Plant natural products have played a pivotal role in the discovery and development of many new drugs for the treatment of various infectious diseases and cancers. The present study was therefore aimed at isolation and identification of novel bioactive compounds from selected plants collected in Malaysia with anti-cancer activity. Plant crude extracts were obtained using solvent extraction methods, while various chromatographic and spectroscopic methods were employed for compound isolation and structure elucidation. Evaluation of pure compounds and crude extracts for anti-cancer activity involved the use of Neutral Red assay (NR), acradine orange – ethidium bromide (AO/EB) staining and cell cycle analysis. Phytochemical investigations of five Malaysian plants, namely, Ficus hispida, F. fistulosa, F. schwarzii, Artocarpus heterophyllus x integer and Macaranga hypoleuca, with the focus on alkaloids and flavonoids, have resulted in the isolation of a total of 24 compounds, of which six are new. The leaf and stem-bark extracts of Ficus hispida yielded two new alkaloids, hispidacine (1) and hispiloscine (2), and a known alkaloid, 13a(S)-(+)-deoxypergularinine (3). Hispidacine represents the first example of an 8,4'-oxyneolignan incorporated an unusual 2-hydroxyethylamine moiety, while hispiloscine represents the first naturally occurring phenanthroindolizidine alkaloid with acetoxy substitution. The leaf and bark extracts of Ficus fistulosa provided two new septicine alkaloids, fistulopsines A and B (4 and 5), together with four known phenanthroindolizidine alkaloids, 13a(R)-(–)-3,6-didemethylisotylocrebrine (6), 13a(S)-(+)-tylocrebrine (7), 13a(S)-(+)-tylophorine (8) and 13a(S)-(+)-septicine (9), and one known non-alkaloid (vomifoliol, 10). The leaves of Ficus schwarzii gave two novel tri-nor-sesquilignan alkaloids, schwarzinicines A and B (11 and 12). The bark of Artocarpus heterophyllus x integer yielded five known compounds, of which four are prenylated flavonoids, namely, cudraflavone C (13), artocarpetin A (14), cycloheterophyllin (15) and artonin J (16), and one natural xanthone, lichexanthone (17). The leaves of Macaranga hypoleuca provided seven known compounds, of which three are flavonoid glycosides, namely, quercetin-3-O--L-arabinopyranoside (18), quercetin-3-O--L-arabinofuranoside (19) and quercetin-3-O-β-D-galactoside (20), three are flavonoid aglycones, namely, quercetin (21), kaempherol (22), and 5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)chroman-4-one (23), and one sterol 3-epi-taraxerol (24). Preliminary screening by NR assay found that the crude extracts (except for Artocarpus heterophyllus x integer) showed growth inhibitory activities against human breast (MDA-MB-231 and MCF-7), lung (A549), and colon (HCT-116) cancer cell lines. Of the 24 pure compounds obtained, hispiloscine (2), fistulopsine A (4), fistulopsine B (5) and cudraflavone C (13) were found to show growth inhibitory activity against colon (HCT-116) and breast (MCF-7) cancer cells. Furthermore, 4 and 5 were found to dominantly arrest cells in G1 phase of the cell cycle without the induction of apoptosis. Cell cycle perturbation of these compounds was found to be reversible for HCT-116 cells at the onset of 72 hours. These results suggest that 4 and 5 have the potential to be further exploited for the development of new anti-cancer agents.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:734346 |
| Date | January 2016 |
| Creators | Yap, Veronica Alicia |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/30655/ |
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