Biological Activity of NHC-Gold-Alkynyl Complexes Derived from 3-Hydroxyflavones

Inés Mármol; Javier Quero; Paula Azcárate; Elena Atrián-Blasco; Carla Ramos; Joana Santos; María Concepción Gimeno; María Jesús Rodríguez-Yoldi; Elena Cerrada

doi:10.3390/pharmaceutics14102064

Biological Activity of NHC-Gold-Alkynyl Complexes Derived from 3-Hydroxyflavones

Pharmaceutics. 2022 Sep 27;14(10):2064. doi: 10.3390/pharmaceutics14102064.

Authors

Inés Mármol^{1

2}, Javier Quero², Paula Azcárate¹, Elena Atrián-Blasco³, Carla Ramos⁴, Joana Santos⁴, María Concepción Gimeno¹, María Jesús Rodríguez-Yoldi², Elena Cerrada¹

Affiliations

¹ Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., Pedro Cerbuna 12, 50009 Zaragoza, Spain.
² Departamento de Farmacología y Fisiología, Medicina Legal y Forense, Unidad de Fisiología, Universidad de Zaragoza, CIBERobn, IIS Aragón, IA2, 50013 Zaragoza, Spain.
³ Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain.
⁴ Escola Superior de Tecnologia e Gestão, Instituto Politécnico de Viana do Castelo, Avenida do Atlântico No. 644, 4900-348 Viana do Castelo, Portugal.

Abstract

In this paper we describe the synthesis of new N-heterocyclic carbene (NHC) gold(I) derivatives with flavone-derived ligands with a propargyl ether group. The compounds were screened for their antimicrobial and anticancer activities, showing greater activity against bacteria than against colon cancer cells (Caco-2). Complexes [Au(L2b)(IMe)] (1b) and [Au(L2b)(IPr)] (2b) were found to be active against both Gram-positive and Gram-negative strains. The mechanism of action of 1b was evaluated by measurement of thioredoxin reductase (TrxR) and dihydrofolate reductase (DHFR) activity, besides scanning electron microscopy (SEM). Inhibition of the enzyme thioredoxin reductase is not observed in either Escherichia Coli or Caco-2 cells; however, DHFR activity is compromised after incubation of E. coli cells with complex 1b. Moreover, loss of structural integrity and change in bacterial shape is observed in the images obtained from scanning electron microscopy (SEM) after treatment E. coli cells with complex 1b.

Keywords: Alkynyl; N-heterocyclic carbene; antibacterial; anticancer; dihydrofolate reductase; gold complexes; hydroxyflavones; thioredoxin reductase.

Grants and funding

This research was funded by the Agencia Estatal de Investigación (projects PID2019-104379RB-C21/AEI/10.13039/501100011033, RED2018-102471-T/MCIN/AEI/10.13039/501100011033 and SAF2016-75441-R), CIBERobn under Grant (CB06/03/1012) of the Instituto Carlos III, European Grant Interreg/SUDOE (Redvalue, SOE1/PI/E0123) and Aragon Regional Government (B16-R17 and E07_20R).