2. Academic Validation
  3. Design, synthesis and biological evaluation of multitarget hybrid molecules containing NHC-Au(I) complexes and carbazole moieties

Design, synthesis and biological evaluation of multitarget hybrid molecules containing NHC-Au(I) complexes and carbazole moieties

  • Eur J Med Chem. 2024 Aug 9:277:116757. doi: 10.1016/j.ejmech.2024.116757.
A D'Amato 1,  D Iacopetta 2,  J Ceramella 2,  R Troiano 1,  A Mariconda 3,  A Catalano 4,  M Marra 2,  C Saturnino 5,  C Rosano 6,  M S Sinicropi 2,  P Longo 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via Giovanni Paolo II 132, I-84084, Fisciano, SA, Italy.
  • 2 Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, I-87036, Arcavacata di Rende, CS, Italy.
  • 3 Department of Science, University of Basilicata, Via dell'Ateneo Lucano 10, I-85100, Potenza, Italy. Electronic address: annaluisa.mariconda@unibas.it.
  • 4 Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Via Orabona 4, 70126, Bari, Italy. Electronic address: alessia.catalano@uniba.it.
  • 5 Department of Science, University of Basilicata, Via dell'Ateneo Lucano 10, I-85100, Potenza, Italy.
  • 6 U.O. Proteomica e Spettrometria di Massa, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132, Genova, Italy.
PMID: 39142149 DOI: 10.1016/j.ejmech.2024.116757
Abstract

N-heterocyclic carbenes (NHCs) represent suitable ligands for rapid and efficient drug design, because they offer the advantage of being easily chemically modified and can bind several substituents, including transition metals as, for instance, gold derivatives. Gold-NHC complexes possess various biological activities and were demonstrated good candidates as Anticancer drugs. Besides, carbazole derivatives are characterized by various pharmacological properties, such as Anticancer, Antibacterial, anti-inflammatory, and anti-psychotropic. Amongst the latter, N-thioalkyl carbazoles were proved to inhibit Cancer cells damaging the nuclear DNA, through the inhibition of human topoisomerases. Herein, we report the design, synthesis and biological evaluation of nine new hybrid molecules in which NHC-Au(I) complexes and N-alkylthiolated carbazoles are linked together, in order to obtain novel biological multitarget agents. We demonstrated that the lead hybrid complexes possess Anticancer, anti-inflammatory and antioxidant properties, with a high potential as useful tools for treating distinct aspects of several diseases, amongst them Cancer.

Keywords

Anti-inflammatory; Anticancer; Antioxidant; Hybrid molecules; N-alkylthiolated carbazoles; N-heterocyclic carbenes.

Figures
Products