Infectious diseases are the major cause of human death worldwide and the need for new generations of anti-infective agents to overcome the drug resistant urgently needs to be tackled. Plant natural products are potential sources of novel antimicrobial compounds. In this study, an investigation into the antimicrobial lead compounds from Michelia figo, Macleaya cordata and Ardisia gigantifolia in Lingnan region is presented. The prevention of dental diseases is targeted at the control of dental biofilm. Streptococcus mutans and S. sobrinus are the leading bacterial strains in the formation of dental biofilm. Extracts of Michellia figo and Macleaya cordata displayed antimicrobial potential in our screening assays. Bioassay-guided isolation of M. figo revealed the presence of artabotryside B and acteoside which were isolated for the first time from this plant. Moreover, chelerythrine and sanguinarine, the two alkaloids isolated from Macleaya cordata displayed the ability to prevent the formation of biofilms of S. mutans and S. sobrinus with the MIC50 values in the range of 18.5-34.0 μM. Anti-TB bioassay-guided isolation of the extract of Ardisia gigantifolia led to isolation of two 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two compounds. Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 μM and 79.2 μM in MABA assay, respectively, and 91.7 μM 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. Chelerythrine and sanguinarine are the representative and the major active constituents of M. cordata. Both compounds showed significant fungicidal effects in vitro and significant therapeutic effects on guinea pigs of dermatophytosis. Mechanism study for the antifungal efficacy showed that chelerythrine and sanguinarine were potent inhibitors of ergosterol bio-synthesis by reducing the amount of ergosterol without affecting the synthesis of 1,3-β-glucan. In summary, these results highlight the promising antimicrobial activity of chelerythrine, sanguinarine and alkylresorcinols from the medicinal plants in Lingnan region. The active compounds may be regarded as new hits for further study as novel classes of antimicrobial agents for the treatment of infectious diseases.
| Identifer | oai:union.ndltd.org:hkbu.edu.hk/oai:repository.hkbu.edu.hk:etd_oa-1347 |
| Date | 13 January 2017 |
| Creators | Song, Xun |
| Publisher | HKBU Institutional Repository |
| Source Sets | Hong Kong Baptist University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Open Access Theses and Dissertations |
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