Beta-lapachone: Natural occurrence, physicochemical properties, biological activities, toxicity and synthesis

Identification of Antimotilins, Novel Inhibitors of Helicobacter pylori Flagellar Motility That Inhibit Stomach Colonization in a Mouse Model

“…Two compounds, Active1 and Active2, exhibited a strong activity against flagella-associated functions in the primary screen and might represent active patho-blocker compounds. Active1, which also had very strong antibacterial effects on H. pylori , belonged to the family of β-lapachones, which have been described as canonical strong antibacterial natural compounds from Lapacho tree bark active on various bacterial species and parasites long ago ( 41 – 46 ). One validated cellular (metabolic) target of β-lapachone is the NAD(P)H:quinone oxidoreductase-1 (NQO1) subunit of membrane respiratory complex I ( 47 ), which has led to the proposition of using lapachones in a variety of indications, including the treatment of tumors, parasites, fungi or bacterial infections, as its target is ubiquitous and essential in bacteria ( 46 ).…”

“…Active1, which also had very strong antibacterial effects on H. pylori , belonged to the family of β-lapachones, which have been described as canonical strong antibacterial natural compounds from Lapacho tree bark active on various bacterial species and parasites long ago ( 41 – 46 ). One validated cellular (metabolic) target of β-lapachone is the NAD(P)H:quinone oxidoreductase-1 (NQO1) subunit of membrane respiratory complex I ( 47 ), which has led to the proposition of using lapachones in a variety of indications, including the treatment of tumors, parasites, fungi or bacterial infections, as its target is ubiquitous and essential in bacteria ( 46 ). We performed direct motility (taxis) assays with Active1, which strongly inhibited motility and targeted motility at low concentrations after short exposure times ( Fig.…”

“…Several primary actives had low antibacterial MIC values and acted on H. pylori probably via metabolic inhibition. For further studies, we selected one small molecule, named Active1 (β-lapachone, a 2,4-naphthoquinone) long-known to have antibacterial effects on a variety of species ( 44 , 46 ), but not yet characterized to be active against H. pylori . β-lapachone derivatives, due to their cell-killing activity, are currently being further developed as anticancer agents ( 45 , 47 , 72 ) and were also strongly active against H. pylori in our hands.…”

Beta-Lapachone Attenuates BMSC-Mediated Neuroblastoma Malignant Transformation by Inhibiting Gal-3/Gal-3BP/IL6 Axis

“…LPC is a pleiotropic natural product, which has attracted much attention because of its strong antitumor activity in a variety of tumors ( Gomes et al, 2021 ; Gong et al, 2021 ). LPC has limited therapeutic use because of its narrow treatment window, poor water solubility and high toxicity ( Gomes et al, 2021 ).…”

“…LPC is a pleiotropic natural product, which has attracted much attention because of its strong antitumor activity in a variety of tumors ( Gomes et al, 2021 ; Gong et al, 2021 ). LPC has limited therapeutic use because of its narrow treatment window, poor water solubility and high toxicity ( Gomes et al, 2021 ). At present, a large number of studies focus on ameliorating the defects of LPC itself through formulation improvement or structural modification optimization, which makes it possible to regain clinical application ( Blanco et al, 2007 ; Park et al, 2016 ; Jardim et al, 2017 ).…”