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Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp.

Multi- or extensive TB drug resistance, co-infection of HIV/TB and the burdensome persistent infection have placed tuberculosis (TB) as a global emergence that causes 2 million deaths annually. During persistency, Mycobacterium tuberculosis utilizes the glyoxylate pathway to survive, thus making pat...

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Main Author: Khoo, Yau Liang
Format: Thesis
Language:English
English
Published: 2013
Subjects:
QK710-899 Plant physiology
Online Access:https://eprints.ums.edu.my/id/eprint/41628/1/24%20pages.pdf
https://eprints.ums.edu.my/id/eprint/41628/2/FULLTEXT.pdf
https://eprints.ums.edu.my/id/eprint/41628/
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spelling my.ums.eprints.416282024-11-26T05:30:14Z https://eprints.ums.edu.my/id/eprint/41628/ Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp. Khoo, Yau Liang QK710-899 Plant physiology Multi- or extensive TB drug resistance, co-infection of HIV/TB and the burdensome persistent infection have placed tuberculosis (TB) as a global emergence that causes 2 million deaths annually. During persistency, Mycobacterium tuberculosis utilizes the glyoxylate pathway to survive, thus making pathway enzymes such as isocitrate lyase (ICL) and malate synthase (MLS) valuable drug targets to improve persistent-TB control. The main objective of this study was to identify potential persistent inhibitor(s) targeting the specific enzyme (MLS) in the acetate growth of Mycobacterium sp. A total of 117 extracts prepared from the 44 local plants and 60 soil actinomycetes were screened against MLS using the non-pathogenic form of mycobacteria (M. smegmatis mc2155, H8000) in agar diffusion assay. The potential crude extracts were further analyzed using modified Resazurin Microtiter Assay (REMA), MLS enzymatic assay and Tetrazolium Microplate Assay (TEMA). Among the extracts tested, Hopea pentanarvia (plant) and H7763 (actinomycete) gave the most potent growth inhibition activity on M. smegmatis in REMA. The H7763 extract produced most promising MLS growth inhibitory effect and the Hopea pentanarvia showed potential anti-mycobacterium activity against the pathogenic strain, M. tuberculosis H37Rv. Following this, both potential extracts were selected for bioassay-guided fractionation, and yielded a number of bioactive compounds which were characterized by spectroscopic methods [UV, IR, Mass Spectrometry (MS), 1D- and HMBC NMR]. Hopea pentanarvia yielded a known resveratrol derivative which was finally proposed as cis -Upunaphenol K. H7763 gave a known nucleoside compound named guanine 7-N-oxide. In addition to these structural studies, a minimum inhibition concentration (MIC) agar diffusion assay was performed using the nucleoside and resveratrol derivative against M. smegmatis with 3-nitropropionate (a known ICL prototypic inhibitor) as positive control. This nucleoside (8.1 ± 2.3 μg/disc) gave the lowest MIC value compared to the resveratrol derivative (70.0 ± 14.1 μg/disc) and the known inhibitor (37.5 ± 3.5 μg/disc). The nucleoside may require further research on toxicity before use in the development of antitubercular drug against M. tuberculosis . 2013 Thesis NonPeerReviewed text en https://eprints.ums.edu.my/id/eprint/41628/1/24%20pages.pdf text en https://eprints.ums.edu.my/id/eprint/41628/2/FULLTEXT.pdf Khoo, Yau Liang (2013) Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp. Masters thesis, Universiti Malaysia Sabah.
institution Universiti Malaysia Sabah
building UMS Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Sabah
content_source UMS Institutional Repository
url_provider http://eprints.ums.edu.my/
language English
English
topic QK710-899 Plant physiology
spellingShingle QK710-899 Plant physiology
Khoo, Yau Liang
Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp.
description Multi- or extensive TB drug resistance, co-infection of HIV/TB and the burdensome persistent infection have placed tuberculosis (TB) as a global emergence that causes 2 million deaths annually. During persistency, Mycobacterium tuberculosis utilizes the glyoxylate pathway to survive, thus making pathway enzymes such as isocitrate lyase (ICL) and malate synthase (MLS) valuable drug targets to improve persistent-TB control. The main objective of this study was to identify potential persistent inhibitor(s) targeting the specific enzyme (MLS) in the acetate growth of Mycobacterium sp. A total of 117 extracts prepared from the 44 local plants and 60 soil actinomycetes were screened against MLS using the non-pathogenic form of mycobacteria (M. smegmatis mc2155, H8000) in agar diffusion assay. The potential crude extracts were further analyzed using modified Resazurin Microtiter Assay (REMA), MLS enzymatic assay and Tetrazolium Microplate Assay (TEMA). Among the extracts tested, Hopea pentanarvia (plant) and H7763 (actinomycete) gave the most potent growth inhibition activity on M. smegmatis in REMA. The H7763 extract produced most promising MLS growth inhibitory effect and the Hopea pentanarvia showed potential anti-mycobacterium activity against the pathogenic strain, M. tuberculosis H37Rv. Following this, both potential extracts were selected for bioassay-guided fractionation, and yielded a number of bioactive compounds which were characterized by spectroscopic methods [UV, IR, Mass Spectrometry (MS), 1D- and HMBC NMR]. Hopea pentanarvia yielded a known resveratrol derivative which was finally proposed as cis -Upunaphenol K. H7763 gave a known nucleoside compound named guanine 7-N-oxide. In addition to these structural studies, a minimum inhibition concentration (MIC) agar diffusion assay was performed using the nucleoside and resveratrol derivative against M. smegmatis with 3-nitropropionate (a known ICL prototypic inhibitor) as positive control. This nucleoside (8.1 ± 2.3 μg/disc) gave the lowest MIC value compared to the resveratrol derivative (70.0 ± 14.1 μg/disc) and the known inhibitor (37.5 ± 3.5 μg/disc). The nucleoside may require further research on toxicity before use in the development of antitubercular drug against M. tuberculosis .
format Thesis
author Khoo, Yau Liang
author_facet Khoo, Yau Liang
author_sort Khoo, Yau Liang
title Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp.
title_short Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp.
title_full Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp.
title_fullStr Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp.
title_full_unstemmed Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp.
title_sort potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of mycobacterium sp.
publishDate 2013
url https://eprints.ums.edu.my/id/eprint/41628/1/24%20pages.pdf
https://eprints.ums.edu.my/id/eprint/41628/2/FULLTEXT.pdf
https://eprints.ums.edu.my/id/eprint/41628/
_version_ 1817843826749865984
score 13.223943

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