Synthesis and evaluation of functionalized benzoboroxoles as potential anti-tuberculosis agents

Mohammad A Alam; Kriti Arora; Shirisha Gurrapu; Sravan K Jonnalagadda; Grady L Nelson; Paul Kiprof; Subash C Jonnalagadda; Venkatram R Mereddy

doi:10.1016/j.tet.2016.03.038

Synthesis and evaluation of functionalized benzoboroxoles as potential anti-tuberculosis agents

Tetrahedron. 2016 Jun 30;72(26):3795-3801. doi: 10.1016/j.tet.2016.03.038. Epub 2016 Mar 17.

Authors

Mohammad A Alam¹, Kriti Arora², Shirisha Gurrapu³, Sravan K Jonnalagadda³, Grady L Nelson³, Paul Kiprof⁴, Subash C Jonnalagadda⁵, Venkatram R Mereddy⁶

Affiliations

¹ Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA.
² Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
³ Integrated Biosciences Graduate Program, University of Minnesota, MN 55812, USA.
⁴ Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN 55812, USA.
⁵ Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA; Department of Biomedical and Translational Sciences, Rowan University, Glassboro, NJ 08028, USA.
⁶ Integrated Biosciences Graduate Program, University of Minnesota, MN 55812, USA; Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN 55812, USA; Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, MN 55812, USA.

Abstract

Several derivatives of aminobenzoboroxole have been prepared starting from 2-boronobenzaldehyde. All of these derivatives have been evaluated for their anti-mycobacterial activity on Mycobacterium smegmatis and cytotoxicity on breast cancer cell line MCF7. Based on these studies, all the tested molecules have been found to be generally non-toxic and benzoboroxoles with unsubstituted (primary) amines have been found to exhibit good anti-mycobacterial activity. Some of the key compounds have been evaluated for their anti-tubercular activity on Mycobacterium tuberculosis H37Rv using 7H9 and GAST media. 7-Bromo-6-aminobenzoboroxole 4 has been identified as the lead candidate compound for further development.

Keywords: Benzoxaboroles; aminobenzoxaborole; anti-tuberculosis agents; bromoaminobenzoxaborole; nitrobenzoxaborole.

Abstract

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