In vitro antibacterial activities of p-toluenesulfonyl-hydrazinothiazoles and hydrazinoselenazoles against multi-drug resistant Gram-negative phenotypes

Bacterial multidrug resistance represents a major problem in the treatment of infectious diseases. In the present study, we tested a panel of bacterial strains including both reference ATCC strains and MDR phenotypes expressing active efflux pumps [4, 5, 22]. In fact, tripartite drug efflux pumps, mainly those clinically reported as AcrAB–TolC in Enterobacteriaceae or as MexAB–OprM in P. aeruginosa tested in the present study, play a key role in multidrug resistance of pathogenic Gram-negative bacteria [23, 24]. p-Toluenesulfonyl-hydrazinothiazoles and hydrazinoselenazoles are synthetic compounds that previously displayed good anticancer, analgesic and anti-inflammatory activities [8–11]. Herein, we investigated the ability of such compounds to combat MDR Gram-negative bacteria expressing active efflux pumps. As results, it was found that hydrazinoselenazoles were much more active than p-toluenesulfonyl-hydrazinothiazoles. However, all the tested chemicals were substrates of bacterial efflux pumps. Interestingly, when efflux pumps were blocked by EPI, significant increase of the activity of three compounds 12, 14 and 16 was observed. More importantly, the obtained activity was better than that of the reference drug chloramphenicol in many cases (Table 1), suggesting that the three compounds can be used in combination with PA?N to fight bacterial infections involving MDR phenotypes. The antimicrobial activity of a compound has been defined as significant when MIC is below 10 mg/L, moderate when 10 mg/L??MIC??100 mg/L or low when MIC??100 mg/L [25, 26]. In this study, the MIC values below 10 mg/L was noted with hydrazinoselenazoles 12, 14 and 16 on 43.8 %, 62.5 % and 100 % tested bacterial strains when they were tested in the presence of EPI, highlighting their possible use in combination with PA?N in the control of MDR bacterial infections.

Regarding the involvement of MDR bacteria in treatment failures and the re-emergence of infectious diseases [1, 27, 28], these findings can be considered very promising. In fact, Pseudomonas aeruginosa is an important nosocomial pathogen highly resistant to clinically used antibiotics, causing a wide spectrum of infections and leading to substantial morbidity and mortality [29] and was found sensitive to the three compounds. MDR Enterobacteriaceae, including K. pneumoniae, E. aerogenes, P. stuartii and E. coli, have also been classified as antimicrobial-resistant organisms of concern in healthcare facilities [28, 30].