Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer

Author(s)

Ana Podolski-Renić, Ana Čipak Gašparović, Andreia Valente, Óscar López, Julia H. Bormio Nunes, Christian R. Kowol, Petra Heffeter, Nenad R. Filipović

Abstract

Overcoming multidrug resistance (MDR) is one of the major challenges in cancer therapy. In this respect, Schiff base-related compounds (bearing a R₁R₂C[dbnd]NR₃ bond) gained high interest during the past decades. Schiff bases are considered privileged ligands for various reasons, including the easiness of their preparation and the possibility to form complexes with almost all transition metal ions. Schiff bases and their metal complexes exhibit many types of biological activities and are used for the treatment and diagnosis of various diseases. Until now, 13 Schiff bases have been investigated in clinical trials for cancer treatment and hypoxia imaging. This review represents the first collection of Schiff bases and their complexes which demonstrated MDR-reversal activity. The areas of drug resistance covered in this article involve: 1) Modulation of ABC transporter function, 2) Targeting lysosomal ABCB1 overexpression, 3) Circumvention of ABC transporter-mediated drug efflux by alternative routes of drug uptake, 4) Selective activity against MDR cancer models (collateral sensitivity), 5) Targeting GSH-detoxifying systems, 6) Overcoming apoptosis resistance by inducing necrosis and paraptosis, 7) Reactivation of mutated p53, 8) Restoration of sensitivity to DNA-damaging anticancer therapy, and 9) Overcoming drug resistance through modulation of the immune system. Through this approach, we would like to draw attention to Schiff bases and their metal complexes representing highly interesting anticancer drug candidates with the ability to overcome MDR.

Organisation(s)

Department of Inorganic Chemistry

External organisation(s)

University of Belgrade, Rudjer Boskovic Institute, Universidade de Lisboa, Universidad de Sevilla, Medizinische Universität Wien

Journal

European Journal of Medicinal Chemistry

Volume

270

ISSN

0223-5234

DOI

https://doi.org/10.1016/j.ejmech.2024.116363

Publication date

04-2024

Peer reviewed

Yes

Austrian Fields of Science 2012

104003 Inorganic chemistry, 301305 Medical chemistry, 301904 Cancer research

Keywords

ASJC Scopus subject areas

Pharmacology, Drug Discovery, Organic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/2d79fb25-ee8b-4218-a2ae-777fb4dc1bd7