Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia

Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37RV. 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‐(8...

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Published inChemical biology & drug design Vol. 88; no. 2; pp. 293 - 301
Main Authors Guan, Yi-Fu, Song, Xun, Qiu, Ming-Hua, Luo, Shi-Hong, Wang, Bao-Jie, Van Hung, Nguyen, Cuong, Nguyen M., Soejarto, Djaja Doel, Fong, Harry H.S., Franzblau, Scott G., Li, Sheng-Hong, He, Zhen-Dan, Zhang, Hong-Jie
Format Journal Article
LanguageEnglish
Published HOBOKEN Blackwell Publishing Ltd 01.08.2016
Wiley
Subjects
anti-TB activity
Antitubercular Agents - chemistry
Antitubercular Agents - isolation & purification
Antitubercular Agents - pharmacology
Ardisia
Ardisia - chemistry
Ardisia gigantifolia
Biochemistry & Molecular Biology
Biological Assay
Chemistry, Medicinal
isolation and structure identification
Life Sciences & Biomedicine
Magnetic Resonance Spectroscopy
Microbial Sensitivity Tests
Mycobacterium tuberculosis
Mycobacterium tuberculosis H37RV
Pharmacology & Pharmacy
Plant Extracts - pharmacology
resorcinols
Resorcinols - chemistry
Resorcinols - isolation & purification
Resorcinols - pharmacology
Science & Technology
Spectrometry, Mass, Electrospray Ionization
structural modification
MYCOBACTERIUM-TUBERCULOSIS
DRUG
anti-TB activity
resorcinols
ASSAY
NATURAL-PRODUCTS
isolation and structure identification
Ardisia gigantifolia
Mycobacterium tuberculosis H37RV
structural modification
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Summary:Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37RV. 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 H37RV. 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. We have identified two antitubercular (anti‐TB) 5‐alkylresorcinols, 5‐(8Z‐heptadecenyl) resorcinol (1) and 5‐(8Z‐pentadecenyl) resorcinol (2) through bioassay‐guided separation from the leaves and stems of the medicinal plant Ardisia gigantifolia, and further synthesized 15 derivatives (3‐17) based on these two natural products. These compounds were evaluated for their anti‐TB activity against Mycobacterium tuberculosis H37RV.
Bibliography:Shenzhen strategic emerging industry development project
ark:/67375/WNG-K01LR5ZK-2
Natural Science Foundation of China - No. 21402166
NIH - No. 3U01TW001015-10S1; No. 2U01TW001015-11A1
istex:08BA8F6BEB1BCC71285FB6054E43132A773E9ECF
Hong Kong Baptist University (HKBU) Interdisciplinary Research Matching Scheme - No. RC-IRMS/12-13/03
Figure S1. 1H NMR (400 MHz, CDCl3) spectrum of compound 3. Figure S2. 13C NMR (100 MHz, CDCl3) spectrum of compound 3. Figure S3. 1H NMR (400 MHz, CDCl3) spectrum of compound 4. Figure S4. 13C NMR (100 MHz, CDCl3) spectrum of compound 4. Figure S5. 1H NMR (400 MHz, CDCl3) spectrum of compound 5. Figure S6. 13C NMR (100 MHz, CDCl3) spectrum of compound 5. Figure S7. 1H NMR (400 MHz, CDCl3) spectrum of compound 6. Figure S8. 13C NMR (100 MHz, CDCl3) spectrum of compound 6. Figure S9. 1H NMR (400 MHz, CDCl3) spectrum of compound 7. Figure S10. 13C NMR (100 MHz, CDCl3) spectrum of compound 7. Figure S11. 1H NMR (400 MHz, CDCl3) spectrum of compound 8. Figure S12. 13C NMR (100 MHz, CDCl3) spectrum of compound 8. Figure S13. 1H NMR (400 MHz, CDCl3) spectrum of compound 9. Figure S14. 13C NMR (100 MHz, CDCl3) spectrum of compound 9. Figure S15. 1H NMR (400 MHz, CDCl3) spectrum of compound 10. Figure S16. 1H NMR (400 MHz, CDCl3) spectrum of compound 11. Figure S17. 13C NMR (100 MHz, CDCl3) spectrum of compound 11. Figure S18. 1H NMR (400 MHz, CDCl3) spectrum of compound 12. Figure S19. 1H NMR (400 MHz, CDCl3) spectrum of compound 13. Figure S20. 13C NMR (100 MHz, CDCl3) spectrum of compound 13. Figure S21. 1H NMR (400 MHz, CDCl3) spectrum of compound 14. Figure S22. 1H NMR (400 MHz, CDCl3) spectrum of compound 15. Figure S23. 1H NMR (400 MHz, CDCl3) spectrum of compound 16. Figure S24. 1H NMR (400 MHz, CDCl3) spectrum of compound 17. Figure S25. 13C NMR (100 MHz, CDCl3) spectrum of compound 17. Figure S26. HRTOFMS spectrum of compound 1. Figure S27. HRTOFMS spectrum of compound 2. Figure S28. HRTOFMS spectrum of compound 3. Figure S29. HRTOFMS spectrum of compound 4. Figure S30. HRTOFMS spectrum of compound 5. Figure S31. HRTOFMS spectrum of compound 6. Figure S32. HRTOFMS spectrum of compound 7. Figure S33. HRTOFMS spectrum of compound 8. Figure S34. HRTOFMS spectrum of compound 9. Figure S35. HRTOFMS spectrum of compound 10. Figure S36. HRTOFMS spectrum of compound 11. Figure S37. HRTOFMS spectrum of compound 12. Figure S38. HRTOFMS spectrum of compound 13. Figure S39. HRTOFMS spectrum of compound 15. Figure S40. HRTOFMS spectrum of compound 16.
Foreign Agricultural Service of the USDA - No. CXZZ20150601110000604;; No. ZDSYS201506031617582
ArticleID:CBDD12756
NIH RePORTER
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1747-0277
1747-0285
DOI:10.1111/cbdd.12756