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Comparative Study
. 2007 Dec 1;17(23):6651-5.
doi: 10.1016/j.bmcl.2007.09.010. Epub 2007 Sep 7.

N-Benzyl-3-sulfonamidopyrrolidines as novel inhibitors of cell division in E. coli

Shubhasish Mukherjee  1 , Carolyn A Robinson, Andrew G Howe, Tali Mazor, Peter A Wood, Sameer Urgaonkar, Alan M Hebert, Debabrata Raychaudhuri, Jared T Shaw
Affiliations
Comparative Study

N-Benzyl-3-sulfonamidopyrrolidines as novel inhibitors of cell division in E. coli

Shubhasish Mukherjee et al. Bioorg Med Chem Lett. .

Abstract

A new small molecule inhibitor of bacterial cell division has been discovered using a high-throughput screen in Escherichia coli. Although the lead screening hit (534F6) exhibited modest inhibition of the GTPase activity of FtsZ (20+/-5% at 100microM of compound), a primary target for bacterial cell division inhibitors, several analogs caused potent bacterial growth inhibition with negligible antagonism of FtsZ GTPase activity. A library of analogs has been prepared and several alkyne-tagged photoaffinity probes have been synthesized for use in experiments to elucidate the primary target of this compound.

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Figures

Figure 1
Figure 1
Lead compound (534F6) from phenotypic HTS for compounds that induce lethal filamentation in E. coli.
Figure 2
Figure 2
E. coli DRC39 treated for 15h with A) 5 μM 14 15.
Scheme 1
Scheme 1
Synthesis of the enantiomers of 534F6
Scheme 2
Scheme 2
Solid- and solution-phase synthesis of analogs of 534F6.
Scheme 3
Scheme 3
Synthesis of 19, a benzophenone derivative of 534F6.
Scheme 4
Scheme 4
Synthesis of 23a and 23b, alkyne-tagged derivatives of 5a.
Scheme 5
Scheme 5
Synthesis of 29, an alkyne-tagged and azide-appended derivative of 534F6.
See this image and copyright information in PMC

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