Antitumor activity of 4,5,6,7-tetrathiocino (1,2-b: 3,4-b') diimidazolyl-1,3,8,10-tetrasubstituted-2,9-dithiones (R4-todit).
A series of derivatives belonging to a new class of compounds (R4-todit) were highly cytotoxic to a panel of leukaemia- and solid tumour-derived cell lines (IC50 = 0.06-20 microM). The most potent compound was the butyl4 derivative (IC50 = 0.06-5.1 microM); T leukaemia and melanoma cells were the most susceptible cells to this inhibitor (IC50 0.06 microM and 0.1 microM, respectively). The effect of butyl4-todit was irreversible, and led to progressive cell death. The compound showed a comparable potency against exponentially growing and stationary phase cells, and against cell lines expressing the MDR phenotype. The cytotoxicity of butyl4-todit in human normal PBL was up to 20 fold lower than that shown against T leukaemia cells. When tested for antiangiogenic activity in vivo, 1.5 mg/Kg butyl4-todit resulted in over 70% inhibition of the angiogenesis process induced in mice by Kaposi's sarcoma cell secreted products.
Pani
A
A
Dipartimento di Biologia Sperimentale, Università degli Studi di Cagliari, Italy. pania@unica.it
Pinna
E
E
Scintu
F
F
Perra
G
G
Corrias
S
S
Trogu
E
E
Deplano
P
P
Colla
P L
PL
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D004317:Doxorubicin / Q000633:toxicity; D018432:Drug Resistance, Multiple; D006367:HeLa Cells; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000633:toxicity*; D007624:KB Cells; D015458:Leukemia, T-Cell; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D008545:Melanoma; D051379:Mice; D008815:Mice, Inbred Strains; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012514:Sarcoma, Kaposi / Q000098:blood supply; D013329:Structure-Activity Relationship; D013871:Thiones / Q000737:chemistry / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003470:Culture Media; D006575:Heterocyclic Compounds, 3-Ring; D007093:Imidazoles; D013871:Thiones; D004317:Doxorubicin