Title:Aryl Butenes Active against K562 Cells and Lacking Tyrosinase Inhibitory Activity as New Leads in the Treatment of Leukemia
Volume: 18
Issue: 15
Author(s): Mehdi El Arbi*, Emna Ketata, Aref Neifar, Wafa Mihoubi, Girish K. Gupta, Pascal Pigeon, Siden Top, Ali Gargouri and Gerard Jaouen
Affiliation:
- Laboratoire de Biotechnologie Microbienne et d`Ingenierie des Enzymes (LBMIE). Centre de Biotechnologie de Sfax, Université de Sfax, Route de Sidi Mansour Km 6, BP 1177, 3018 Sfax,Tunisia
Keywords:
Anti-tyrosinase activity, aryl butenes, chronic myeloid leukemia, ferrociphenol, hydroxytamoxifen, imatinib, skin
depigmentation.
Abstract: Background & Objective: The inhibitory effects of four series of aryl butene derivatives, active
against breast cancer, on the monophenolase activity of tyrosinase, in melanin-free ink from Sepia officinalis,
have been studied. Hydroxytamoxifen 1, ferrociphenol 17 and several aryl butene analogs
have shown strong antiproliferative activity on hormone-dependent and hormone-independent breast
cancer cells and were evaluated in leukemia K562 cell proliferation. Their potential to induce skin depigmentation
by evaluating their anti-tyrosinase activity was also estimated. In order to better rationalize
the tyrosinase inhibitory action and the binding mode of the compounds, docking studies were carried
out.
Conclusion: Hydroxytamoxifen and some aryl butenes showed strong antiproliferative effects against
K562 cells at 1 µM without showing tyrosinase inhibition. If phenolic compounds 16 and 17 showed
the best antiproliferative activity on K562, Hydroxytamoxifen and compounds 5, 10, 20 and 21 have
been identified as candidates for further development against chronic myeloid leukemia (CML), and
are predicted to not induce depigmentation of the skin, a side effect encountered with imatinib, conventionally
used for the treatment of CML.
