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Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/3058
Title: 1,4-Benzoquinone antimicrobial agents against Staphylococcus aureus and Mycobacterium tuberculosis derived from scorpion venom
Authors: Carcamo-Noriega E.N.
Sathyamoorthi S.
Banerjee S.
Gnanamani E.
Mendoza-Trujillo M.
Mata-Espinosa D.
Hernández-Pando R.
Veytia-Bucheli J.I.
Possani L.D.
Zare R.N.
Published in: Proceedings of the National Academy of Sciences of the United States of America
Abstract: Two 1,4-benzoquinone derivatives, found in the venom of the scorpion Diplocentrus melici following exposure to air, have been isolated, characterized, synthesized, and assessed for antimicrobial activities. Initially a white, viscous liquid, the extracted venom colors within minutes under ambient conditions. From this colored mixture, two compounds, one red, the other blue, were isolated and purified using chromatography. After a variety of NMR and mass spectrometry experiments, the red compound was determined to be 3,5- dimethoxy-2-(methylthio)cyclohexa-2,5-diene-1,4-dione, and the blue compound was determined to be 5-methoxy-2,3- bis(methylthio) cyclohexa-2,5-diene-1,4-dione. Because extremely small amounts of these compounds were isolated from the scorpion venom, we developed laboratory syntheses from commercially available precursors, allowing us to produce sufficient quantities for crystallization and biological assays. The red benzoquinone is effective against Staphylococcus aureus [minimum inhibitory concentration (MIC) = 4 ?g/mL], while the blue benzoquinone is active against Mycobacterium tuberculosis (MIC = 4 ?g/mL) and even against a multidrug-resistant (MDR) strain with nearly equal effectiveness. The bactericidal effects of both benzoquinones show comparable activity to commercially available antibiotics used against these pathogens and were cytotoxic to neoplastic cell lines, suggesting their potential as lead compounds for the development of novel antimicrobial and anticancer drugs. Importantly, the blue benzoquinone was also effective in vivo with mouse models of MDR tuberculosis infection. After treatment for 2 mo, four mice with late-stage active MDR tuberculosis had a significant decrease in pulmonary bacillary loads and tissue damage. Healthy mice served as negative controls and tolerated treatment well, without adverse side effects. © 2019 National Academy of Sciences. All rights reserved.
Citation: Proceedings of the National Academy of Sciences of the United States of America (2019), 116(26): 12642-12647
URI: https://doi.org/10.1073/pnas.1812334116
http://repository.iitr.ac.in/handle/123456789/3058
Issue Date: 2019
Publisher: National Academy of Sciences
Keywords: Antimicrobial activity
Benzoquinones
Mycobacterium tuberculosis
Scorpion venom
Staphylococcus aureus
ISSN: 278424
Author Scopus IDs: 57103835900
26645209200
37080201400
35319775800
57209568336
56013578900
7007157049
57203371241
56013752900
35355951800
Author Affiliations: Carcamo-Noriega, E.N., Department of Molecular Medicine and Bioprocesses, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Morelos, 62210, Mexico
Sathyamoorthi, S., Department of Chemistry, Stanford University, Stanford, CA 94305, United States
Banerjee, S., Department of Chemistry, Stanford University, Stanford, CA 94305, United States, Department of Chemistry, Indian Institute of Science Education and Research Tirupati, Tirupati, 517507, India
Gnanamani, E., Department of Chemistry, Stanford University, Stanford, CA 94305, United States
Mendoza-Trujillo, M., Section of Experimental Pathology, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,”, Mexico City, 14080, Mexico
Mata-Espinosa, D., Section of Experimental Pathology, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,”, Mexico City, 14080, Mexico
Hernández-Pando, R., Section of Experimental Pathology, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,”, Mexico City, 14080, Mexico
Veytia-Bucheli, J.I., Department of Molecular Medicine and Bioprocesses, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Morelos, 62210, Mexico
Possani, L.D., Department of Molecular Medicine and Bioprocesses, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Morelos, 62210, Mexico
Zare, R.N., Department of Chemistry, Stanford University, Stanford, CA 94305, United States
Funding Details: ACKNOWLEDGMENTS. We acknowledge the support and help received from Diego Martínez Otero for the X-ray diffraction study, Stephen R. Lynch for the NMR study, and J. C. Leon-Contreras for the ultrastructural study. S.B. thanks Science and Engineering Research Board, Department of Science and Technology, India, for providing a Ramanujan Fellowship Research Grant. This work was supported by the Air Force Office of Scientific Research through Basic Research Initiative Grant AFOSR FA9550-16-1-0113.
Corresponding Author: Possani, L.D.; Department of Molecular Medicine and Bioprocesses, Instituto de Biotecnologia, Universidad Nacional Autonoma de MexicoMexico; email: possani@ibt.unam.mx
Appears in Collections:Journal Publications [CY]

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