title: Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia.
abstract: Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37 RV . Antitubercular (anti-TB) bioassay-guided isolation of the CHCl3 extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti-TB 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37 RV . Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 and 79.2 μm in MABA assay, respectively, and 91.7 and 168.3 μm in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti-TB activity than its synthetic precursor (2) with MIC values at 42.0 μm in MABA assay and 100.2 μm in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti-TB agents. The distinct structure-activity correlations of the parent compound were elucidated based on these derivatives.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|HKBU Institute of Research and Continuing Education, Shenzhen, 518057, China.
authors.forename: Yi-Fu
authors.initials: YF
authors.lastname: Guan
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Department of Pharmacy, School of Medicine, Key Laboratory of Novel Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Song
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Luo
authors.affiliation: Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL, 60612, USA.
authors.forename: Bao-Jie
authors.initials: BJ
authors.lastname: Wang
authors.affiliation: Institute of Marine Biochemistry of the Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet Road, Cau Giay, Hanoi, Vietnam.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Hung
authors.affiliation: Cuc Phuong National Park, Nho Quan District, Ninh Binh Province, Vietnam.
authors.forename: Nguyen M
authors.initials: NM
authors.lastname: Cuong
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL, 60612, USA.
authors.forename: Djaja Doel
authors.initials: DD
authors.lastname: Soejarto
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL, 60612, USA.
authors.forename: Harry H S
authors.initials: HH
authors.lastname: Fong
authors.affiliation: Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL, 60612, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Li
authors.affiliation: Department of Pharmacy, School of Medicine, Key Laboratory of Novel Health Care Products, Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Zhen-Dan
authors.initials: ZD
authors.lastname: He
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Zhang
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D031644:Ardisia / Q000737:chemistry*; D001681:Biological Assay; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000494:pharmacology*; D012118:Resorcinols / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000995:Antitubercular Agents; D010936:Plant Extracts; D012118:Resorcinols
keywords: Ardisia gigantifolia; Mycobacterium tuberculosis H37RV; anti-TB activity; isolation and structure identification; resorcinols; structural modification