Discovery-of-novel-SecA-inhibitors.pdf

Bioorganic Medicinal Chemistry Letters 21 (2011) 4183–4188Contents lists available at ScienceDirect Bioorganic Medicinal Chemistry Letters journal homepage: www.elsevier .com/ locate/bmclDiscovery of novel SecA inhibitors of Candidatus Liberibacter asiaticus by structure based design Nagaraju Akula a, Hong Zheng b, Frank Q. Han b, Nian Wang a,? aCitrus Research Education Center, Department of Microbiology and Cell Science, University of Florida, 700 Experiment Station Rd., Lake Alfred, FL 33850, USA b Structure Based Design, Inc., 6048 Cornerstone Court West, Suite D, San Diego, CA 92121, USA a r t i c l e i n f o a b s t r a c tArticle history: Received 9 April 2011 Revised 22 May 2011 Accepted 23 May 2011 Available online 30 May 2011 Keywords: SecA Virtual screening Structure Molecular docking Inhibitors0960-894X/$ - see front matter  2011 Elsevier Ltd. A doi:10.1016/j.bmcl.2011.05.086 ? Corresponding author. Tel.: +1 863 956 1151; fax E-mail address: nianwang@ (N. Wang).Candidatus Liberibacter asiaticus is the causal agent of Huanglongbing (HLB) disease of citrus. Current management practices have not been able to control HLB and stop the spread of HLB. The current study is focused on screening small molecule inhibitors against SecA protein of Ca. L. asiaticus. Homology mod- eling, structure based virtual screening and molecular docking methods have been used to find the novel inhibitory compounds against SecA activity at ATP binding region. At 20 lm 17 compounds showed 50% inhibition and four compounds had more than 65% inhibition. The most active compound has IC50 value of 2.5 lM. The differences between the activities of the compounds are explained by their inter-molec- ular interactions at ATP binding site.  2011 Elsevier Ltd. All rights reserved.Huanglongbing (HLB) is the most devastating disease of citrus. HLB has seriously affected citrus production in a number of coun- tries in Asia, Africa, the Indian subcontinent, the Arabian Peninsula, and a numbe