Chemical Constituents and Biological Activities of Selected Artocarpus Spp.

• Main Author: Mohd. Hashim, Najihah
• Format: Thesis
• Language: English; English
• Published: 2011
• Online Access: http://psasir.upm.edu.my/id/eprint/19602/1/FS_2011%2014.pdf; http://psasir.upm.edu.my/id/eprint/19602/

Thirty three extracts of stem barks of eleven Artocarpus species from Moraceae family were preliminary screened in vitro for their biological activities. Four potential plants, Artocarpus kemando, A. melinoxylus, A. obtusus and A. rigidus had been selected based on the preliminary bioassay screenings results for further phytochemical and biological studies. The species were subjected for detail isolation work which involves extraction and isolation of compounds by using several chromatographic techniques. The structural elucidations of the isolated compounds were carried out using spectroscopic methods such as UV, IR, NMR, MS and also by comparison with the literature data. These techniques have led to the isolation and identification of several compounds of different classes, the flavonoid derivatives, a coumarin, a dipeptide and a sterol. The crude extracts and some of the isolated compounds were screened for cytotoxic, antioxidant, antimicrobial and tyrosinase inhibitory activity using MTT (Microculture Tetrazolium Salt), DPPH (1,1-diphenyl-2-picrylhydrazyl), disc diffusion and dopachrome methods, respectively. The cell lines used in the cytotoxic assay were human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), human hepatocarcinoma (HepG2), human colon cancer (HT29), human cervical cancer (HeLa), human estrogen receptor (ER+) positive breast cancer (MCF7), human estrogen receptor (ER-) negative (MDA-MB 231), peripheral blood mononuclear cells (PBMC) and human non-tumorigenic breast cell line (MCF10A). The antimicrobial activity was tested against several selected pathogenic microbes, Bacillus subtilis (clinically isolated strain), Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Methicillin resistant Staphylococcus aureus (MRSA) (ATCC 33591), Micrococcus luteus ATCC 10240, Pseudomonas aeruginosa (JCM 2412), Salmonella typhimurium S865B (IMR culture), Staphylococcus aureus ATCC 6538, Aspergillus niger ATCC 16404, Candida albicans ATCC 1023 and Saccharomyces cerevisiae S617 (IMR culture). Detail study on A. obtusus has led to the isolation of three new flavonoid derivatives, yranocycloartobiloxanthone A (112),dihydroartoindonesianin C (113) and pyranocycloartobiloxanthone B (114), and a sterol, β- itosterol (115). Phytochemical work of A. rigidus yielded pyranocycloartobiloxanthone A (112), artoindonesianin C (34) and β-sitosterol (115). However, the isolation work on A. melinoxylus has also afforded a similar compound as previously isolated from the first two plants, pyranocycloartobiloxanthone A (112) and a known xanthone, cycloartobiloxanthone (24). Similar work on A. kemando has yielded four interesting compounds, cycloartobiloxanthone (24), dihydroartoindonesianin C (113), 6, 7–dimethoxycoumarin (116) and aurantiamide benzoate (117). The coumarin and the dipeptide are new isolated compounds from the Artocarpus species. Only three compounds, namely, pyranocycloartobiloxanthone A (112), dihydroartoindonesianin C (113) and pyranocycloartobiloxanthone B (114) were subjected to bioassay screenings due to inadequate amount of isolated compounds. The compounds exhibited various interesting activities towards the assays. However, pyranocycloartobiloxanthone A (112) is the most potential bioactive compound towards the cytotoxic, DPPH free radical scavenging, tyrosinase inhibitory and a broad spectrum of antimicrobial activity compared to the other two compounds. The study on antiproliferative activity using ELISA BrdU assay against HL60 and MCF7 cell lines, showed that pyranocycloartobiloxanthone A (112) was able to impair the DNA synthesis and cell proliferation. The cytotoxic effect of pyranocycloartobiloxanthone A (112) on the HL60 and MCF7 cell lines was studied based on the morphological manner for over 72 hours. The microscopic observations, including inverted microscopy of live cultures and fluorescent microscopy of acridine orange-propidium iodide stained cultures, showed that both necrotic and apoptotic death occurred in pyranocycloartobiloxanthone A (112) treated cell populations at IC50 concentrations.