9-aminonoscapine and its use in treating cancers, including drug-resistant cancers
9-aminonoscapine, prodrugs thereof, and pharmaceutically acceptable salts thereof, are disclosed. Pharmaceutical compositions including 9-aminonoscapine, and methods of preparation and use thereof are disclosed. 9-aminonoscapine is a noscapine analog that can be used to treat and/or prevent a wide variety of cancers, including drug resistant cancers, by binding tubulin and inducing apoptosis selectively in tumor cells (ovarian and T-cell lymphoma) resistant to paclitaxel, vinblastine and teniposide. 9-aminonoscapine can perturb the progression of cell cycle by mitotic arrest, followed by apoptotic cell death associated with increased caspase-3 activation and appearance of TUNEL-positive cells. Thus, 9-aminonoscapine is a novel therapeutic agents for a variety of cancers, including ovarian and T-cell lymphoma cancers, even those that have become drug-resistant to currently available chemotherapeutic drugs.
1. A method of treating cancer in a patient, comprising administering an effective amount of a compound
having one of the following formulas:
and pharmaceutically acceptable salts thereof to a patient in need of treatment thereof.
2. The method of claim 1 , wherein the cancer is selected from the group consisting of drug-resistant ovarian cancer, drug resistant T-cell lymphoma, leukemia, non-small cell lung, colon, central nervous system (CNS), melanoma, renal, ovarian, breast and prostate cancer.
3. The method of claim 2 , wherein the cancer is drug-resistant ovarian cancer or T-cell lymphoma.
4. The method of claim 1 , wherein the cancer is a drug-resistant cancer.