Indenoindolone derivatives as topoisomerase IIainhibiting anticancer agents

Based on known heterocyclic topoisomerase II inhibitors and anticancer agents, various indenoindolone derivatives were predicted as potential topoisomerase IIainhibiting anticancer agents. They are hydrazones, (thio)semicarbazones, and oximes of indenoindolones, and indenoindolols. These derivatives...

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Published in:Bioorganic & medicinal chemistry letters 2013-02, Vol.23 (4), p.934-938
Main Authors: Kashyap, Maneesh, Kandekar, Somnath, Baviskar, Ashish T, Das, Dipon, Preet, Ranjan, Mohapatra, Purusottam, Satapathy, Shakti Ranjan, Siddharth, Sumit, Guchhait, Sankar K, Kundu, Chanakya N, Banerjee, Uttam C
Format: Article
Language:English
Subjects:
5-Fluorouracil
Antitumor activity
Antitumor agents
DNA
DNA topoisomerase
DNA topoisomerase (ATP-hydrolysing)
Etoposide
Intercalation
oximes
Toxicity
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Summary:Based on known heterocyclic topoisomerase II inhibitors and anticancer agents, various indenoindolone derivatives were predicted as potential topoisomerase IIainhibiting anticancer agents. They are hydrazones, (thio)semicarbazones, and oximes of indenoindolones, and indenoindolols. These derivatives with suitable substitutions exhibited potent specific inhibition of human DNA TopoII[alpha] while not showing inhibition of topoisomerase I and DNA intercalation, despite the fact that parent indenoindolones are known poor/moderate inhibitors of topoisomerase II. The potent topoisomerase II inhibitor indenoindolone derivatives exhibited good anticancer activities compared to etoposide and 5-fluorouracil, and relatively low toxicity to normal cells. These derivatizations of indenoindolones were found to result in enhancement of anticancer activities.
ISSN:0960-894X