中文版 | English
Title

Antimycobacterial Compound of Cynoglossum lanceolatum Forsk.: Bioassay Guided Isolation, Molecular Docking, Synthesis of Analogs, and a Plausible Mechanism of Action

Author
Corresponding AuthorYang, Zai-Chang
Publication Years
2023-01-12
DOI
Source Title
ISSN
1612-1872
EISSN
1612-1880
Abstract

Tuberculosis (TB) remains a major threat to human health. Due to the prevalence of drug-resistant Mycobacterium tuberculosis (Mtb), it is urgent to discover drugs with new mechanisms of action (MOA) to ensure effectiveness against strains that are resistant to existing TB drugs. Cynoglossum lanceolatum Forsk was used to treat TB in Traditional Chinese Medicine. In this article, shikonin, the anti-Mtb active component, was obtained from the whole herb extract of C. lanceolatum by bioassay-guided isolation. Using the microplate alamar blue assay (MABA), the minimum inhibitory concentration (MIC) of shikonin against Mtb was determined to be 128 mu g/mL. In order to obtain a more efficient anti-Mtb molecule, (E)-1-(6-bromo-2,3-dihydrochromen-4-ylidene)thiosemicarbazide was synthesized based on the scaffold of shikonin, which exhibited potent activity against Mtb (MIC=4 mu g/mL). These results highlight that both naphthalene-1,4-dione and chroman-4-one are pharmacophores with activities against Mtb. To investigate a plausible mechanism of action, the molecular docking was firstly performed against catalase-peroxidase enzyme (KatG) of Mtb using AutoDock 4 software. The results demonstrated that both shikonin and (E)-1-(6-bromo-2,3-dihydrochromen-4-ylidene)thiosemicarbazide could bind to the active site of Mtb KatG. KatG enzyme activity and intracellular reactive oxygen species (ROS) levels in Mtb cells were then measured by ultraviolet spectrophotometric method and fluorescence microplate reader assay, respectively. The experiments confirmed that above compounds could inhibit the catalytic activity of Mtb KatG, and cause the ROS accumulation in Mtb cells. Therefore, inhibition of KatG may be a novel mechanism of action for these two compounds to fight against Mtb.

Keywords
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
Corresponding
Funding Project
National Natural Science Foundation of China[
WOS Research Area
Biochemistry & Molecular Biology ; Chemistry
WOS Subject
Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS Accession No
WOS:000913284800001
Publisher
ESI Research Field
ENVIRONMENT/ECOLOGY
Data Source
Web of Science
Citation statistics
Cited Times [WOS]:0
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/425183
DepartmentSUSTech-Peking University National Institute of Plants and Food
生命科学学院
生命科学学院_生物系
Affiliation
1.Guizhou Univ, Coll Pharm, Guiyang 550025, Peoples R China
2.Southern Univ Sci & Technol, Key Lab Mol Design Plant Cell Factory, Inst Plant & Food Sci, Dept Biol,Guangdong Higher Educ Inst, Shenzhen 518055, Peoples R China
Corresponding Author AffilicationSUSTech-Peking University National Institute of Plants and Food;  Department of Biology;  School of Life Sciences
Recommended Citation
GB/T 7714
Zhao, Xin,Wang, Lei,Xia, Meng-Yu,et al. Antimycobacterial Compound of Cynoglossum lanceolatum Forsk.: Bioassay Guided Isolation, Molecular Docking, Synthesis of Analogs, and a Plausible Mechanism of Action[J]. CHEMISTRY & BIODIVERSITY,2023.
APA
Zhao, Xin,Wang, Lei,Xia, Meng-Yu,&Yang, Zai-Chang.(2023).Antimycobacterial Compound of Cynoglossum lanceolatum Forsk.: Bioassay Guided Isolation, Molecular Docking, Synthesis of Analogs, and a Plausible Mechanism of Action.CHEMISTRY & BIODIVERSITY.
MLA
Zhao, Xin,et al."Antimycobacterial Compound of Cynoglossum lanceolatum Forsk.: Bioassay Guided Isolation, Molecular Docking, Synthesis of Analogs, and a Plausible Mechanism of Action".CHEMISTRY & BIODIVERSITY (2023).
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