Acute and subchronic toxicity studies of the original drug FS-1

Abstract

Interest in iodine complexes has increased significantly in recent years because of their wide spectrum of biological activity. The FS-1 is an ion nanostructured complex formed by proteins and/or polypeptides, carbohydrates, salts of alkali and alkaline earth metals with intercalated iodine. Patented in 2014, it is intended for the treatment of infectious diseases of bacterial origin including nosocomial infections and multidrug resistant tuberculosis. The aim of the study was to determine its acute and subchronic toxicity. The study of acute and subchronic toxicity was performed on adult Wistar rats according to OECD guidelines. The data on acute toxicity showed LD50 > 2,000 mg/kg after a single intragastric administration. Twenty-eight days of FS-1 administration at a dose of 500 mg/kg resulted in toxic effects. At a dose of 250 mg/kg, the toxic effects were temporary and a return to normal followed after the recovery period. Doses of 100 mg/kg had no adverse effects on the rats.

Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

“…The hypothesis of fitness cost aggravation is in line with previous scientific reports on this topic. It was demonstrated that many drug resistance mutations in prodrug activators made the mutants more sensitive to the oxidative stress caused by the iodine containing FS-1 [33,34]. To the best of our knowledge, this work was the first experimental confirmation of the drug induced antibiotic resistance reversion by the induced synergy mechanism that had been predicted theoretically in the recent publication [3].…”

Assembly of Complete Genome Sequences of Negative-Control and Experimental Strain Variants of Staphylococcus aureus ATCC BAA-39 Selected under the Effect of the Drug FS-1, Which Induces Antibiotic Resistance Reversion

“…The iodine-containing nanomolecular complex FS-1 induces a reversion of drug-resistant bacteria into sensitive phenotypes (1). FS-1 was designed to supplement antibiotic treatment therapy against drug-resistant tuberculosis (2) and has been shown to be successful against multidrug-resistant Staphylococcus aureus (MRSA) (3). To investigate the molecular mechanisms of this phenomenon, Staphylococcus aureus ATCC BAA-39 was used as a model organism.…”

Genomic Insight into Mechanisms of Reversion of Antibiotic Resistance in Multidrug Resistant Mycobacterium tuberculosis Induced by a Nanomolecular Iodine-Containing Complex FS-1

“…More than 1,000 putative drug resistance mutations have been predicted (Sandgren et al, 2009 ). Over the last 40 years, no new antibiotics against tuberculosis have been developed and only recently several new drugs have been proposed: Bedaquiline (Mahajan, 2013 ), Delamanid (Gupta et al, 2015 ) and FS-1 (Ilin and Kulmanov, 2014 ; Kalykova et al, 2016 ). However, resistance to Bedaquiline and Delamanid has already been reported (Hoffmann et al, 2016 ).…”

“…However, resistance to Bedaquiline and Delamanid has already been reported (Hoffmann et al, 2016 ). FS-1 is an iodine-containing nanomolecular complex showing an antimicrobial effect (Kalykova et al, 2016 ). Active units of FS-1 are aggregated micelles containing complexes of triiodide molecules coordinated by metal ions and integrated into a dextrin-polypeptide moiety.…”