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...

Full description

Saved in:

Bibliographic Details
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
Tags:	Add Tag No Tags, Be the first to tag this record!

id	my-ums-ep.41628
record_format	uketd_dc
spelling	my-ums-ep.416282024-11-26T05:30:14Z Potential persistent mycobacterium inhibitors from plants and actinomycetes trageting isocitrate lyase and malate synthase in the glyoxylate shunt of Mycobacterium sp. 2013 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 https://eprints.ums.edu.my/id/eprint/41628/ https://eprints.ums.edu.my/id/eprint/41628/1/24%20pages.pdf text en public https://eprints.ums.edu.my/id/eprint/41628/2/FULLTEXT.pdf text en validuser masters Universiti Malaysia Sabah Sekolah Sains dan Teknologi
institution	Universiti Malaysia Sabah
collection	UMS Institutional Repository
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
qualification_level	Master's degree
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.
granting_institution	Universiti Malaysia Sabah
granting_department	Sekolah Sains dan Teknologi
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
_version_	1818611420534669312

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

Similar Items