The development of innovative chemotherapeutic treatments for cancer has made great strides within the last few decades. Of these, the inhibitor development for the two enzymes that play the biggest role in the uncoiling and recoiling process i.e., topoisomerase I and topoisomerase II, was base for developing novel antineoplastic drugs. To name some recognizable drugs, the topoisomerase I inhibitors are camptothecin and its derivatives. Topoisomerase II inhibitors include doxorubicin, etoposides and mitoxantrone. One of the characterized mechanisms associated with resistance against individual topo interactive agents is a decreased level or activity of the target enzyme. Since the topo-I enzyme function is essential to very basic cell survival requirements such as DNA replication, transcription, and repair processes, commonly a decreased activity of topo-I is compensated for by topo-II. A solution to the problem of multidrug resistance and effective treatment is to develop dual inhibitor of both topo-I and topo-II. The dual targeting would result in its high efficacies. We have developed novel scaffolds for dual inhibitors topo I & II by integrating the structural requirement of both the inhibitors. We mainly used make the hybrids of camptothecin, luotonin, rutaecarpine, calothrixin etc which have been proven drugs individually in the clinic with mitoxantrone. Synthesis and acitvity details will be presented.

Design and development of quinazolinone natural products based novel dual topoisomerase inhibitors

250th National Meeting (2015)

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