The ‘resistance bacteria era’ is intrinsically related to the hospital acquired infections (HAI). The most frequent HAI causal agent in USA is multidrug resistant Staphylococcus aureus (MRSA) a priority of the Center for Disease Control for development for development of new drug treatments. A HAI key treatment is the oto and nephrotoxic aminoglycosides. One strategy is to enhance the antibiotic activity of antibiotics by combination with NPs, e.g., amoxicillin and the beta–lactamase inhibitor clavulanate.
Solutions for this urgent worldwide need can derive from bioprospecting species, specially from biodiversity rich countries e.g., the Guatemalan rainforests. Bioprospecting studies are envisioned under a business framework that are economic, social and eco–sustainable in the long term.
The enhancement of the bactericidal activity of commercially available aminoglycosides (GEN, VAN) by polar extracts from three Guatemalan rain forest plants were evaluated: the cosmetic oil producer palm Attalea cohune (Ac and fraction Ac11k), the Catholic relic Bourreria huanita (Bh), and the food spice Dysphania ambrosioides (Da). The antibiotics’ minimal bactericidal concentration (MBC) against MRSA–USA–300: Ac11k was reduced to 1/16MBCGEN at 9.9 Ac11k mg/mL (synergistic effects), and to 1/2MBCVAN at 94 Ac11k mg/mL (additive effects), and to 1/4MBCGEN at 136 mg/mL ethanolic extract of Bh. The Da–ascaridol–less leaves’ extracts reduced Erwinia carotovora doubling time from 17 min to 12.5 min. hinting out that they may be potentially useful for the probiotics’ industry.
With an emphasis in natural products dereplication by chemoinformatics tools, the experimental data gathered (HR–MS, FTIR, 1H–NMR spectroscopies) and the computational–assisted structure elucidation scheme were applied to derive the proposed structure of a new chemical entity probably present in Ac11k sample, Corozine A: a non–basic alkaloid with several putative ring types: (Z)-4-ethyl-1,2,6,7- tetrahydro-6,9-(methanoazenometheno)pyrrolo[2,1-d][1,5]oxazonine. Two additional potential targets related to sugars metabolism were found with ligand similarity search engines.
Corozine A and the other extracts studied are of interest for further research to improve its commercial exploitation. The vision of new commercial products derived from A. cohune would require a pilot project that re–engineers the extraction of fatty acids, essential oil, and alkaloids from the same raw material.
|Advisor:||Aga, Diana S., Wood, Troy|
|Commitee:||Aga, Diana S., Benedict, Jason, Diver, Steven, Wood, Troy|
|School:||State University of New York at Buffalo|
|School Location:||United States -- New York|
|Source:||DAI-B 80/07(E), Dissertation Abstracts International|
|Subjects:||Agronomy, Microbiology, Biochemistry|
|Keywords:||Antimicrobial adjuvants, Bioprospecting, Chemoinformatics, Fractional inhibitory concentration index, Natural products, Plants of the rainforest|
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