Evaluation of Antiseptic Drug Candidate Pyridosept in Preclinical in Vitro Studies

Abstract

Introduction: This work provides preclinical in vitro studies of an innovative antimicrobial agent named pyridosept, belonging to the quaternary bis-ammonium salts and synthesized on the base of pyridoxine. Since the wide spread of pathogens with tolerance to both antibiotics and antiseptics challenges the development of new antimicrobials providing high efficiency against fungi and microorganisms with multiple resistance.

Method: This work presents in vitro studies of pyridosept, such as antibacterial and anti-fungal activities (determination of minimal inhibitory concentration and quantitative suspension test method), as well as antibacterial activity of metal surface test, sporicidal and spermicidal activities, formation of resistance (to bacteria and fungi), Skin-PAMPA (study of membrane transdermal permeability), mutagenicity assays (in Ames test and OS-chromotest), cytotoxicity (MTT-assay) and comet assay in human skin fibroblasts.

Results: Pyridosept demonstrates advantageous antibacterial and antifungal activity in both suspension and metal surface tests; it has anti-SARS-CoV-2, spermicidal and sporicidal activities (comparable to chlorhexidine digluconate). On the other hand, it demonstrates a low frequency of bacterial resistance development (no more than 2-4-fold in- crease of the MIC in 30 passages, with MIC values fluctuating within 1-8 μg/ml for Gram-positive bacteria and 4-32 μg/ml for Gram-negative bacteria) and membrane transdermal permeability (Skin-PAMPA, 500-fold less compared to progesterone). While cytotoxicity (in MTT- and comet assay) of pyridosept is comparable with those for bezalkonium chloride and chlorhexidine, our results suggest that pyridosept represents an advantageous structure for the design of new antiseptics.

Conclusion: The information obtained during the studies demonstrated that pyridosept has a good efficacy and safety profile, which allows us to consider it as a potential anti-septic and disinfectant, for which it is necessary to conduct additional in vivo studies.

Keywords: Pyridosept; antiseptics; benzalkonium chloride; chlorhexidine digluconate; in vitro.; miramistin.