Pharmacological Exploitation of Non-Steroidal Anti-inflammatory Drugs as Potential Sources of Novel Antibacterial Agents

Abstract

The ever-increasing threat of bacterial infections and antimicrobial resistance calls for a global effort to deal with this problem. This fast and universal dissemination of antimicrobialresistant bacterial strains resulted in the diminution of therapeutic alternatives for various infectious diseases. Besides, the unaffordability of efficacious antimicrobials coupled with the occurrence of unpleasant adverse effects calls for the exploration of alternative agents with possible antibacterial effect. All these challenges of microbes have posed new drives to the scientific communities. Researchers are now assessing the possible alternative antimicrobial agents for fighting bacterial infections and antimicrobial resistance. Therefore, this review emphasizes on the role of nonsteroidal anti-inflammatory agents as potential sources of novel antibacterial agents on which preliminary studies and randomized controlled trials had been performed. The review also deals with the possible antibacterial mechanism of actions and the likely effects of non-steroidal antiinflammatory drugs when combined along with conventional antibacterial agents.

Non-antibiotic pharmaceuticals promote the transmission of multidrug resistance plasmids through intra- and intergenera conjugation

“…In addition, it has been documented that these non-antibiotic pharmaceuticals can have antimicrobial effects in vivo. NSAIDs have been assessed as potential sources of novel antibacterial agents in vivo [ 80 ]. For example, diclofenac protected mice from virulent Salmonella infection [ 81 ], and ibuprofen demonstrated antimicrobial activity against Candida albicans in mouse kidney models [ 82 ].…”

Microbial biofilms and some aspects of anti-inflammatory drug use

“…The influence of pro-inflammatory interleukins in the development of urogenital infections caused by E. coli has been studied in detail [53,54]. Yimer et al [55] emphasize the role of NSAIDs as potential sources of new antibacterial agents, with which the previous studies and randomized controlled trials have been conducted. The review also considers the possible antibacterial mechanism of action and NSAIDs' likely effectiveness in combination with traditional antibacterial drugs [55].…”

“…Yimer et al [55] emphasize the role of NSAIDs as potential sources of new antibacterial agents, with which the previous studies and randomized controlled trials have been conducted. The review also considers the possible antibacterial mechanism of action and NSAIDs' likely effectiveness in combination with traditional antibacterial drugs [55]. In studying the mechanism of action of NSAIDs on bacteria, it was found that some NSAIDs are the substrates, to which the pumping mechanisms at efflux effects among gram-negative bacteria are directed.…”

Repurposing anti-inflammatory drugs for fighting planktonic and biofilm growth. New carbazole derivatives based on the NSAID carprofen: synthesis, in silico and in vitro bioevaluation

“…Thus, 2-((3-(3,6-dichloro- 9H -carbazol-9-yl)-2-hydroxypropyl)amino)-2-(hydroxymethyl)propane-1,3-diol ( Figure 1 - compound 10) that reduces the transmembrane potential of Gram-positive and Gram-negative bacteria and causes mislocalization of essential membrane-associated proteins, provides new opportunities for the development of potent broad-spectrum antimicrobial agents ( Eun et al., 2012 ). Another mechanism supports the idea that carbazole derivatives can interact with bacterial DNA replication and repair ( Zhang et al., 2018 ), by inhibiting the DNA polymerase ( Foxman, 2010 ), being reported to inhibit the growth of different Gram-positive and Gram-negative bacteria, such as B. cereus , Staphylococcus aureus, Listeria monocytogenes, Mycobacterium tuberculosis, M. bovis, M. neoaurum, M. smegmatis, Salmonella choleraesuis, Enterobacter aerogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, Helicobacter pylori ) ( Lee et al., 2014 ; Addla et al., 2016 ; Yimer et al., 2018 ).…”