Talukdar, ArindamBreen, MeganBacher, AdelbertIllarionov, BorisFischer, MarkusGeorg, Gunda I.Ye, Qi-ZhuangCushman, Mark2017-04-122017-04-122009Talukdar, A., Breen, M., Bacher, A., Illarionov, B., Fischer, M., Georg, G., … Cushman, M. (2009). Discovery and Development of a Small Molecule Library with Lumazine Synthase Inhibitory Activity. The Journal of Organic Chemistry, 74(15), 5123–5134. http://doi.org/10.1021/jo900238qhttps://hdl.handle.net/1808/23638(E)-5-Nitro-6-(2-hydroxystyryl)pyrimidine-2,4(1H,3H)-dione (9) was identified as a novel inhibitor of Schizosaccharomyces pombe lumazine synthase by high-throughput screening of a 100,000 compound library. The Ki of 9 vs. Mycobacterium tuberculosis lumazine synthase was 95 μM. Compound 9 is a structural analog of the lumazine synthase substrate, 5-amino-6-(D-ribitylamino)-2,4-(1H,3H)pyrimidinedione (1). This indicates that the ribitylamino side chain of the substrate is not essential for binding to the enzyme. Optimization of the enzyme inhibitory activity through systematic structure modification of the lead compound 9 led to (E)-5-nitro-6-(4-nitrostyryl)pyrimidine-2,4(1H,3H)-dione (26), which has a Ki of 3.7 μM vs. M. tuberculosis lumazine synthase.Per SHERPA/RoMEO 4/12/2017: Author's Pre-print: grey tick subject to Restrictions below, author can archive pre-print (ie pre-refereeing) Restrictions: Must obtain written permission from Editor Must not violate ACS ethical Guidelines Author's Post-print: grey tick subject to Restrictions below, author can archive post-print (ie final draft post-refereeing) Restrictions: If mandated by funding agency or employer/ institution If mandated to deposit before 12 months, must obtain waiver from Institution/Funding agency or use AuthorChoice 12 months embargo Publisher's Version/PDF: cross author cannot archive publisher's version/PDF General Conditions: On author's personal website, pre-print servers, institutional website, institutional repositories or subject repositories Non-Commercial Must be accompanied by set statement (see policy) Must link to publisher version Publisher's version/PDF cannot be usedArticle10.1021/jo900238qopenAccess