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Isatin (1H-indole-2,3-dione) is an indole derivative and an important class of heterocyclic compounds found in many plants, such as Isatistinctoria, Calanthe discolor and Couroupitaguianensis (Da Silva, Garden & Pinto, 2001). It is also found in humans as a metabolic derivative of adrenaline (Sonawane & Tripathi, 2013).
Isatin was first obtained as a product from chromic acid oxidation of indigo dye by Erdmann and Laurent (Erdmann, 1840; Laurent, 1840) in 1841, and their synthetic derivatives are important substrates used for the synthesis of a variety of heterocyclic compounds, and used as raw materials for drug synthesis. Isatin and its derivatives are well known therapeutic agents due to their wide range of pharmacological and biological activities including anticancer (Lee, Long, Murray et al., 2001; Chapman, Magee, Stukenbrok et al., 2002), anticonvulsant (Verma, Pandeya, Singh et al., 2004), antiviral (Sriram Tanushree & Yogeeswari, 2004; Pirrung, Pansare, Sarma et al., 2005), antibacterial and antifungal (Chohan, Pervez, Rauf et al., 2004), anti-HIV and anti-inflammatory activities (Lashgari & Ziarani, 2011; Mishra & Bauerle, 2012; Walker, Kim & Nguyen, 2012). Isatinis used as a starting point in the synthesis of oligomeric or polymeric structures which are used in the field of solar energy (Zhang, Fu, Xie et al., 2011), organic memory devices creation (Xu Li, Liu et al., 2011) and organic field effect transistors (Lei, Cao, Fan et al., 2011; Ashraf, Kronemeijer, James et al., 2012).
Many methodologies have been adopted to synthesize Isatin derivatives and to explore their possible role in the treatment of various diseases. Among these protocols, the method developed by Sand-Meyer is the oldest and the most frequently used for the synthesis of Isatin (Rehn, 2004). This method involves the reaction of aniline with chloral hydrate and hydroxylamine hydrochloride in aqueous sodium sulfate to form an isonitrosoacetanilide, which after isolation, when treated with concentrated sulfuric acid produces Isatin.
Looking at the literature, it can be seen that in particular, halogenated isatin derivatives have been reported to exhibit anticancer activity. 5-Bromo-3-o-nitrophenyl isatinhydrazone and 5-bromo-(2-oxo-3-indolinyl) thiazolidine-2,4-diones substituted by various Mannich bases were found to exhibit anticancer activity against Walker carcinoma-256 and P388 lymphocytic leukemia in mice, respectively (Esheba & Salama, 1985; Popp & Pajouhesh, 1983). 6-Bromo-2- methylthio-3H-indol-3-one, tyrindoleninone, a brominated precursor to Tyrian purple, isolated from the egg masses of the Australian mollusk Dicathaisorbita has been reported as a cytotoxic marine compound (Westley, Vine, Benkendorff et al., 2006). 6-bromoisatin, a major decomposition product formed through the oxidation of tyriverdin (precursor of Tyrian purple), has been shown to have a weaker anti-cancer activity against a human lymphoma cell line in comparison with 6-Bromo-2- methylthio-3H-indol-3-one (Westley, Vine, Benkendorff et al., 2006; Benkendorff, Bremner & Davis, 2001). 5,7-Dibromoisatin,a significantly more potent as a cytotoxin than Isatin against U937 (human monocyte-like histiocytic lymphoma) cells (Vine, Locke, Ranson et al., 2007), its N-benzyl derivatives with more cytotoxicity toward these lymphoma cells and activity against a range of human cancer cell lines including a metastatic breast adenocarcinoma cell line (MDA-MB-231) (Vine, Locke, Ranson et al., 2007), and cytotoxic N-alkylhaloisatins are some examples of reported anticancer halogenated Isatins in recent researches (Vine, Locke, Ranson et al., 2007; Matesic, Locke, Bremner et al., 2008). In the recently approved drugs by FDA, a 5-fluoro-3-substituted-2-oxoindole, SU11248 (Sutent) is provided for the treatment of gastrointestinal stromal tumors and advanced renal-cell carcinoma (Prenen, Cools, Mentens et al., 2006; Motzer, Michaelson, Redman et al., 2006).