, 4] or hypochlorite (XOCl) that is a powerful oxidant produced by activated neutrophils via the reaction of H2O2 and Cl？, catalysed by the heme enzyme myeloperoxidase [5]. A lot of natural and synthetic products like quercetin 1, curcumine 2, resveratrol 3, Trolox 4, and N-acetylcystein 5 are known for their antioxidant activity [6–10]. Some heterocyclic compounds, either natural (phytoestrogens) or obtained by synthesis, having coumarin or quinoline rings, were studied for their biological activity. They are used especially as radicals scavenger like quercetol and coumestrol [11, 12] or the copper or iron chelating molecules such as clioquinol [13, 14]. After first studies realized in our laboratory [15–17] on new compounds with quinoline and coumarin structures and with the aim of discovering a very strong antioxidant, we decided to introduce in our research the three-dimentional generation and database searching. The
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