Two new phloroglucinol derivatives, identified as anthuminoate (1) and anthuminone (2), were isolated from the ichthyotoxic ethyl acetate fraction of Syzygium polyanthum leaves. In addition, bioassay-guided fractionation followed by dereplication of the photocytotoxic fraction of this plant part has resulted in the identification of five known pheophorbides as the bioactive constituents. The compounds were identified as pheophorbide-a, methyl pheophorbide-a, methyl hydroxypheophorbide-a, pheophorbide-b and hydroxypheophorbide-b. Inhibition of cell viability shown by the compounds ranged from 83.3 to 86.1% at a test concentration of 5 microg/mL. This shows that Syzygium polyanthum leaves are a potential new source in the studies of photocytotoxicity for photodynamic therapy.
Phytoplankton growth (μ) and grazing loss (g) rates were measured monthly by the Landry-Hassett dilution method over a 2-year period at both estuarine (Klang) and coastal water (Port Dickson) systems along the Straits of Malacca. Chlorophyll a (Chl a) concentration ranged from 0.20 to 4.47 μg L(-1) at Klang except on two occasions when Chl a spiked above 10 μg L(-1). In contrast, Chl a concentrations were relatively stable at Port Dickson (0.14 to 2.76 μg L(-1)). From the rate measurements, μ was higher (t = 2.01, df = 43, p 0.80). g ranged from 0.30 to 1.50 and 0.21 to 1.51 day(-1) at Klang and Port Dickson, respectively. In this study, grazing loss was coupled to phytoplankton growth, and the ratio of g/μ or grazing pressure which estimates the proportion of primary production grazed was 50% at Klang and lower than at Port Dickson (68%; t = 2.213, df = 36, p
In our screening program for new photosensitizers from the Malaysian biodiversity, we found five pheophorbide-related compounds from the leaves and stems of Aglaonema simplex. Detailed spectroscopic analyses showed that compounds 1-3 and 5 are pheophorbide and hydroxy pheophorbide derivatives of chlorophyll a and b. Compound 4, identified as 15(1)-hydroxypurpurin-7-lactone ethyl methyl diester, was isolated for the first time from the Araceae family. An MTT-based short-term survival assay showed that all five compounds exhibit moderate-to-strong photocytotoxic activities towards human leukemia (HL60) and two oral squamous carcinoma cell lines (HSC-2 and HSC-3). Compounds 4 and 5 showed the strongest photocytotoxicities, with IC(50) values of 0.30-0.41 muM (Table 2). Compounds 1-3 with Et chains at C(17(3)) were less photocytotoxic than the parent pheophorbide a (5).
In our screening program for new photosensitizers from Malaysian biodiversity for photodynamic therapy (PDT) of cancer, MeOH extracts of ten terrestrial plants from Cameron Highlands in Pahang, Peninsular Malaysia, were tested. In a short-term 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, 20 μg/ml each of these extracts were incubated in a pro-myelocytic leukemia cell-line, HL60, with or without irradiation with 9.6 J/cm(2) of a broad spectrum light. Three samples, Labisia longistyla, Dichroa febrifuga, and Piper penangense, were photocytotoxic by having at least twofold lower cell viability when irradiated compared to the unirradiated assay. The extract of the leaves of Piper penangense, a shrub belonging to the family Piperaceae and widely distributed in the tropical and subtropical regions in the world, was subsequently subjected to bioassay-guided fractionation using standard chromatography methods. Eight derivatives of pheophorbide-a and -b were identified from the fractions that exhibited strong photocytotoxicity. By spectroscopic analysis, these compounds were identified as pheophorbide-a methyl ester (1), (R,S)-13(2) -hydroxypheophorbide-a methyl ester (2 and 3), pheophorbide-b methyl ester (4), 13(2) -hydroxypheophorbide-b methyl ester (5), 15(2) -hydroxylactone pheophorbide-a methyl ester (6), 15(2) -methoxylactone pheophorbide-a methyl ester (7), 15(2) -methoxylactone pheophorbide-b methyl ester (8).
In our screening for photosensitizers from natural resources, 15(1)-hydroxypurpurin-7-lactone ethyl methyl diester (compound 1) was isolated for the first time from an Araceae plant. To evaluate the efficacy of compound 1 as a photosensitizer for head and neck cancers, compound 1 was studied in reference to a known photosensitizer pheophorbide-a (Pha), in terms of photophysical properties, singlet oxygen generation and in in vitro experiments (intracellular uptake and phototoxicity assays) in two oral (HSC2 and HSC3) and two nasopharyngeal (HK1 and C666-1) cancer cell lines. In this study, compound 1 exhibited higher intracellular uptake over 24 h compared with Pha in both HSC3 and HK1 cells. When activated by ≥4.8 J cm(-2) of light, compound 1 was slightly more potent as a photosensitizer than Pha by consistently having marginally lower IC(50) values across different cell lines. In flow cytometry experiments to study the mechanism of photoactivated cell death in HSC3, compound 1 was observed to induce more pronounced apoptosis compared with Pha, which may have been driven by the transient G(2)/M cell cycle block which was also observed. These promising results on compound 1 warrant its further investigation as a clinically useful photodynamic therapy agent for head and neck cancer.