Comprehensive biological evaluation of Rheinal as a potent antimicrobial, alone and in combination with gentamicin and minocycline targeting MDR S. aureus in vitro and in vivo.

Antimicrobial resistance is recognized as a threat to healthcare systems worldwide and consequently, discovery and development of new antimicrobials is a top priority. Natural products and their derivatives have historically been an excellent source of antimicrobials. In this context, anti-bacterial activity of synthesized natural product derivative, Rheinal, was assessed against a panel of Gram-positive and Gram-negative bacterial pathogens where it exhibited potent bactericidal activity against S. aureus with MIC 0.125 μg/mL, including against multidrug-resistant clinical isolates, irrespective of the drug-resistant profile exhibited by them. Rheinal was found to be safe at concentrations exceeding 512-fold of MIC against eukaryotic cells and synergized with gentamicin, daptomycin and minocycline against S. aureus ATCC 29213. Rheinal also acted against pre-formed biofilm, displayed better post-antibiotic effect than vancomycin and exhibited powerful activity against S. aureus in murine skin infection model. Taken together, this study describes the excellent antibacterial properties exhibited by Rheinal under both in vitro and in vivo conditions against S. aureus.