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Synthesis and antimycobacterial activity of novel camphane-based agents
Affiliation:1. Faculty of Pharmacy, Medical University of Sofia, Str. Dunav 2, Sofia 1000, Bulgaria;2. Institute of Organic Chemistry, Bulgarian Academy of Sciences, Acad. Bonchev 9, Sofia 1113, Bulgaria;3. Institute of Microbiology, Bulgarian Academy of Sciences, Akad. Bonchev 26, Sofia 1113, Bulgaria;1. Laboratorio de Bajas Temperaturas, Departamento de Física de la Materia Condensada, Instituto de Ciencia de Materiales Nicolás Cabrera, Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid, Spain;2. Unidad Asociada de Bajas Temperaturas y Altos Campos Magnéticos, UAM, CSIC, Cantoblanco, E-28049 Madrid, Spain;3. Laboratorio de Microscopías Avanzadas (LMA) – Instituto de Nanociencia de Aragón (INA), Universidad de Zaragoza, Zaragoza 50009, Spain;4. Departamento de Física de la Materia Condensada, Universidad de Zaragoza, 50009 Zaragoza, Spain;5. Instituto de Ciencia de Materiales de Aragón (ICMA), Universidad de Zaragoza-CSIC, Facultad de Ciencias, Zaragoza 50009, Spain;6. Department of Physics, Indian Institute of Technology, Kanpur 208016, U.P., India;1. Department of Biological Sciences, Konkuk University, Seoul 05029, Republic of Korea;2. Cancer and Metabolism Institute, Konkuk University, Seoul 05029, Republic of Korea;3. Department of Applied Chemistry, Dongduk Women''s University, Seoul 02748, Republic of Korea;4. Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 05029, Republic of Korea;1. University of Chemical Technology and Metallurgy, Department of Organic Chemistry, 8 St. “Kliment Ohridski” Blvd., 1756 Sofia, Bulgaria;2. Institute of Organic Chemistry with Centre of Phytochemistry, Laboratory of Chemistry and Biophysics of Proteins and Enzymes, Bulgarian Academy of Science, 9 “Acad. G. Bonchev” Blvd., Sofia 1113, Bulgaria;3. Institute of Optical Materials and Technologies “Acad. Jordan Malinovski”, Department of “Nanostructured Materials and Technology”, Bulgarian Academy of Science, 109 “Acad. G. Bonchev” Blvd., 1113 Sofia, Bulgaria;1. Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan;2. Core Research for Evolutional Science and Technology (CREST), Science and Technology (JST) Agency, K’s Gobancho, 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan;3. College of Optical Sciences, The University of Arizona, 1630 East University Boulevard, Tucson, Arizona 85721, USA
Abstract:A series of six new amidoalcohols was designed and synthesized on the base of the camphor scaffold. Natural amino acids were transformed into their α-hydroxy analogues with retention of configuration, and attached to isobornylamine. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. Some of the new compounds show 25 times higher activity than the classical anti-TB drug ethambutol. The activity shifts from micromolar to nanomolar inhibitory concentrations depending on the α-hydroxy acid moiety. Two of the most potent compounds exert low level of cytotoxic activity. These camphane-based amido-alcohols present promising potential lead compounds for further elaboration of antimycobacterial agents.
Keywords:Camphane  Isobornylamine  α-Hydroxy acids  Antimycobacterial activity
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