title: Thermal and Photoinduced Copper-Promoted C-Se Bond Formation: Synthesis of 2-Alkyl-1,2-benzisoselenazol-3(2H)-ones and Evaluation against Mycobacterium tuberculosis.
abstract: 2-Alkyl-1,2-benzisoselenazol-3(2H)-ones, represented by ebselen (1a), are being studied intensively for a range of medicinal applications. We describe both a new thermal and photoinduced copper-mediated cross-coupling between potassium selenocyanate (KSeCN) and N-substituted ortho-halobenzamides to form 2-alkyl-1,2-benzisoselenazol-3(2H)-ones containing a C-Se-N bond. The copper ligand (1,10-phenanthroline) facilitates C-Se bond formation during heating via a mechanism that likely involves atom transfer (AT), whereas, in the absence of ligand, photoinduced activation likely proceeds through a single electron transfer (SET) mechanism. A library of 15 2-alkyl-1,2-benzisoselenazol-3(2H)-ones was prepared. One member of the library was azide-containing derivative 1j that was competent to undergo a strain-promoted azide-alkyne cycloaddition. The library was evaluated for inhibition of Mycobacterium tuberculosis (Mtb) growth and Mtb Antigen 85C (Mtb Ag85C) activity. Compound 1f was most potent with a minimal inhibitory concentration (MIC) of 12.5 μg/mL and an Mtb Ag85C apparent IC50of 8.8 μM.
authors.affiliation: Department of Chemistry and Biochemistry, The University of Toledo , 2801 W. Bancroft Street, Toledo, Ohio 43606, United States.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Thanna
authors.affiliation: Department of Chemistry and Biochemistry, The University of Toledo , 2801 W. Bancroft Street, Toledo, Ohio 43606, United States.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Goins
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Knudson
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Slayden
authors.affiliation: Department of Chemistry and Biochemistry, The University of Toledo , 2801 W. Bancroft Street, Toledo, Ohio 43606, United States.
authors.forename: Donald R
authors.identifier: 0000-0003-2583-8849
authors.initials: DR
authors.lastname: Ronning
authors.affiliation: Department of Chemistry and Biochemistry, The University of Toledo , 2801 W. Bancroft Street, Toledo, Ohio 43606, United States.
authors.forename: Steven J
authors.identifier: 0000-0003-0082-3827
authors.initials: SJ
authors.lastname: Sucheck
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D002244:Carbon / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D055668:Photochemical Processes; D018036:Selenium Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D018036:Selenium Compounds; D002244:Carbon; D003300:Copper