title: Synthesis and biological evaluation of prodigiosene conjugates of porphyrin, estrone and 4-hydroxytamoxifen.
abstract: To generate the first series of prodigiosene conjugates, the tripyrrolic skeleton was appended to estrone, tamoxifen and porphyrin frameworks by way of ester linkers and various hydrocarbon chain lengths. The ability of the conjugates to inhibit various types of cancer cells was evaluated in vitro. The porphyrin conjugates did not exhibit significant activity. The estrone conjugates exhibited modest activity, for the most part. However, significantly greater growth inhibition activity against certain breast, colon, lung, leukemia, melanoma and prostate cell lines was noted. This unusual effect for this first generation model class of compound warrants further investigation and comparison to cases where estrogens are linked to prodigiosenes via connection points that do not feature in estrogen receptor binding. The 4-hydroxytamoxifen conjugates exhibit nanomolar range activity against the MCF-7 breast cancer cell line, paving the way to expand the scope and connectivity of prodigiosene-tamoxifen conjugates.
authors: Department of Chemistry, Dalhousie University, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors: Cassandra L A
authors: CL
authors: Hawco
authors: Estelle
authors: E
authors: Marchal
authors: Md Imam
authors: MI
authors: Uddin
authors: Alexander E G
authors: AE
authors: Baker
authors: Dale P
authors: DP
authors: Corkery
authors: Graham
authors: G
authors: Dellaire
authors: Alison
authors: A
authors: Thompson
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004970:Estrone / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D011166:Porphyrins / Q000737:chemistry*; D011353:Prodigiosin / Q000737:chemistry*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D011166:Porphyrins; D013629:Tamoxifen; C016601:afimoxifene; D004970:Estrone; D011353:Prodigiosin
keywords: Anticancer; Drug-targeting; Estrone; Natural product; Porphyrin; Prodigiosenes; Tamoxifen