PMID- 27647371
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20171207
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 24
IP  - 22
DP  - 2016 Nov 15
TI  - ArgTX-636, a polyamine isolated from spider venom: A novel class of melanogenesis 
      inhibitors.
PG  - 5685-5692
LID - S0968-0896(16)30630-7 [pii]
LID - 10.1016/j.bmc.2016.08.023 [doi]
AB  - To discover new molecules with an inhibitory activity of melanogenesis a hundred 
      of scorpions, snakes, spiders and amphibians venoms were screened for their 
      capacity to inhibit mushroom tyrosinase using 3,4-l-dihydroxyphenylalanine 
      (l-DOPA) as substrate. The Argiope lobata spider venom proved to be the most 
      active. HPLC fraction containing Argiotoxine-636 (ArgTX-636), a polyamine known 
      for its numerous biological activities, was found to also show a good regulation 
      activity of melanogenesis by inhibiting DOPA and 5,6-dihydroxyindole-2-carboxylic 
      acid (DHICA) oxidases activities, wore by tyrosinase (TYR) and tyrosinase-related 
      protein 1 (TRP-1), respectively. Our results demonstrate that ArgTX-636 reduced 
      the mushroom tyrosinase activity in a dose-dependent way with a maximal half 
      inhibitory concentration (IC(50)) value of 8.34muM, when l-DOPA is used as 
      substrate. The Lineweaver-Burk study showed that ArgTX-636 is a mixed type 
      inhibitor of the diphenolase activity. Moreover, ArgTX-636 inhibits DHICA oxydase 
      activity of mushroom tyrosinase activity with IC(50) at 41.3muM. ArgTX-636 has no 
      cytotoxicity in B16F10 melanoma cells at concentrations up to 42.1muM. The effect 
      of ArgTX-636 on melanogenesis showed that melanin production in B16F10 melanoma 
      cell decreased by approximatively 70% compared to untreated cells. ArgTX-636 
      displayed no significant effect on the TYR expression while the protein level of 
      TRP-1 decreased in B16F10 cells. Thus, ArgTX-636 could have particular interest 
      for cosmetic and/or pharmaceutical use in order to reduce important dermatoses in 
      black and mixed skins.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Verdoni, Marion
AU  - Verdoni M
AD  - Aix Marseille Univ, CNRS, ICR UMR 7273, 13397 Marseille, Cedex 20, France; 
      Laboratoire In'Oya SAS-Pole d'Activites Yvon Morandat, 1480 Av. d'Armenie, 13120 
      Gardanne, France.
FAU - Roudaut, Hermine
AU  - Roudaut H
AD  - Laboratoire In'Oya SAS-Pole d'Activites Yvon Morandat, 1480 Av. d'Armenie, 13120 
      Gardanne, France; Aix Marseille Univ, INSERM, UMR 911, CRO2, 13385 Marseille, 
      Cedex 5, France.
FAU - De Pomyers, Harold
AU  - De Pomyers H
AD  - Laboratoire LATOXAN SAS, 845 avenue Pierre Brossolette, 26800 Portes les Valence, 
      France.
FAU - Gigmes, Didier
AU  - Gigmes D
AD  - Aix Marseille Univ, CNRS, ICR UMR 7273, 13397 Marseille, Cedex 20, France.
FAU - Bertin, Denis
AU  - Bertin D
AD  - Aix Marseille Univ, CNRS, ICR UMR 7273, 13397 Marseille, Cedex 20, France.
FAU - Luis, Jose
AU  - Luis J
AD  - Aix Marseille Univ, INSERM, UMR 911, CRO2, 13385 Marseille, Cedex 5, France.
FAU - Bengeloune, Abd Haq
AU  - Bengeloune AH
AD  - Laboratoire In'Oya SAS-Pole d'Activites Yvon Morandat, 1480 Av. d'Armenie, 13120 
      Gardanne, France.
FAU - Mabrouk, Kamel
AU  - Mabrouk K
AD  - Aix Marseille Univ, CNRS, ICR UMR 7273, 13397 Marseille, Cedex 20, France. 
      Electronic address: kamel.mabrouk@univ-amu.fr.
LA  - eng
PT  - Journal Article
DEP - 20160827
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Indoleacetic Acids)
RN  - 0 (Melanins)
RN  - 0 (Polyamines)
RN  - 0 (Spider Venoms)
RN  - 108687-79-2 (argiotoxin-636)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Indoleacetic Acids/chemistry/isolation & purification/*pharmacology
MH  - Melanins/*antagonists & inhibitors/metabolism
MH  - Mice
MH  - Molecular Structure
MH  - Polyamines/chemistry/isolation & purification/*pharmacology
MH  - Spider Venoms/*chemistry
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - ArgTX-636
OT  - Argiotoxine
OT  - DHICA oxydase activity
OT  - DOPA oxydase activity
OT  - Hyperpigmentation
OT  - Melanogenesis
OT  - Spider venoms
OT  - Tyrosinase
OT  - Tyrosinase related protein 1 (TRP-1)
EDAT- 2016/10/26 06:00
MHDA- 2017/08/15 06:00
CRDT- 2016/09/21 06:00
PHST- 2016/06/15 00:00 [received]
PHST- 2016/08/14 00:00 [revised]
PHST- 2016/08/18 00:00 [accepted]
PHST- 2016/10/26 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2016/09/21 06:00 [entrez]
AID - S0968-0896(16)30630-7 [pii]
AID - 10.1016/j.bmc.2016.08.023 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2016 Nov 15;24(22):5685-5692. doi: 10.1016/j.bmc.2016.08.023. 
      Epub 2016 Aug 27.