An efficient one-pot synthesis of benzothiazolo-4 beta-anilino-podophyllotoxin congeners: DNA topoisomerase-II inhibition and anticancer activity

An efficient one-pot iodination methodology for the synthesis of benzothiazolo-4 beta-anilino-podophyllotoxin (5a-h) and benzothiazolo-4 beta-anilino-4-O-demethylepipodophyllotoxin (6a-h) congeners has been successfully developed by using zirconium tetrachloride/sodium iodide. Interestingly, this protocol demonstrates enhancement of stereoselectivity apart from the improvement in the yields in comparison to previous methods reported for such related podophyllotoxin derivatives. These compounds have been designed and synthesized using association strategy by coupling of 4 beta-podophyllotoxin and 4 beta-demethylepipodophyllotoxin with a variety of substituted aminoaryl benzothiazoles. Some of the representative compounds have been evaluated for their cytotoxicity against selected human cancer cell lines and DNA topoisomerase-II inhibition activity. (C) 2010 Elsevier Ltd. All rights reserved.