Noscapine analogs that incorporate 9-aminonoscapine for use as a cancer treatment.
- Has higher tubulin activity than noscapine.
- Induces apoptosis selectively in ovarian and T-cell lymphoma tumor cells that are already drug-resistant.
Ovarian cancer affects approximately 13 of every 100,000 women and about 80 percent of patients with ovarian cancer will have a recurrence. The different types of T-cell lymphoma are considered rare diseases. A significant number of these patients do not respond to treatment, relapse after treatment, or become resistant to specific drugs. There are a number of tubulin-binding compounds in development as therapeutics to treat these and other cancers. Tubulin-binding drugs currently on the market include vincas and taxanes. The taxanes, paclitaxel, docetaxel and Abraxane are often used to treat ovarian cancer but treatment frequently results in toxic side effects including peripheral neuropathy and neutropenia. Development of more efficient drug treatments that are effective on resistant cells will provide more options for patients with recurrent and drug-resistant cancer. Because 9-aminonoscapine reduces the dynamicity of neuronal microtubules, it is also useful for the central nervous system disorders of neurodegeneration.
Interference with microtubule/tubulin activity can lead to programmed cell death, or apoptosis, therefore microtubule-binding drugs are often used in treating cancer. However, tumor cells can develop resistances to microtubule-binding drugs currently on the market. Emory researchers have developed novel compounds that incorporate the noscapine analog, 9-aminonoscapine. This analog binds to tubulin and selectively induces apoptosis in ovarian and T-cell lymphoma tumor cells that are already resistant to paclitaxel, vinblastine, and teniposide. Specifically, 9-aminonoscapine disrupts the cell cycle via mitotic arrest which is followed by apoptotic cell death associated with increased caspase-3 activation and DNA fragmentation.
Methods for making aminonoscapine have been utilized to create a number of 9-aminonoscapine analogs.