Silver Complexes of Miconazole and Metronidazole: Potential Candidates for Melanoma Treatment

Author:

Fabijańska Małgorzata1ORCID,Rybarczyk-Pirek Agnieszka J.2,Dominikowska Justyna2ORCID,Stryjska Karolina1ORCID,Żyro Dominik1ORCID,Markowicz-Piasecka Magdalena3ORCID,Szynkowska-Jóźwik Małgorzata Iwona4ORCID,Ochocki Justyn5ORCID,Sikora Joanna1ORCID

Affiliation:

1. Department of Bioinorganic Chemistry, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland

2. Theoretical and Structural Chemistry Group, Department of Physical Chemistry, Faculty of Chemistry, University of Lodz, Pomorska 163/165, 90-236 Lodz, Poland

3. Department of Applied Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland

4. Faculty of Chemistry, Institute of General and Ecological Chemistry, Lodz University of Technology, Zeromskiego 116, 90-543 Lodz, Poland

5. Faculty of Pharmacy, Chair of Medicinal Chemistry, Group of Bioinorganic Chemistry Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland

Abstract

Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)2AgNO3], [(MTZ)2Ag]2SO4, [Ag(MCZ)2NO3], [Ag(MCZ)2BF4], [Ag(MCZ)2SbF6] and [Ag(MCZ)2ClO4] (MTZ—metronidazole; MCZ—miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC50 values against the A375 line were demonstrated by [Ag(MCZ)2NO3] and [(MTZ)2AgNO3]. The compound [(MTZ)2AgNO3] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.

Funder

National Science Center, Poland

Medical University of Lodz grant

Wroclaw Center for Networking and Supercomputing

Polish high-performance computing infrastructure PLGrid

Publisher

MDPI AG

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