Evaluation of minor groove binders (MGBs) as novel anti-mycobacterial agents and the effect of using non-ionic surfactant vesicles as a delivery system to improve their efficacy

Abstract

MGB anti-mycobacterial activities together with non-toxic properties indicate that MGB compounds constitute an important new class of drug/chemical entity, which holds promise in future anti-TB therapy. Furthermore, the ability of NIVs to better deliver entrapped MGB compounds to an intracellular Mtb infection suggests further preclinical evaluation is warranted.

Selective in vitro anti-cancer activity of non-alkylating minor groove binders

“…11 Importantly, our S-MGBs do not possess any alkylating moieties and we hypothesise that their mechanism of action against cancer cells is similar to that observed in our ongoing studies of anti-bacterial and anti-parasitic S-MGBs which suggest non-covalent interruption of DNA functions. [19][20][21] Moreover, we have previously demonstrated that S-MGBs 4, 74 and 317 do bind to DNA giving ΔTms of 7, 4 and 7 o C, respectively. 9 However, it was important to establish whether these lead anti-cancer S-MGBs induce significant DNA damage or not and thus whether these might suffer from similar toxicity issues as alkylating anti-cancer MGBs.…”

Minor Groove Binders MGBs: A Mini Review

“…3.1.Summary of a study of MGBs as drugs in the fight against the Mycobacterium tuberculosis (Mtb) disease [51]: Mycobacterium tuberculosis (Mtb), is a crucial subject as it is among the top infectious illnesses around the world. The world health organisation in 2016 [39] reported that TB killed around 1.8 million people in 2015, that is an increase from 1.5 million deaths in 2014 [40] .…”

“…There are several reports showing NIVs to be a promising inhalable drug delivery system for the treatment of pulmonary aspergillosis with aerosolized amphotericin. Amphotericin B/NIV administration lowered fungal lung infection when it was compared with amphotericin B solution alone [48][49][50][51][52].…”

“…-GFP South African researchers [51] screened 96 MGBs (supplied to them by the Department of Pure and Applied Chemistry at the University of Strathclyde, Glasgow) for their anti-mycobacterial activity against GFP-labelled H37Rv Mtb in liquid broth culture using a 96-well plate assay. Relative fluorescence was measured at 0, 4, 8, 10 and 12 days in broth culture of MGBs (these were serially diluted from 25 to 0.19 µM) to determine the MIC99 of MGBs these compounds should kill 99% of Mtb.…”

Novel antibiotic mode of action by repression of promoter isomerisation

“…These structural variants retained DNAbinding and anti-Gram-positive activity but lacked human toxicity [6]. One of these, MGB-BP-3 ( Figure 1a found to be active against a wide variety of pathogens and some cancer cell lines [7][8][9][10][11]. Antibacterial activity of MGB-BP-3 is confined to Gram-positive bacteria and dose response curves show a steep decrease in viability over a narrow concentration range, suggesting a catastrophic failure in the bacterium rather than an interaction with a single receptor typified by a sigmoidal dose-response curve.…”