6-alkylthio-4-[1-(2,6-difluorophenyl)alkyl]-1H-[1,3,5]triazin-2-ones (ADATs): novel regulators of cell differentiation and proliferation.
Novel triazine analogues of 5-alkyl-2-alkylthio-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydropyrimidin-4(3H)-ones (F(2)-DABOs), previously described by us as nonnucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs), were tested for their antiproliferative and cytodifferentiating activity on the A-375 human melanoma cell line. Most of the tested derivatives were effective in decreasing cell proliferation, facilitating morphological differentiation, and reprogramming gene expression. All these effects were reversible upon withdrawal of RT inhibitors. Among the compounds tested, 3 f showed the highest antiproliferative effect, whereas compound 6 c, although not affecting cell proliferation, is endowed with a strong cytodifferentiating effect, which is probably related to a marked upregulation of the e-cad gene. These results support the potential of NNRTIs as valuable antitumor agents.
Sbardella
Gianluca
G
Dipartimento di Scienze Farmaceutiche Università degli Studi di Salerno Via Ponte Don Melillo, Fisciano SA, Italy.
Bartolini
Sara
S
Castellano
Sabrina
S
Artico
Marino
M
Paesano
Nicola
N
Rotili
Dante
D
Spadafora
Corrado
C
Mai
Antonello
A
D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D014227:Triazines