6-[1-(2,6-difluorophenyl)ethyl]pyrimidinones antagonize cell proliferation and induce cell differentiation by inhibiting (a nontelomeric) endogenous reverse transcriptase.
Two 2,6-difluoro-DABO derivatives (MC 1047, 1, and MC 1220, 2, respectively) were tested against endogenous, nontelomeric reverse transcriptase (endo-RT) in human differentiating cell systems to investigate their antiproliferative and cytodifferentiating activity. The two compounds significantly reduced cell proliferation and facilitated the morphological differentiation of cells. These results propose F(2)-DABOs as useful tools in preventive and/or curative therapy to counteract the loss of differentiation in dedifferentiating pathologies and as antiproliferative drugs in tumor therapy.
Bartolini
Sara
S
Istituto Superiore di Sanità, Viale Regina Elena 299, Via del Castro Laurenziano 25, 00161 Rome, Italy.
Mai
Antonello
A
Artico
Marino
M
Paesano
Nicola
N
Rotili
Dante
D
Spadafora
Corrado
C
Sbardella
Gianluca
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005464:Fluorobenzenes; D006801:Humans; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
C425326:2-cyclopentylthio-6-(1-(2,6-difluorophenyl)ethyl)-3,4-dihydro-5-methylpyrimidin-4(3H)-one; C506288:6-(1-(2,6-difluorophenyl)ethyl)-2-(dimethylamino)-5-methylpyrimidin-4(3H)-one; D000970:Antineoplastic Agents; D005464:Fluorobenzenes; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D012194:RNA-Directed DNA Polymerase