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


CONCLUSIONS
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.
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.
Mehdi El
ME
Arbi
Laboratoire de Biotechnologie Moleculaire des Eucaryotes, Centre de Biotechnologie de Sfax, Universite de Sfax, 3018 Sfax, Tunisia.
Emna
E
Ketata
Laboratoire de Biotechnologie Moleculaire des Eucaryotes, Centre de Biotechnologie de Sfax, Universite de Sfax, 3018 Sfax, Tunisia.
Aref
A
Neifar
Laboratoire de Biotechnologie Moleculaire des Eucaryotes, Centre de Biotechnologie de Sfax, Universite de Sfax, 3018 Sfax, Tunisia.
Wafa
W
Mihoubi
Department of Pharmaceutical Chemistry, Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala 133207, Haryana, India.
Girish K
GK
Gupta
Universite Pierre et Marie Curie-Paris, Sorbonne Universites, Institut Parisien de Chimie Moleculaire (IPCM) - UMR 8232, 4 place Jussieu, 75252 Paris Cedex 05, France.|PSL, Chimie ParisTech, 11 rue Pierre et Marie Curie, F-75005 Paris, France.
Pascal
P
Pigeon
Universite Pierre et Marie Curie-Paris, Sorbonne Universites, Institut Parisien de Chimie Moleculaire (IPCM) - UMR 8232, 4 place Jussieu, 75252 Paris Cedex 05, France.
Siden
S
Top
Laboratoire de Biotechnologie Moleculaire des Eucaryotes, Centre de Biotechnologie de Sfax, Universite de Sfax, 3018 Sfax, Tunisia.
Ali
A
Gargouri
Universite Pierre et Marie Curie-Paris, Sorbonne Universites, Institut Parisien de Chimie Moleculaire (IPCM) - UMR 8232, 4 place Jussieu, 75252 Paris Cedex 05, France.|PSL, Chimie ParisTech, 11 rue Pierre et Marie Curie, F-75005 Paris, France.
Gerard
G
Jaouen
D000475:Alkenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D020134:Catalytic Domain; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006860:Hydrogen Bonding; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
D000475:Alkenes; D004791:Enzyme Inhibitors; D013629:Tamoxifen; C016601:afimoxifene; C558934:butylene; D014442:Monophenol Monooxygenase
Anti-tyrosinase activity; aryl butenes; chronic myeloid leukemia; ferrociphenol; hydroxytamoxifen; imatinib; skin
depigmentation.