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6-Alkylthio-4-[1-(2,6-difluorophenyl)alkyl]-1H-[1,3,5]triazin-2-ones (ADATs): Novel Regulators of Cell Differentiation and Proliferation

✍ Scribed by Gianluca Sbardella; Sara Bartolini; Sabrina Castellano; Marino Artico; Nicola Paesano; Dante Rotili; Corrado Spadafora; Antonello Mai

Publisher: John Wiley and Sons
Year: 2006
Tongue: English
Weight: 249 KB
Volume: 1
Category: Article
ISSN: 1860-7179
DOI: 10.1002/cmdc.200600139

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✦ Synopsis

Abstract

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.

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