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6‐Alkylthio‐4‐[1‐(2,6‐difluorophenyl)alkyl]‐1 H ‐[1,3,5]triazin‐2‐ones (ADATs): Novel Regulators of Cell Differentiation and Proliferation
Author(s) -
Sbardella Gianluca,
Bartolini Sara,
Castellano Sabrina,
Artico Marino,
Paesano Nicola,
Rotili Dante,
Spadafora Corrado,
Mai Antonello
Publication year - 2006
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200600139
Subject(s) - cell growth , downregulation and upregulation , cell culture , triazine , chemistry , reprogramming , alkyl , gene , gene expression , stereochemistry , biology , biochemistry , genetics , organic chemistry , polymer chemistry
Novel triazine analogues of 5‐alkyl‐2‐alkylthio‐6‐[1‐(2,6‐difluorophenyl)alkyl]‐3,4‐dihydropyrimidin‐4(3 H )‐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.