Biological evaluation of diphenyleneiodonium chloride (DPIC) as a potential drug candidate for treatment of non-tuberculous mycobacterial infections

Abstract

DPIC exhibits all properties to be repositioned as a novel anti-mycobacterial therapy and possesses a potentially new mechanism of action. Thus, it can be projected as a potential new therapeutic against ever-increasing non-tuberculous mycobacterial infections.

In vitro and in vivo activity of Gepotidacin against drug-resistant mycobacterial infections

“…Bactericidal activity of GEPO was assessed by the time-kill method (16). M. fortuitum ATCC 6841, M. abscessus ATCC 19977, and Mtb H37Rv ATCC 27294 were diluted to achieve ~10 6 CFU/mL in a total volume of ~0.3 mL and added to 96 well plates along with GEPO and controls at 1x, and 10x MIC followed by incubation at 37 0 C for 7 days for slow-growing mycobacteria and 48 h for NTM.…”

Update on Drug-Repurposing: Is it Useful for Tackling Antimicrobial Resistance?

“…In the context of repurposing drugs for antimicrobial activity, there has been increasing reports of approved drugs being identified for their antimicrobial activity. Some of the more prominent examples include auranofin, an antirheumatoid arthritis drug, which was granted an orphan drug status in 2012 by US FDA, repurposed as a broad spectrum antimicrobial and has undergone a clinical trial for the treatment of gastrointestinal protozoa (NCT02736968) [7]; chlorocyclizine, an anti-allergic as an antiviral [8]; eflornithine, an antitumor agent repurposed for the treatment of human African trypanosomiasis [9]; miltefosine, another antitumor agent used to target visceral leishmaniasis [10]; niclosamide, an anthelminthic drug repurposed for antiviral and antibacterial activity [11,12]; pentamidine, an antiprotozoal repurposed as an antibacterial [13]; sertraline, an antidepressant as an antifungal [14]; tamoxifen, an antitumor as an antifungal [15]; ivacaftor, an anticystic fibrosis drug as an antibacterial [16]; DPIC, an nitric oxide synthase inhibitor as a broad spectrum antibacterial [17,18]; disulfiram, an anti-alcoholic drug repurposed as an antibacterial [19,20]; and ebelsen, repurposed as an antibacterial [21], among others. Despite these positive efforts, there are significant hurdles encountered in a successful translational implementation of repurposing drugs for antimicrobial activity such clinical pharmacology, pharmacokinetics, high cost of clinical trials and intellectual property rights [22].…”