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Repurposing Common Food Additives (Benzo Derivatives) As New Anti-parasitic Agents
1 , 2 , 3 , 3 , 1 , 1 , * 2
1  Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA;
2  Department of Biological Sciences, University of the Pacific, 3601 Pacific Avenue, Stockton, CA95211, USA.
3  Center for Discovery and Innovation in Parasitic Diseases, University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, 9500 Gilman Drive, La Jolla, CA 92093-0756, USA;

Published: 11 November 2019 by MDPI in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

This study examined the anti-protozoal effects of selected benzo derivatives, namely ten gallic acid (GA) alkyl esters (viz., benzoic acid analogs) and twenty-three benzaldehyde analogs, against six different anaerobic human protozoal pathogens- - Trichomonas vaginalis, Tritrichomonas foetus, Tritrichomonas foetus-like, Giardia lamblia, Entamoeba histolytica, and Naegleria fowleri. The efficacy of benzaldehyde and gallate (3,4,5-trihydroxybenzoic acid) analogs were investigated in two respects: (1) changing types of side chains and their positions on the benzaldehyde ring [structure–activity relationships (SAR)]; and, (2) changing lengths of alkyl chains esterified with the carboxyl group on gallate. Results of parasite growth inhibition assays indicated that benzo derivatives could be further developed as potent anti-protozoal drug candidates/leads, where GA having longer alkyl chains exhibited higher anti-protozoal activity than compounds with shorter alkyl chains or all benzaldehyde analogs tested. The chemical libraries were also screened against common human microbiome bacteria and no detectable inhibition was observed. Structure-activity relationships and their implications for new drug discovery against these sexually-transmitted, water-borne, and food- borne parasites are discussed.

Keywords: Keywords: Benzaldehydes; Protozoal pathogens; Structure-activity relationship