Systematic review and QSPR analysis of chemical penetration through the nail to inform onychomycosis candidate selection.

Drug Discov Today

Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK; Centre for Pharmaceutical Medicine Research, Institute of Pharmaceutical Science, King's College, SE1 9NH, UK. Electronic address:

Published: January 2024

Recalcitrant nail plate infections can be life-long problems because localizing antifungal agents into infected tissues is problematic. In this systematic review, guided by the SPIDER method, we extracted chemical nail permeation data for 38 compounds from 16 articles, and analyzed the data using quantitative structure-property relationships (QSPRs). Our analysis demonstrated that low-molecular weight was essential for effective nail penetration, with <120 g/mol being preferred. Interestingly, chemical polarity had little effect on nail penetration; therefore, small polar molecules, which effectively penetrate the nail, but not the skin, should be set as the most desirable target chemical property in new post-screen onychomycosis candidate selections.

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http://dx.doi.org/10.1016/j.drudis.2023.103844DOI Listing

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