2. Academic Validation
  3. Benzothienoquinazolinones as new multi-target scaffolds: Dual inhibition of human Topoisomerase I and tubulin polymerization

Benzothienoquinazolinones as new multi-target scaffolds: Dual inhibition of human Topoisomerase I and tubulin polymerization

  • Eur J Med Chem. 2019 Nov 1:181:111583. doi: 10.1016/j.ejmech.2019.111583.
Jessica Ceramella 1,  Anna Caruso 1,  Maria Antonietta Occhiuzzi 1,  Domenico Iacopetta 2,  Alexia Barbarossa 1,  Bruno Rizzuti 3,  Patrick Dallemagne 4,  Sylvain Rault 4,  Hussein El-Kashef 5,  Carmela Saturnino 6,  Fedora Grande 1,  Maria Stefania Sinicropi 1
Affiliations

Affiliations

  • 1 Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, CS, Italy.
  • 2 Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, CS, Italy. Electronic address: domenico.iacopetta@unical.it.
  • 3 CNR-NANOTEC, Licryl-UOS Cosenza and CEMIF. Cal, Dep. of Physics, University of Calabria, Via P. Bucci, 87036, Rende, CS, Italy.
  • 4 Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ, UNICAEN, CERMN, 14000, Caen, France.
  • 5 Chemistry Department, Faculty of Science, Assiut University, 71516, Assiut, Egypt.
  • 6 Department of Science, University of Basilicata, Potenza, Italy.
PMID: 31400710 DOI: 10.1016/j.ejmech.2019.111583
Abstract

3-(Alkyl(dialkyl)amino)benzothieno[2,3-f]quinazolin-1(2H)-ones (4-9) have been designed using Ellipticine structure as a model, replacing the carbazole core and the pyridine ring with a dibenzothiophene and a pyrimidine moiety, respectively. New benzothienoquinazolinones (4-9) have been synthesized by a simple one-pot reaction employing 3-aminodibenzothiophene as starting material. The benzothienoquinazolinones obtained (4-9), were evaluated for their Anticancer activity against two breast Cancer cell lines, MDA-MB-231 and MCF-7. The results revealed that compounds 4 and 7 presented a good antitumor activity toward the triple negative MDA-MB-231, without cytotoxicity against non-tumoral cells. Furthermore, the compounds 4 and 7 can be considered important molecular multi-target tools for their dual inhibition of different cellular proteins, i.e. Tubulin and human Topoisomerase I, involved in relevant cellular processes, as predicted by in silico studies and demonstrated by in vitro assays (for compound 4).

Keywords

Benzothienoquinazolinones; Breast cancer; Cytoskeleton; Docking study; Tubulin.

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