Author:
Tozar Tatiana,Santos Costa Sofia,Udrea Ana-Maria,Nastasa Viorel,Couto Isabel,Viveiros Miguel,Pascu Mihail Lucian,Romanitan Mihaela Oana
Abstract
AbstractAntibiotic resistance became an increasing risk for population health threatening our ability to fight infectious diseases. The objective of this study was to evaluate the activity of laser irradiated thioridazine (TZ) against clinically-relevant bacteria in view to fight antibiotic resistance. TZ in ultrapure water solutions was irradiated (1–240 min) with 266 nm pulsed laser radiation. Irradiated solutions were characterized by UV–Vis and FTIR absorption spectroscopy, thin layer chromatography, laser-induced fluorescence, and dynamic surface tension measurements. Molecular docking studies were made to evaluate the molecular mechanisms of photoproducts action against Staphylococcus aureus and MRSA. More general, solutions were evaluated for their antimicrobial and efflux inhibitory activity against a panel of bacteria of clinical relevance. We observed an enhanced antimicrobial activity of TZ photoproducts against Gram-positive bacteria. This was higher than ciprofloxacin effects for methicillin- and ciprofloxacin-resistant Staphylococcus aureus. Molecular docking showed the Penicillin-binding proteins PBP3 and PBP2a inhibition by sulforidazine as a possible mechanism of action against Staphylococcus aureus and MRSA strains, respectively. Irradiated TZ reveals possible advantages in the treatment of infectious diseases produced by antibiotic-resistant Gram-positive bacteria. TZ repurposing and its photoproducts, obtained by laser irradiation, show accelerated and low-costs of development if compared to chemical synthesis.
Publisher
Springer Science and Business Media LLC
Reference60 articles.
1. Njogu, P. M., Guantai, E. M., Pavadai, E. & Chibale, K. Computer-aided drug discovery approaches against the tropical infectious diseases malaria, tuberculosis, trypanosomiasis, and leishmaniasis. ACS Infect. Dis. 2, 8–31 (2016).
2. Butcher, E. C., Berg, E. L. & Kunkel, E. J. Systems biology in drug discovery. Nat. Biotechnol. 22, 1253–1259 (2004).
3. Law, G. L., Tisoncik-Go, J., Korth, M. J. & Katze, M. G. Drug repurposing: a better approach for infectious disease drug discovery?. Curr. Opin. Immunol. 25, 588–592 (2013).
4. Radhakrishnan, V., Ganguly, K., Ganguly, M., Dastidar, S. G. & Chakrabarty, A. N. Potentiality of tricyclic compound thioridazine as an effective antibacterial and antiplasmid agent. Indian J. Exp. Biol. 37, 671–675 (1999).
5. Costa, S. S., Viveiros, M., Rosato, A. E., Melo-Cristino, J. & Couto, I. Impact of efflux in the development of multidrug resistance phenotypes in Staphylococcus aureus. BMC Microbiol. 15, 232 (2015).
Cited by
22 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献