Comparison of responses of DNA topoisomerase I from Candida albicans and human cells to four new agents which stimulate topoisomerase-dependent DNA nicking

• Published in: FEMS microbiology letters Vol. 138; no. 2-3; pp. 105 - 111
• Main Authors: Fostel, J., Montgomery, D., Lartey, P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.1996; Blackwell; Oxford University Press
• Subjects: 5‐Hydroxyindoleacetic acid; Acetic acid; Anthraquinones - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - pharmacology; Antifungal therapy; Biological and medical sciences; Camptothecin; Camptothecin - pharmacology; Candida albicans; Candida albicans - enzymology; Carboxylic acids; Catecholamines - pharmacology; Chemical compounds; Deoxyribonucleic acid; Dibenzo-p-dioxin; Dioxins; Dioxins - pharmacology; DNA; DNA - metabolism; DNA Damage; DNA topoisomerase; DNA Topoisomerases, Type I - drug effects; DNA Topoisomerases, Type I - isolation & purification; DNA Topoisomerases, Type I - metabolism; Fungi; Fungi - drug effects; Fungicides; HeLa Cells; Humans; Hydroxyindoleacetic Acid - pharmacology; Indoleacetic acid; Medical sciences; Microbiology; Mode of action; Naphthalenesulfonates - pharmacology; Nicking endonuclease; Pharmacology; Pharmacology. Drug treatments; Quinizarin; Selectivity; Species Specificity; 5-Hydroxyindoleacetic acid; Antifungal therapy; DNA damage; Quinizarin; Candida albicans; Yeast; Dioxin derivatives; Enzyme; DNA topoisomerase; In vitro; Naphthalene derivatives; Fungi; Antifungal agent; Isomerases; Aromatic compound; Fungi Imperfecti; Indole derivatives; Mechanism of action; Thallophyta
• ISSN: 0378-1097; 1574-6968
• DOI: 10.1111/j.1574-6968.1996.tb08142.x

Abstract DNA topoisomerase I is a potential target for therapeutic antifungal agents predicted to have a fungicidal mode of action. This report describes four agents with varying degrees of selectivity for the fungal topoisomerase I compared to the human enzyme: 5-hydroxy-1H-indole-3-acetic acid (5-HIAA), quinizarin, dibenzo-p-dioxin-2-carboxylic acid and 7-amino-4-hydroxy-2-naphthalenesulfonic acid. Taken together with the response of topoisomerase to camptothecin and aminocatechol, these data suggest that there are sufficient structural differences between the topoisomerase I from Candida albicans and human cells to allow selective targeting of the fungal topoisomerase I over its human counterpart.