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Structure-Activity Relationships of Azaindenoisoquinolines

Detailed Technology Description
A novel process for synthesizing multiple Topoisomerase I inhibitors that have optimized structures for the greatest inhibitory activity and cytoxicity towards dividing cells was developed.
*Abstract

Topoisomerase I is an important protein found in the cell, and used to unwind and reduce torsional stress on DNA as it is being replicated. Topoisomerase I inhibitors are a useful chemotherapy agent, because cells that are constantly dividing, like cancer cells, are much more susceptible to attack; cell death will occur when topoisomerase I is inhibited. Topoisomerase I inhibitors make up a large portion of the chemotherapy market, because they can be used to target a wide variety of proliferating tumors. The characteristic of uninhibited division is a common feature in cancer that can be targeted without needing a specific marker for each cancer cell type. As more information becomes readily available, it is becoming apparent that within tumors there is a heterogeneous population of cells populating the primary tumor and the secondary tumors.

Purdue University researchers have developed a novel process for synthesizing four topoisomerase I inhibitors, and have optimized their structures for the greatest inhibitory activity and cytoxicity towards dividing cells. The compounds consist of 7-, 8-, 9-, and 10-azaindenoisoquinoline structures.

Advantages:
-Topoisomerase I is a proven target for cancer therapy
-Azaindenoisoquinolines have enhanced chemical stability and effectiveness over other Topoisomerase I inhibitors

Country/Region
USA

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