title: Synthesis of heterocycle-based analogs of resveratrol and their antitumor and vasorelaxing properties.
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).
authors: Department of Pharmaceutical Sciences, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors: Simone
authors: S
authors: Bertini
authors: Vincenzo
authors: V
authors: Calderone
authors: Isabella
authors: I
authors: Carboni
authors: Roberta
authors: R
authors: Maffei
authors: Alma
authors: A
authors: Martelli
authors: Adriano
authors: A
authors: Martinelli
authors: Filippo
authors: F
authors: Minutolo
authors: Mehdi
authors: M
authors: Rajabi
authors: Lara
authors: L
authors: Testai
authors: Tiziano
authors: T
authors: Tuccinardi
authors: Riccardo
authors: R
authors: Ghidoni
authors: Marco
authors: M
authors: Macchia
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D020650:Combinatorial Chemistry Techniques; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D013267:Stilbenes; D014665:Vasodilator Agents; D000077185:Resveratrol