New resveratrol (RES) analogs were developed by replacing the aromatic 'core' of our initial naphthalene-based RES analogs with pseudo-heterocyclic (salicylaldoxime) or heterocyclic (benzofuran, quinoline, and benzothiazole) scaffolds. The resulting analogs were tested for their antiproliferative and vasorelaxing effect, two typical properties shown by RES. Some of the new compounds confirmed strong antiproliferative activities, comparable to that previously found with the most active naphthalene-based analog. In particular, 3-(3,5-dihydroxyphenyl)-7-hydroxyquinoline exhibited the most potent antiproliferative effect (IC50=17.4 microM). In vascular assays, the highest levels of potency (pIC50=4.92) and efficacy (Emax=88.2%) were obtained with 2-(3,5-dihydroxyphenyl)-6-hydroxybenzothiazole. A conformational analysis of these compounds indicated that the antiproliferative activity on MDA-MB-231 cancer cells can be correlated to a common sterical profile of the most active compounds and, in particular, to the spatial arrangement of the three phenolic groups. Furthermore, the vasorelaxing properties showed a good correlation with the electronic properties measured through the electrostatic molecular potential (ESP).

Synthesis of heterocycle-based analogs of resveratrol and their antitumor and vasorelaxing properties

BERTINI, SIMONE;CALDERONE, VINCENZO;MARTELLI, ALMA;MARTINELLI, ADRIANO;MINUTOLO, FILIPPO;TESTAI, LARA;TUCCINARDI, TIZIANO;MACCHIA, MARCO
2010

Abstract

New resveratrol (RES) analogs were developed by replacing the aromatic 'core' of our initial naphthalene-based RES analogs with pseudo-heterocyclic (salicylaldoxime) or heterocyclic (benzofuran, quinoline, and benzothiazole) scaffolds. The resulting analogs were tested for their antiproliferative and vasorelaxing effect, two typical properties shown by RES. Some of the new compounds confirmed strong antiproliferative activities, comparable to that previously found with the most active naphthalene-based analog. In particular, 3-(3,5-dihydroxyphenyl)-7-hydroxyquinoline exhibited the most potent antiproliferative effect (IC50=17.4 microM). In vascular assays, the highest levels of potency (pIC50=4.92) and efficacy (Emax=88.2%) were obtained with 2-(3,5-dihydroxyphenyl)-6-hydroxybenzothiazole. A conformational analysis of these compounds indicated that the antiproliferative activity on MDA-MB-231 cancer cells can be correlated to a common sterical profile of the most active compounds and, in particular, to the spatial arrangement of the three phenolic groups. Furthermore, the vasorelaxing properties showed a good correlation with the electronic properties measured through the electrostatic molecular potential (ESP).
Bertini, Simone; Calderone, Vincenzo; Carboni, I; Maffei, R; Martelli, Alma; Martinelli, Adriano; Minutolo, Filippo; Rajabi, M; Testai, Lara; Tuccinardi, Tiziano; Ghidoni, R; Macchia, Marco
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/191141
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 28
  • ???jsp.display-item.citation.isi??? 28
social impact