Acute, Multiple-Dose Dermal and Genetic Toxicity of Nu-3: A Novel Antimicrobial Agent

Abstract

Nu-3 [butyl-phosphate-5′-thymidine-3′-phosphate-butyl] is a modified nucleotide that has been shown to have antimicrobial activity against a range of bacteria including Pseudomonas aeruginosa. However, data on the toxicological profile of Nu-3 are still lacking. In the present study, the toxicity of Nu-3 was evaluated by the following studies: acute oral toxicity, dermal and mucous membrane irritation, multiple-dose toxicity and genotoxicity in vivo and vitro. The acute oral toxicity test in mice showed that Nu-3 had an LD50 of 2001mg/kg body weight. The irritation tests on rats revealed that Nu-3 was not irritant, with an irritation scoring of 0. The multiple-dose toxicity study in rats showed that Nu-3 did not cause significant changes in histology, selected serum chemistry, and hematological parameters compared to the controls. Rats administrated with multiple-doses of Nu-3 showed no visible toxic symptoms. Both in vitro and in vivo, Nu-3 exhibited no notable genetic toxicity. Overall, the data suggest that Nu-3 is hypotoxic or nontoxic antimicrobial compound that warrants being further developed for treating Pseudomonas aeruginosa infection.

Antimicrobial activity and mechanism of action of Nu-3, a protonated modified nucleotide

“…Previous studies demonstrated that Nu-3 was efficacious in the treatment of burn-wound infections by Pseudomonas aeruginosa in mice [ 6 ]. Subsequent studies revealed that there was no chronic toxicity to healthy mouse skin when Nu-3 was applied topically [ 7 ], indicating that Nu-3 has a favorable toxicological profile for use as a topical antibiotic. In order to further explore how wide the spectrum of Nu-3 antibacterial activity is, MIC and time-kill experiments were performed with a wide range of Gram-positive and Gram-negative bacteria, including some hospital isolates of meticillin-resistent Staphylococcus aureus (MRSA) and meticillin-susceptible Staphylococcus aureus (MSSA).…”

Safety Assessment of a Nucleoside Analogue FNC (2’-deoxy-2’- β-fluoro-4’-azidocytidine ) in Balb/c Mice: Acute Toxicity Study

“…of FNC (Zhang et al, 2017). FNAs behaves unorthodoxly in case of liver toxicity, where in some studies NAs show significant toxicity to the liver at very low concentration (Sun et al, 2010), and in other no toxicity even at very high concentration (Chen et al, 2013;Inkoom et al, 2020). Organs like the spleen, heart, brain, and lungs are other sites affected by the drug, due to drug accumulation (Jiang et al, 2019;Shi et al, 2013).…”