title: Non-specific SIRT inhibition as a mechanism for the cytotoxicity of ginkgolic acids and urushiols.
abstract: Ginkgolic acids and urushiols are natural alkylphenols known for their mutagenic, carcinogenic and genotoxic potential. However, the mechanism of toxicity of these compounds has not been thoroughly elucidated so far. Considering that the SIRT inhibitory potential of anacardic acids has been hypothesized by in silico techniques, we herein demonstrated through both in vitro and computational methods that structurally related compounds such as ginkgolic acids and urushiols are able to modulate SIRT activity. Moreover, their SIRT inhibitory profile and cytotoxicity were comparable to sirtinol, a non-specific SIRT inhibitor (SIRT1 and SIRT2), and different from EX-527, a SIRT1 specific inhibitor. This is the first report on the SIRT inhibition of ginkgolic acids and urushiols. The results reported here are in line with previously observed effects on the induction of apoptosis by this class of compounds, and the non-specific SIRT inhibition is suggested as a new mechanism for their in vitro cytotoxicity.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland. Electronic address: lucie.ryckewaert@unige.ch.
authors.forename: Lucie
authors.initials: L
authors.lastname: Ryckewaert
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland. Electronic address: lionel.sacconnay@unige.ch.
authors.forename: Lionel
authors.initials: L
authors.lastname: Sacconnay
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland. Electronic address: pierre-alain.carrupt@unige.ch.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland. Electronic address: alessandra.nurisso@unige.ch.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nurisso
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland. Electronic address: claudia.avello@unige.ch.
authors.forename: Claudia
authors.initials: C
authors.lastname: Simões-Pires
mesh_terms: D020134:Catalytic Domain / Q000187:drug effects; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D012459:Salicylates / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D002396:Catechols; D012459:Salicylates; C112485:ginkgolic acid; C003747:urushiol; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2
keywords: Cytotoxicity; Ginkgolic acid; Molecular docking; SIRT1; SIRT2; Urushiol