Cancer is second leading cause of death worldwide. Based on hybridization of chemotypes of some natural product-anticancer drugs/agents, indenoindolones were considered as important scaffold for potential anticancer activity.  Towards exploration of their synthesis relevant to medicinal chemistry, we have developed a ZrCl4-mediated regio- and chemoselective Friedel-Crafts acylation of indole1 and an efficient route of ZrCl4-mediated Friedel�Crafts 3-acylation of indole with 2-bromobenzoyl chlorides and the intramolecular direct arylation for synthesis of indenoindolones.2 ZrCl4-catalysis minimizes/eliminates common competing reactions that occur due to high and mutliatom-nucleophilic character of indole. These reactions are feasible for NH-unprotected indoles. Several moieties, which are commonly integrated into bio-active compounds, can be incorporated at ease by this synthesis. Indenoindolone derivatives have shown anticancer activities of higher potency and lower toxicity than clinically used drugs etoposide and 5-fluorouracil. DAPI nuclear staining and FACS analysis have indicated their apoptotic effect majorly in G1 phase of cell cycle.3 References Guchhait, S. K.; Kashyap, M.; Kamble, H. J. Org. Chem. 2011 , 76, 4753.Guchhait, S. K.; Kashyap, M. (manuscript communicated for publication in SYNTHESIS ). Kashyap, M.; Guchhait, S. K.; Kundu, C. N. (manuscript under prepration).

Novel synthesis and biological evaluation of indenoindolones as potent anticancer agents that induce major apoptosis in G1 phase

243rd National Meeting (2012)

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