Novel Inhibitors of E. coli RecA ATPase Activity

Jonathan Z Sexton*, 1, Tim J Wigle2, Qingping He1, Mark A Hughes1, Ginger R Smith1, Scott F Singleton2, Alfred L Williams1, Li-An Yeh1
1 Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, 27707, USA
2 UNC Eshelman School of Pharmacy, Division of Medicinal Chemistry and Natural Products, The University of North Carolina at Chapel Hill, CB #7568, Chapel Hill, North Carolina, 27599-7568, USA

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© Sexton et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the 1801 Fayetteville St, BRITE Rm 2015, North Carolina Central University, Durham, North Carolina 27707, USA; Tel: 919-530-6251; Fax: 919-530-6600; E-mail:


The bacterial RecA protein has been implicated as a bacterial drug target not as an antimicrobial target, but as an adjuvant target with the potential to suppress the mechanism by which bacteria gain drug resistance. In order to identify small molecules that inhibit RecA/ssDNA nucleoprotein filament formation, we have adapted the phosphomolybdate-blue ATPase assay for high throughput screening to determine RecA ATPase activity against a library of 33,600 compounds, which is a selected representation of diverse structure of 350,000. Four distinct chemotypes were represented among the 40 validated hits. SAR and further chemical synthesis is underway to optimize this set of inhibitors to be used as antimicrobial adjuvant agents.

Keywords: Antibiotic resistance, ATPase inhibition, high throughput screening, microbial drug resistance, RecA, SOS response.