title: 8-Methyl-4-(3-diethylaminopropylamino) pyrimido [4',5';4,5] thieno (2,3-b) quinoline (MDPTQ), a quinoline derivate that causes ROS-mediated apoptosis in leukemia cell lines.
abstract: The present study reports the biological activity of 8-methyl-4-(3-diethylamino-propylamino) pyrimido [4';5';4,5] thieno (2,3-b) quinoline (MDPTQ), a quinoline derivative structurally related to ellipticine and suggests a possible mechanism through which the compound induces apoptosis in carcinoma cell lines. Out of the 8 cell lines used in the study as representatives of different types of cancer, MDPTQ was found to be effective only against leukemia cell lines (HL-60 and K-562) whereas it had no effect on normal human bone marrow cells (BMC) which were used as controls. Fall mitochondrial membrane potential and increased reactive oxygen species (ROS) were mainly responsible for inducing apoptosis in the two cell lines. Cell death was demonstrated by increase in caspase 3 activity as well as phosphatidyl serine exposure. Pre-incubation with N-acetylcysteine (NAC) reduced the increased ROS and caspase 3 activity as well as phosphatidyl serine exposure. MDPTQ also caused cell cycle arrest in these cell lines. The above study for the first time reports the mode of action of a quinoline derivative, which could be a possible future candidate for leukemia therapy. However, there are lot of questions that need to be answered in terms of signalling pathways and its effects on animal models.
authors.affiliation: Reliance Life Sciences Pvt. Ltd., Dhirubhai Ambani Life Sciences Centre, Thane-Belapur Road, Navi Mumbai, 400701, India.
authors.forename: Sudheer
authors.initials: S
authors.lastname: Shenoy
authors.forename: Viraf S
authors.initials: VS
authors.lastname: Vasania
authors.forename: M
authors.initials: M
authors.lastname: Gopal
authors.forename: Ashish
authors.initials: A
authors.lastname: Mehta
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004249:DNA Damage; D004611:Ellipticines / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D010718:Phosphatidylserines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013876:Thiophenes / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
chemical_list: C522010:8-methyl-4-(3-diethylaminopropylamino)pyrimido(4',5'-4,5)thieno(2,3-b) quinoline; D017304:Annexin A5; D000970:Antineoplastic Agents; D004611:Ellipticines; D010718:Phosphatidylserines; D011804:Quinolines; D017382:Reactive Oxygen Species; D013876:Thiophenes; C034192:ellipticine; D053148:Caspase 3