title: Uptake by cells and photosensitizing effectiveness of novel pheophorbide derivatives in vitro.
abstract: Pheophorbide a prepared from the algae Spirulina was derivatized at the C(7)-carboxylic group by linking amino alkyls of various lengths and terminal functional groups. The compounds were purified by thin-layer chromatography (TLC) and by high-pressure liquid chromatography (HPLC). Solubilization of compounds by serum lipoproteins, the kinetics of compound uptake into mammalian cells, and photosensitizing effectiveness when activated by 673 nm laser light have been studied. Optimal photosensitizer uptake into cells and the greatest photosensitizing activity were observed with compounds having side-chain lengths of 4-6 carbon atoms which terminated in -OH and -CH3 groups. The most effective compounds were 3 orders of magnitude more potent than Photofrin in the degree of photoinactivation of cultured EMT-6 tumor cells. HDL and LDL significantly promoted the efflux of these photosensitizing drugs from cells, suggesting that their long-term retention in normal tissues in vivo would be minimal and produce little phototoxicity.
authors.affiliation: Department of Biochemistry, Hebrew University of Jerusalem, Hadassah School of Medicine, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Dagan
authors.forename: S
authors.initials: S
authors.lastname: Gatt
authors.forename: S
authors.initials: S
authors.lastname: Cerbu-Karabat
authors.forename: J C
authors.initials: JC
authors.lastname: Mazière
authors.forename: C
authors.initials: C
authors.lastname: Mazière
authors.forename: R
authors.initials: R
authors.lastname: Santus
authors.forename: E L
authors.initials: EL
authors.lastname: Engelhardt
authors.forename: K A
authors.initials: KA
authors.lastname: Yeh
authors.forename: C C
authors.initials: CC
authors.lastname: Stobbe
authors.forename: M C
authors.initials: MC
authors.lastname: Fenning
mesh_terms: D000818:Animals; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D056890:Eukaryota; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D010775:Photic Stimulation; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017319:Photosensitizing Agents; D002734:Chlorophyll; C032623:pheophorbide a