- Multidrug resistance (MDR) is a major problem in cancer chemotherapy. The best characterized resistance mechanism is the one mediated by the over- expression of drug efflux transporters, permeability-glycoprotein (P-gp), which pump a variety of anticancer drugs out of the cells, resulting in lowered intracellular drug accumulation. A series of flavonoid dimers are developed in this invention, which are linked together by linker groups of various lengths. These flavonoid dimers are found to be efficient P-gp modulators that increase cytotoxicity of anticancer drugs in vitro and dramatically enhance their intracellular drug accumulation. It is found that the flavonoid dimers of this invention are also useful in reducing drug resistance in treating parasitic diseases.
- Inventor: CHEN, De-heng | ZHOU, Ming-xiang
Priority Number: CN101454305B
IPC Current: C07D031130 | A61K003135 | A61K0031352 | A61K0031365 | A61P003500 | C07D031132
Assignee Applicant: Mcgill University | The Hong Kong University of Science and Technology
Title: Flavonoid dimers and methods of making and using such | Flavonoid dimer and its preparing method and using method
Usefulness: Flavonoid dimers and methods of making and using such | Flavonoid dimer and its preparing method and using method
Summary: (I) is useful for reducing P-glycoprotein based multidrug resistance or reducing resistance of a drug (such as sodium stibogluconate or pentamidine) in parasitic disease caused by Leishmania , such as L.donovani , L.amazonensis , L.tarentolae , L.tropica , L.enriettii , L.mexicana and L.major , where the drug is useful to treat cancer (claimed). (I) is useful as co-drugs for the chemotherapeutic treatment of cancer. The ability of (I) to modulate the pentamidine resistance was tested in pentamidine resistant L.enriettii cells. The result showed that 1,13-bis[4'-((5,7-dihydroxy)-4H-chromen-4-on-2-yl)phenyl]-1,4,7,10,13-pentaoxatridecane (6μM) reduced the IC 50 value of pentamidine (by 3 fold) to 39.2±2.1 μg/ml.
Novelty: New flavonoid dimer compounds are P-glycoprotein modulators useful e.g. for reducing resistance of drug e.g. pentamidine in parasitic disease caused by e.g. Leishmania donovani, Leishmania amazonensis and Leishmania tropica
- CHAN Tak Hang
CHOW Larry Ming Cheung