title: Derivatives of pheophorbide-a and pheophorbide-b from photocytotoxic Piper penangense extract.
abstract: 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).
authors.affiliation: Cancer Research Initiatives Foundation, Sime Darby Medical Center, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia.
authors.forename: Fadzly Adzhar
authors.initials: FA
authors.lastname: Kamarulzaman
authors.forename: Khozirah
authors.initials: K
authors.lastname: Shaari
authors.forename: Anthony Siong Hock
authors.initials: AS
authors.lastname: Ho
authors.forename: Nordin Haji
authors.initials: NH
authors.lastname: Lajis
authors.forename: Soo Hwang
authors.initials: SH
authors.lastname: Teo
authors.forename: Hong Boon
authors.initials: HB
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D026321:Piperaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017319:Photosensitizing Agents; D010936:Plant Extracts; D002734:Chlorophyll; C032624:pheophorbide b; C032623:pheophorbide a