Resveratrol-salicylate derivatives as selective DNMT3 inhibitors and anticancer agents


Por: Aldawsari, Fahad S., Aguayo-Ortiz, Rodrigo, Kapilashrami, Kanishk, Yoo, Jakyung, Luo, Minkui, Medina-Franco, Jose L., Velazquez-Martinez, Carlos A.

Publicada: 1 ene 2016
Resumen:
Resveratrol is a natural polyphenol with plethora of biological activities. Resveratrol has previously shown to decrease DNA-methyltransferase (DNMT) enzymes expression and to reactivate silenced tumor suppressor genes. Currently, it seems that no resveratrol analogs have been developed as DNMT inhibitors. Recently, we reported the synthesis of resveratrol-salicylate derivatives and by examining the chemical structure of these analogs, we proposed that these compounds could exhibit DNMT inhibition especially that they resembled NSC 14778, a compound we previously identified as a DNMT inhibitor by virtual screening. Indeed, using in vitro DNMT inhibition assay, some of the resveratrol-salicylate analogs we screened in this work that showed selective inhibition against DNMT3 enzymes which were greater than resveratrol. A molecular docking study revealed key binding interactions with DNMT3A and DNMT3B enzymes. In addition, the most active analog, 10 showed considerable cytotoxicity against three human cancer cells; HT-29, HepG2 and SK-BR-3, which was greater than resveratrol. Further studies are needed to understand the anticancer mechanisms of these derivatives. © 2015 Informa UK Ltd.

Filiaciones:
Aldawsari, Fahad S.:
 Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB, Canada

Aguayo-Ortiz, Rodrigo:
 Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City, DF, Mexico

Kapilashrami, Kanishk:
 Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, 1275 York Ave, New York, NY 10021 USA

Yoo, Jakyung:
 Daewoong Pharmaceut Co Ltd, Life Sci Res Inst, Pogok Eup, South Korea

Luo, Minkui:
 Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, 1275 York Ave, New York, NY 10021 USA

Medina-Franco, Jose L.:
 Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City, DF, Mexico

Velazquez-Martinez, Carlos A.:
 Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB, Canada
ISSN: 14756366
Editorial
Taylor and Francis Ltd, 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 31 Número: 5
Páginas: 695-703
WOS Id: 000379783700002
ID de PubMed: 26118420

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