Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.667582
Title: Metabolomics and dereplication studies of endophytic metabolites from some Egyptian medicinal plants in the search for new potential anti-cancer and antimicrobial drugs
Author: Tawfike, Ahmed
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2015
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Abstract:
Endophytes are microbes that inhabit living, internal tissues of plants without causing any immediate, apparent negative effects. Endophytic fungi associated with medicinal plants represent a potential source of novel chemistry and biology. This study involved isolation of three endophytic fungal strains from two Egyptian medicinal plants, Terminalia laxiflora and Markhamia platicalyx. Identification of the strains has been achieved through molecular biological methods. Metabolomic profiling, using 2D-NMR and HR-ESIFTMS were done at different stages of the growth phase for both solid and liquid culture media. Dereplication studies were accomplished by utilizing the MZmine 2.10 software with aid of the AntiBase and DNP databases. The optimized method in terms of media, incubation time, and maximum production of bioactive compounds were taken into account for the scale-up. The chemometric analysis using SIMCA-P v13 software was accomplished to compare the active and inactive extracts and/or fractions in order to highlight the bioactive metabolites at earlier stages. The bioassay-guided fractionation was established using flash chromatography that employed BUCHI®, Biotage® and Reveleris® flash systems. The cytotoxicity of extracts, fractions and the isolated compounds was tested against both chronic myelogenous leukemia (K562) and prostate cancer (PC3) cell lines. The antimicrobial activity was investigated against Trypanosoma brucei and Mycobacterium marinum ATCCBAA 535. This work led to isolation of three new natural compounds and 34 known endophytic metabolites from Aspergillus aculeatus, A. flocculus and Curvularia sp. The isolated fungal compounds were elucidated using 1D and 2D-NMR experiments and HR-ESIFTMS with aid of DNP databases. Secalonic acids D, B, F and C from A. aculeatus; phomaligol A, p-hydroxybenzaldehyde, 4-hydroxyphenyl-methoxy-acetic acid, mellein derivatives like mellein, trans-4-hydroxymellein and 5-hydroxymellien and diorcinol from A. flocculus; dipeptide (N-acetyl-phenylalanine-L-phenylalanine) from Curvularia sp., were the most significant bioactive metabolites. Metabolomics has been shown to be a powerful facilitator in the discovery of natural products, which are considered an excellent source for novel leads, and even more, as a means to highlight novel targets.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.667582  DOI: Not available
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