Xanthones as P-glycoprotein modulators and their impact on drug bioavailability

• Type: Another Publication in an International Scientific Journal
• Date: 2021

Authors

Silva, V (Author) Other; Gil Martins, E (Author) Other; Silva, B (Author) Other; Rocha Pereira, C (Author) Other; Emilia Sousa (Author) FFUP; Fernando Remiao (Author) FFUP; Silva, R (Author) Other

Journal

Title: Expert Opinion on Drug Metabolism and Toxicology

Vol. 17

Pages: 441-482

ISSN: 1742-5255

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00T-VEW

DOI: 10.1080/17425255.2021.1861247

Abstract (EN): Introduction: P-glycoprotein (P-gp) is an important efflux pump responsible for the extruding of many endogenous and exogenous substances out of the cells. P-gp can be modulated by different molecules - including xanthone derivatives - to surpass the multidrug resistance (MDR) phenomenon through P-gp inhibition, or to serve as an antidotal strategy in intoxication scenarios through P-gp induction/activation. Areas covered: This review provides a perspective on P-gp modulators, with particular focus on xanthonic derivatives, highlighting their ability to modulate P-gp expression and/or activity, and the potential impact of these effects on the pharmacokinetics, pharmacodynamics and toxicity of P-gp substrates. Expert opinion: Xanthones, of natural or synthetic origin, are able to modulate P-gp, interfering with its protein synthesis or with its mechanism of action, by decreasing or increasing its efflux capacity. These modulatory effects make the xanthonic scaffold a promising source of new derivatives with therapeutic potential. However, the mechanisms beyond the xanthones-mediated P-gp modulation and the chemical characteristics that make them more potent P-gp inhibitors or inducers/activators are still understudied. Furthermore, a new window of opportunity exists in the neuropathologies field, where xanthonic derivatives with potential to modulate P-gp should be further explored to optimize the prevention/treatment of brain pathologies.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 42