Structure-activity relationships in 1,4-benzodioxan-related compounds. 11. (1) reversed enantioselectivity of 1,4-dioxane derivatives in α1-adrenergic and 5-HT1A receptor binding sites recognition

  • J Med Chem. 2013 Jan 24;56(2):584-8. doi: 10.1021/jm301525w.
Alessandro Bonifazi  1 ,  Alessandro Piergentili ,  Fabio Del Bello ,  Yogita Farande ,  Mario Giannella ,  Maria Pigini ,  Consuelo Amantini ,  Massimo Nabissi ,  Valerio Farfariello ,  Giorgio Santoni ,  Elena Poggesi ,  Amedeo Leonardi ,  Sergio Menegon ,  Wilma Quaglia
Affiliations
  • 1. Medicinal Chemistry Unit, School of Pharmacy, University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
PMID: 23252794 DOI: 10.1021/jm301525w
Abstract

5-HT(1A) receptor and α(1)-adrenoreceptor (α(1)-AR) binding sites recognized by the 1,4-dioxanes 2-4 display reversed stereochemical requirements. (S)-2 proved to be a potent 5-HT(1A) receptor agonist highly selective over α(1)-AR subtypes. Chirality influenced the Anticancer activity of 3 and 4 in human Prostate Cancer cells (PC-3): (R)-4, eutomer at the α(1d)-AR subtype, was the most potent. The decreased effect of 4 and (R)-4 in α(1d)-AR silenced PC-3 cells confirmed that their Anticancer activity was α(1d)-AR-dependent.