A novel structural derivative of natural alkaloid ellipticine, MDPSQ, induces necrosis in leukemic cells.
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.
Shahabuddin
M S
MS
Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India.
Nambiar
Mridula
M
Moorthy
Balaji T
BT
Naik
Prakruthi L
PL
Choudhary
Bibha
B
Advirao
Gopal M
GM
Raghavan
Sathees C
SC
D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D004611:Ellipticines / Q000737:chemistry* / Q000494:pharmacology*; D042822:Genomic Instability / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D009336:Necrosis / Q000139:chemically induced* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D011419:Propidium / Q000378:metabolism
C561025:8-methyl-4-(3-diethylaminopropylamino)pyrimido((4',5':4,5)selenolo(2,3-b)quinoline); D000470:Alkaloids; D017304:Annexin A5; D004273:DNA, Neoplasm; D004611:Ellipticines; D009363:Neoplasm Proteins; D016566:Organoselenium Compounds; D010718:Phosphatidylserines; C034192:ellipticine; D011419:Propidium