¹Southern Federal University; ²Rostov State Medical University; Rostov-on-Don, the Russian Federation
*Corresponding author: Ekaterina S. Levitskaya, PhD. Rostov State Medical University, Rostov-on-Don, Russia. E-mail: es.med@mail.ru
Published: September 12, 2016. DOI: 10.21103/Article6(3)_OA15
The aim of the present study was to investigate biological properties of the novel nitrobenzoxadiazole derivative 7-(1-methyl-3-pyrrolyl-)-4,6-dinitrobenzofuroxan.
Materials and Methods: We used a bioluminescent test based on a set of lux-biosensors, which are genetically modified E.coli strains able to react on different types of factors that can induce an SOS-response with light emission. The spontaneous and induced mutation frequencies of antibiotic resistance in E. coli were determined by methods of classical genetics of microorganisms.
Results: 7-(1-methyl-3-pyrrolyl-)-4,6-dinitrobenzofuroxan demonstrated inhibition of SOS-response in a biosensor model system and significantly reduced the frequency of spontaneous mutations and mutations induced by ciprofloxacin of antibiotic resistance.
Conclusion: Based on our data, we can recommend using compound-1 as a starting point for the development of drugs that block mutagenesis associated with the emergence of antibiotic-resistant bacteria.
- Khachatryan N, Vabishchevich NK, Ohinko LV, Muslimov BG. The place of modern fluoroquinolones of III generation in the treatment of diffuse peritonitis. Medical Advice. 2013; (5-6):46-52. [In Russian]
- Rafalskiy V. Dovgan E., Hodnevich L. Fluoroquinolones in the treatment of urinary tract: What changes uropathogens antibiotic resistance? Doctor. 2012;2:36-42. [In Russian]
- Cirz RT, Chin JK, Andes DR, de Crécy-Lagard V, Craig WA, Romesberg FE.Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biol. 2005;3(6):e176.
- Radman M. SOS repair hypothesis: Phenomenology of an inducible DNA repair which is accompanied by mutagenesis. Basic Life Sci. 1975; 5A:355–367.
- Wigle TJ, Sexton JZ, Gromova AV, Hadimani MB, Hughes MA, Smoth JR, et al. Inhibitors of RecA activity discovered by high-throughput Screening: cell-permeable small molecules attenuate the SOS response in Escherichia coli. J Biomol Screen. 2009; 14(9):1092–101.
- Lee AM, Ross CT, Zeng BB, Singleton SF. A molecular target for suppression of the evolution of antibiotic resistance: inhibition of the Escherichia coli RecA protein by N(6)-(1-naphthyl)-ADP. J Med Chem 2005; 48(17):5408-11.
- Wigle TJ, Lee AM, Singleton SF. Conformationally selective binding of nucleotide analogues to Escherichia coli RecA: a ligand-based analysis of the RecA ATP binding site. Biochemistry 2006; 45(14):4502-13.
- Wigle TJ, Singleton SF. Directed molecular screening for RecA ATPase inhibitors. Bioorg Med Chem Lett 2007; 17(12): 3249-53
- Cline DJ, Holt SL, Singleton SF. Inhibition of Escherichia coli RecA by rationally redesigned N-terminal helix. Org Biomol Chem 2007; 5(10):1525-8.
- Lee AM, Singleton SF. Inhibition of the Escherichia coli RecA protein: zinc(II), copper(II) and mercury(II) trap RecA as inactive aggregates. J Inorg Biochem. 2004; 98(11): 1981-6.
- Sexton JZ, Wigle TJ, He Q, Hughes MA, Smith GR, Singleton SF, et al. Novel inhibitors of E. coli RecA ATPase activity. Curr Chem Genomics. 2010; 4:34-42.
- Prazdnova EV, Kharchenko EY, Chistyakov VA, Semenyuk YuP, Morozov PG, Kurbatov SV, Chmyhalo VK. Synthesis and biological properties of new nitrobenzoxadiazole derivatives. Biol Med (Aligarh). 2015; 7(3): BM-123-15.
- Ushakov VY. DNA repair SOS-system in bacteria (review). Perm University Herald. Series: Biology. 2010; 2:19-30. [In Russian]
- Michel B. After 30 years of study, the bacterial SOS response still surprises us. PloS Biol. 2005; 3(7):e255.
- Manukhov IV, Kotova VIu, Mal'dov DK, Il'ichev AV, Bel'kov AP, Zavil'gel'skiĭ GB. Induction of oxidative stress and SOS response in Escherichia coli by plant extracts: the role of hydroperoxides and the synergistic effect of simultaneous treatment with cisplatinum. Mikrobiologiia. 2008;77(5):590-7. [Article in Russian]
- Chistyakov VA. et al. Synthesis and biological properties of nitrobenzoxadiazole derivatives as potential nitrogen (ii) oxide donors: SOX induction, toxicity, genotoxicity, and DNA protective activity in experiments using Escherichia coli-based lux biosensors Russian Chemical Bulletin. 2015:64(6):1369-1377.
- Semina NA, Sidorenko SV, Rezvan S P. Determination of the microorganisms sensitivity to antibiotics Guidelines ,MUK. 2004; 4:1890-1904.
- Shakhov AG, Sashnina LY, Lebedev MI, Lebedeva EV. Study of resistance of bacterial pathogens of gastrointestinal and respiratory diseases of pigs to antimicrobial preparations. Rep Russ Acad Agric Sci. 2011;2:53-55. [In Russian]
- Salmanov AG, Marievsky VF. Antibiotic resistance of nosocomial strains of Staphylococcus Aureus in Ukraine: results of a multicenter study. Surg News. 2013; 21(4): 78-83. [In Russian]
The fully formatted PDF version is available.
Int J Biomed. 2016;6(3):228-232. © 2016 International Medical Research and Development Corporation. All rights reserved.