A novel structural derivative of natural alkaloid ellipticine, MDPSQ, induces necrosis in leukemic cells

作者：Shahabuddin M S; Nambiar Mridula; Moorthy Balaji T; Naik Prakruthi L; Choudhary Bibha; Advirao Gopal M; Raghavan Sathees C^*

来源：Investigational New Drugs, 2011, 29(4): 523-533.

DOI：10.1007/s10637-009-9379-5

• Chemotherapy
• Double-strand breaks
• Cytotoxicity
• DNA damage
• Anti cancer drugs

DNA intercalating molecules are promising chemotherapeutic agents. In the present study, a novel DNA intercalating compound of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having 8-methyl-4-(3 diethylaminopropylamino) side chain is studied for its chemotherapeutic properties. Our results showed that 8-methyl-4-(3 diethylaminopropylamino) pyrimido [4',5':4,5] selenolo(2,3-b)quinoline (MDPSQ) induces cytotoxicity in a time- and concentration-dependent manner on leukemic cell lines. Both cell cycle analysis and tritiated thymidine assays revealed that MDPSQ affects DNA replication. Treatment with MDPSQ resulted in both elevated levels of DNA strand breaks and repair proteins, further indicating its cytotoxic effects. Besides, Annexin V/PI staining revealed that MDPSQ induces cell death by triggering necrosis rather than apoptosis.

• 出版日期2011-8