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Recent years have brought in an increased interest to develop improved polymyxins. The currently used polymyxins, i.e. polymyxin B and colistin (polymyxin E) are pentacationic lipopeptides that possess a cyclic heptapeptide part with three positive charges, a linear “panhandle” part with two positive charges, and a fatty acyl tail. Unfortunately, their clinical use is shadowed by their notable nephrotoxicity...
The emergence of very multiresistant Gram-negative bacterial strains has reinstated polymyxins (polymyxin B, colistin), pentacationic lipopeptides, in the therapy, in spite of their nephrotoxicity. Extensive tubular reabsorption concentrates polymyxin in proximal tubular cells. The novel polymyxin derivatives NAB739, NAB7061 and NAB741 have their cyclic part identical to that of polymyxin B, but their...
Polymyxin B and colistin are pentacationic lipopeptides that possess a cyclic heptapeptide portion, a linear tripeptide portion, and a fatty acyl tail. They are used, in spite of nephrotoxicity, to treat infections caused by extremely multiresistant Gram-negative bacteria. We have recently developed novel derivatives, that carry three cationic charges only. Some of them, including NAB739, are directly...
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