Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition

Abstract

Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L−1) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32–138 µM (8–32 mg L−1). These compounds also displayed moderate inhibitory effects on Klebsiella and Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and cytotoxicity assays were used to evaluate these compounds. Of particular note was their ability to inhibit mycobacterial drug efflux and biofilm formation, while maintaining a high selectivity towards M. tuberculosis H37Rv. These results suggest that methyl disulfides are novel scaffolds which could lead to the development of new drugs against tuberculosis (TB).

Baicalin Inhibits Biofilm Formation and the Quorum-Sensing System by Regulating the MsrA Drug Efflux Pump in Staphylococcus saprophyticus

“…It has been reported that increasing resistance is associated with active efflux in bacterial biofilms (Van Acker and Coenye, 2016;Danquah et al, 2018). Baugh et al demonstrated that numerous functional efflux pumps give rise to biofilm matrix expression in Salmonella Typhimurium and that the addition of a variety of efflux inhibitors inhibited biofilm formation (Baugh et al, 2012).…”

“…QS is a process of bacterial cell-cell communication that allows bacteria to sense cell density and change bacterial gene expression patterns to alter bacteria group behaviors at high cell numbers (Rutherford and Bassler, 2012;Camilli and Bassler, 2006). This cross-talk between bacteria is believed to be essential for the establishment of bacterial biofilms and bacterial biofilm infection (Danquah et al, 2018). QS regulates the expression of genes encoding virulence factors involved in a range of toxins, adhesion molecules, and compounds that influence immune function.…”

Synthesis and mycobacterial evaluation of 5‐substituted‐6‐acetyl‐2‐amino‐7‐methyl‐5,8‐dihydropyrido‐[2,3‐d]pyrimidin‐4(3H)‐one derivatives

“…VP, a known potent efflux pump inhibitor, and an inhibitor‐free culture were used as the positive and negative controls respectively. The experiments were performed in triplicate and the graph was plotted using the average of the readings …”

Antimicrobial Agents: Antibacterial Agents, Anti-biofilm Agents, Antibacterial Natural Compounds, and Antibacterial Chemicals

“…Lemon balm, Melissa officinalis (family: Lamiaceae) and tea tree, Melaleucae alternifolia (family: Myrtaceae) are taken as herb teas and tea tree oil is applied as ointment [51]. Garlic, Allium sativum (family: Alliaceae) have antimicrobial and antiseptic properties and is used for respiratory tract infections [48,49] .…”

“…Natural products have the ability to provide diversity, complexity, novelty and new scaffolds with various chiral centers, rings, bridges and functional groups in the molecule [47]. They differ from synthetic compounds by having more oxygen atoms and stereochemical elements such as polycycle (often bridged) carbon skeletons [48,49]. Some of the most valuable products and promising leads in oncology were naturally derived or naturally inspired.…”