title: Antitumor agents. Part 209: Pheophorbide-a derivatives as photo-Independent cytotoxic agents.
abstract: A methanolic crude extract of the plant Garuga pinnata Roxb. (Burseraceae) showed promising cytotoxic activity against a panel of human tumor cell lines in vitro, including KB and its drug-resistant sublines (Ferguson et al. Cancer Res. 1988, 48, 5956). Pheophorbide-a and-b methyl esters (3,4) were isolated as active principles with broad photo-dependent cytotoxic activities in the micromolar range. These findings prompted SAR studies of known and novel pheophorbide-a derivatives as photo-dependent and photo-independent cytotoxic agents. The results showed that zinc-protoporphyrin IX (10), zinc 13(R)-hydroxypheophorbide-a methyl ester (22), and zinc chlorin-e6 trimethyl ester (13) possessed photo-independent cytotoxic activity. Compounds 13 and 22 were the most active cytotoxic agents of the series (mean ED(50) 4.6 +/- 1.0 microM and 5.7 +/- 0.7 microM, respectively) against KB cells incubated in the dark.
authors.affiliation: Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
authors.forename: Prapai
authors.initials: P
authors.lastname: Wongsinkongman
authors.forename: Arnold
authors.initials: A
authors.lastname: Brossi
authors.forename: Hui-Kang
authors.initials: HK
authors.lastname: Wang
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D002735:Chlorophyllides; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008027:Light; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology; D011524:Protoporphyrins / Q000737:chemistry / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002735:Chlorophyllides; D011166:Porphyrins; D011524:Protoporphyrins; D011838:Radiation-Sensitizing Agents; D002734:Chlorophyll; C062985:phytochlorin; C028025:protoporphyrin IX; C032623:pheophorbide a; D015032:Zinc