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Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis
Makarov, V.,Manina, G.,Mikusova, K.,Mollmann, U.,Ryabova, O.,Saint-Joanis, B.,Dhar, N.,Pasca, M. R.,Buroni, S.,Lucarelli, A. P.,Milano, A.,De Rossi, E.,Belanova, M.,Bobovska, A.,Dianiskova, P.,Kordula American Association for the Advancement of Scienc 2009 Science Vol.324 No.5928
<P>New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase as a major BTZ target. Inhibition of this enzymatic activity abolishes the formation of decaprenylphosphoryl arabinose, a key precursor that is required for the synthesis of the cell-wall arabinans, thus provoking cell lysis and bacterial death. The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB.</P>
Characterisation and Durability of a Vitrified Wasteform for Simulated Chrompik III Waste
Walling, Sam A.,Gardner, Laura J.,Pang, H.K. Celine,Mann, Colleen,Corkhill, Claire L.,Mikusova, Alexandra,Lichvar, Peter,Hyatt, Neil C. Korean Radioactive Waste Society 2021 방사성폐기물학회지 Vol.19 No.3
Legacy waste from the decommissioned A-1 nuclear power plant in the Slovak Republic is scheduled for immobilisation within a tailored alkali borosilicate glass formulation, as part of ongoing site cleanup. The aqueous durability and characterisation of a simulant glass wasteform for Chrompik III legacy waste, was investigated, including dissolution experiments up to 112 days (90℃, ASTM Type 1 water). The wasteform was an amorphous, light green glassy product, with no observed phase separation or crystalline inclusions. Aqueous leach testing revealed a suitably durable product over the timescale investigated, comparing positively to other simulant nuclear waste glasses and vitreous products tested under similar conditions. Iron and titanium rich precipitates were observed to form at the surface of monolithic samples during leaching, with the formation of an alkali deficient alteration layer behind these at later ages. Overall this glass appears to perform well, and in line with expectations for this chemistry, although longer-term testing would be required to predict overall durability. This work will contribute to developing confidence in the disposability of vitrified Chrompik legacy wastes.