Photodynamic activity of plant extracts from Sarawak, Borneo.

Photodynamic therapy (PDT) is a medical treatment that involves the irradiation of an administered photosensitizing drug with light of a particular wavelength to activate the photosensitizer to kill abnormal cells. To date, only a small number of photosensitizers have been clinically approved for PDT, and researchers continue to look for new molecules that have more desirable properties for clinical applications. Natural products have long been important sources of pharmaceuticals, and there is a great potential for discovery of novel chemotypes from under-explored biodiversities in the world. The objective of this study is to mine the terrestrial plants in Sarawak, Borneo Island, for new photosensitizers for PDT. In a screening program from 2004 to 2008, we prepared and studied 2,400 extracts from 888 plants for their photosensitizing activities. This report details the bioprospecting process, preparation and testing of extracts, analysis of the active samples, fractionation of four samples, and isolation and characterization of photosensitizers.

Derivatives of pheophorbide-a and pheophorbide-b from photocytotoxic Piper penangense extract.

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).

The neovessel occlusion efficacy of 15-hydroxypurpurin-7-lactone dimethyl ester induced with photodynamic therapy.

In this study, the photodynamic therapy (PDT) induced efficacy of a semi-synthesized analogue 15(1)-hydroxypurpurin-7-lactone dimethyl ester or G2, in terms of chick chorioallantoic membrane blood vessel occlusion was evaluated in reference to verteporfin. Early formulation studies showed that G2 prepared in a system of cremophor EL 2.5% and ethanol 2.5% in saline was biocompatible up to 20 microL volume of injection. Following injection, G2 accumulation peaked within the first minute and its extravasation from intra- to extra-vascular occurred somewhat slower as compared with verteporfin. In the PDT study, closure of capillaries and small neovessels was observed with 4 microg per embryo of G2 and a light dose of 20 J cm(-2) at a fluence rate of 40 mW cm(-2) filtered at 400-440 nm-a result that may be considered optimum for the treatment of age-related macular degeneration (AMD). Also, partial occlusion of the large vessels was observed using the same dose of G2 and light-an effect which is desirable for cancer treatment. From this study, we conclude that G2 has the potential to be developed as a therapeutic agent for photodynamic treatment for AMD and cancer.