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Synthesis, Cytotoxic Evaluation and In Silico Pharmacokinetic Prediction of Some Benzo[a]Phenazine-5-sulfonic acid Derivatives

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Cancer is one of the life threatening diseases and the development of novel anticancer molecules is limited by many reasons. In the present investigation, some novel benzo[a]phenazine-5-sulfonic acid derivatives as DNA intercalator was designed with optimized pharmacokinetic features for cancer treatment. The compounds with desired pharmcokinetic profile were synthesized and structurally characterized. Cytotoxic activity study against HL-60 tumor cell lines shows that 10-dimethyl carboxamido derivative of benzo[a]phenazine-5-sulfonic acid is found to be the most active in the series with cytotoxic activity (IC50 = 19 μM) comparable to cisplatin (IC50 = 7 μM). The study concluded that the novel benzo[a]phenazine-5-sulfonic acid derivatives were found to have enhanced DNA binding affinity and exhibited significant activity in vitro against HL-60 cell lines. This work will also guide for further development of effective DNA intercalators for cancer treatment.

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Keywords: Benzo[a]phenazine-5-sulfonic acid; cytotoxic activity; human leukemia; in silico pharmacokinetic

Document Type: Research Article

Publication date: November 1, 2009

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