Submit Manuscript  

Article Details


Aryl Butenes Active against K562 Cells and Lacking Tyrosinase Inhibitory Activity as New Leads in the Treatment of Leukemia

[ Vol. 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   Pages 1294 - 1301 ( 8 )

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.

Keywords:

Anti-tyrosinase activity, aryl butenes, chronic myeloid leukemia, ferrociphenol, hydroxytamoxifen, imatinib, skin depigmentation.

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, Laboratoire de Biotechnologie Moleculaire des Eucaryotes, Centre de Biotechnologie de Sfax, Universite de Sfax, 3018 Sfax, Laboratoire de Biotechnologie Moleculaire des Eucaryotes, Centre de Biotechnologie de Sfax, Universite de Sfax, 3018 Sfax, Laboratoire de Biotechnologie Moleculaire des Eucaryotes, Centre de Biotechnologie de Sfax, Universite de Sfax, 3018 Sfax, Department of Pharmaceutical Chemistry, Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala 133207, Haryana, Universite Pierre et Marie Curie-Paris, Sorbonne Universites, Institut Parisien de Chimie Moleculaire (IPCM) - UMR 8232, 4 place Jussieu, 75252 Paris Cedex 05, Universite Pierre et Marie Curie-Paris, Sorbonne Universites, Institut Parisien de Chimie Moleculaire (IPCM) - UMR 8232, 4 place Jussieu, 75252 Paris Cedex 05, Laboratoire de Biotechnologie Moleculaire des Eucaryotes, Centre de Biotechnologie de Sfax, Universite de Sfax, 3018 Sfax, Universite Pierre et Marie Curie-Paris, Sorbonne Universites, Institut Parisien de Chimie Moleculaire (IPCM) - UMR 8232, 4 place Jussieu, 75252 Paris Cedex 05

Graphical Abstract:



Read Full-Text article