High-throughput identification of antibacterials against methicillin-resistant Staphylococcus aureus (MRSA) and the transglycosylase

Screening a Commercial Library of Pharmacologically Active Small Molecules against Staphylococcus aureus Biofilms

“…It is in the salicylanilide family of compounds (a large family with a range of medical applications) and is an analogue of closantel. The antimicrobial activity of some derivatives and analogues of niclosamide has been documented (27,28). It has received increased attention in recent years due to its anticancer activity (29) and antidiabetic activity (30), highlighting its potential as a candidate for repurposing.…”

A facile, metal-free, oxidative coupling of new 6-(hetero)aryl-[1,2,5]-oxadiazolo[3,4-b]pyrazines with pyrroles, indoles and carbazoles

“…The reactions proved to proceed as a classical nucleophilic aromatic substitution of hydrogen (SN H ) via the intermediacy of σ H -adducts, 5-(hetero)aryl-6-substituted-4,5-dihydro- [1,2,5]oxadiazolo [3,4-b]pyrazin-4-ium salts, and subsequent oxidation of these dihydro compounds by air oxygen (Scheme 3). While some pyrazine derivatives 10,[13][14][15][16][17] [3,4-b]pyrazine (1a) with pyrrole (7), indole (11), 1-ethyl-1H-indole (13) and carbazole (17) in the presence of various catalysts (Table 1). It has been established that the best yeild of the SN H -product derived from the reaction 1a with pyrroles is reached on using CF3COOH, whereas use of BF3·Et2O and CH3COOH leads to a complex multi-component mixture with a large amount of tar.…”

Salicylanilide carbamates: Promising antibacterial agents with high in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA)

“…78 Nowadays, SALs are well-known organic compounds exhibiting a 79 broad spectrum of interesting biological activities, such as anthelmintic (Bartram et al, 2012), antibacterial (Cheng et al,81 2010; Mollaghan et al, 2011;Pauk et al, 2013), antifungal 82 (Vinsova et al, 2014), antimycobacterial (Pauk et al, 2013) and 83 antiviral (Liu et al, 2008;Wu et al, 2004), among others. SALs have 84 been described to affect a wide range of targets (Brown et al, 2008;85 Cheng et al, 2010;Hlasta et al, 1998;Kratky et al, 2012;Liechti 86 et al, 2004;Liu et al, 2008;Macielag et al, 1998;Wu et al, 87 2004), although the appropriate mechanism of action responsible 88 for overall biological activities of these compounds has not been 89 proposed so far. SALs have been found to inhibit the 90 two-component regulatory systems (TCS) of bacteria (Hlasta 91 et al, 1998;Macielag et al, 1998).…”

“…Thus, 104 SALs seem to be promising candidates of antibacterial agents, 105 which could be a solution to the resistance challenges. 106 To assure higher antibacterial and especially antimycobacterial 107 activity, SALs and their derivatives were chemically modified in the 108 recent years (Brown et al, 2008;Cheng et al, 2010;Ferriz et al, 109 2010;Imramovsky et al, 2009Imramovsky et al, , 2011aKratky et al, 2012;Liechti 110 et al, 2004;Liu et al, 2008;Mollaghan et al, 2011;Pauk et al, 111 2013; Vinsova et al, 2007Vinsova et al, , 2014Waisser et al, 2003). The synthe-112 sis of a series of novel SAL N-alkylcarbamates (see Table 1 for the 113 general structure) was described previously (Ferriz et al, 2010), 114 and their antimycobacterial (Ferriz et al, 2010), 115 photosynthesis-inhibiting (Imramovsky et al, 2011b) All the series of novel SAL N-alkylcarbamates were synthesized 131 previously, and the synthetic pathway of these compounds was 132 described recently (Ferriz et al, 2010).…”

“…The latest studies 95 specified them also as selective inhibitors of interleukin-12p40 96 production that plays a specific role in initiation, expansion and 97 control of cellular response to tuberculosis (Brown et al, 2008). 98 Furthermore, SALs have been determined as inhibitors of some 99 bacterial enzymes, such as transglycosylases from S. aureus (but 100 not from Mycobacterium tuberculosis) in the cell wall biosynthesis 101 (Cheng et al, 2010). Inhibition of isocitrate lyase and methionine 102 aminopeptidase has been described to be involved in the antimy-103 cobacterial activity of SAL derivatives (Kratky et al, 2012).…”