title: Bismuth nitrate-induced novel nitration of estradiol: an entry to new anticancer agents.
abstract: Direct nitration of estradiol was carried out using metal nitrates on solid surfaces under mild condition, and a combination of bismuth nitrate pentahydrate impregnated KSF clay was found to be the best reagent to synthesize 2- and 4-nitroestradiol effectively. Furthermore, various basic side chains were introduced, through O-linker at C-3, to these nitroestradiols. The ability of these derivatives to cause cytotoxicity in Estrogen Receptor (ER)-positive and ER-negative breast cancer cell lines, as well as cancer cell lines of other origins, was examined. Qualitative structure activity relationship (SAR) has also been studied. We found that a basic side chain containing either a piperidine or morpholine ring, when conjugated to 2-nitroestradiol, was particularly effective at causing cytotoxicity in each of the cancer cell lines examined. Surprisingly, this effective cytotoxicity was even seen in ER-negative breast cancer cells.
authors.affiliation: Department of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78539, USA. Electronic address: banyopad@utpa.edu.
authors.forename: Debasish
authors.initials: D
authors.lastname: Bandyopadhyay
authors.affiliation: Centro de Biotecnologia Genomica, Instituto Politecnico Nacional, Blvd. del Maestro, s/n, esq. Elias Piña, Col. Narciso Mendoza, 88710 Reynosa, Mexico.
authors.forename: Gildardo
authors.initials: G
authors.lastname: Rivera
authors.affiliation: Department of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78539, USA; University of Texas Health Science Center at San Antonio, Regional Academic Health Center, Medical Research Division, 1214 West Schunior Street, Edinburg, TX 78541, USA.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Sanchez
authors.affiliation: Department of Biology, The University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78539, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Rivera
authors.affiliation: University of Texas Health Science Center at San Antonio, Regional Academic Health Center, Medical Research Division, 1214 West Schunior Street, Edinburg, TX 78541, USA.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Granados
authors.affiliation: Department of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78539, USA; University of Texas Health Science Center at San Antonio, Regional Academic Health Center, Medical Research Division, 1214 West Schunior Street, Edinburg, TX 78541, USA.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Guerrero
authors.affiliation: University of Texas Health Science Center at San Antonio, Regional Academic Health Center, Medical Research Division, 1214 West Schunior Street, Edinburg, TX 78541, USA.
authors.forename: Fang-Mei
authors.initials: FM
authors.lastname: Chang
authors.affiliation: Department of Biology, The University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78539, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Dearth
authors.affiliation: University of Texas Health Science Center at San Antonio, Regional Academic Health Center, Medical Research Division, 1214 West Schunior Street, Edinburg, TX 78541, USA; Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Electronic address: shortj@uthscsa.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Short
authors.affiliation: Department of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78539, USA.
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Banik
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001729:Bismuth / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009566:Nitrates / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009566:Nitrates; C065545:bismuth nitrate; D004958:Estradiol; D001729:Bismuth
keywords: Anticancer; Apoptosis; Bismuth nitrate; Estradiol; Estrogen receptor; Nitration; Solid-support