title: Dimers of Melampomagnolide B Exhibit Potent Anticancer Activity against Hematological and Solid Tumor Cells.
abstract: Novel carbamate (7a-7h) and carbonate (7i, 7j, and 8) dimers of melampomagnolide B have been synthesized by reaction of the melampomagnolide-B-triazole carbamate synthon 6 with various terminal diamino- and dihydroxyalkanes. Dimeric carbamate products 7b, 7c, and 7f exhibited potent growth inhibition (GI50 = 0.16-0.99 μM) against the majority of cell lines in the NCI panel of 60 human hematological and solid tumor cell lines. Compound 7f and 8 exhibited anticancer activity that was 300-fold and 1 × 10(6)-fold more cytotoxic than DMAPT, respectively, at a concentration of 10 μM against rat 9L-SF gliosarcoma cells. Compounds 7a-7j and 8 were also screened against M9-ENL1 and acute myelogenous leukemia (AML) primary cell lines and exhibited 2- to 10-fold more potent antileukemic activity against M9-ENL1 cells (EC50 = 0.57-2.90 μM) when compared to parthenolide (EC50 = 6.0) and showed potent antileukemic activity against five primary AML cell lines (EC50 = 0.76-7.3 μM).
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and ‡Department of Radiology and Neurology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, United States.|Division of Hematology and §Department of Toxicology, University of Colorado , Aurora, Colorado 80045, United States.
authors.forename: Venumadhav
authors.initials: V
authors.lastname: Janganati
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and ‡Department of Radiology and Neurology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, United States.|Division of Hematology and §Department of Toxicology, University of Colorado , Aurora, Colorado 80045, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ponder
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and ‡Department of Radiology and Neurology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, United States.|Division of Hematology and §Department of Toxicology, University of Colorado , Aurora, Colorado 80045, United States.
authors.forename: Craig T
authors.initials: CT
authors.lastname: Jordan
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and ‡Department of Radiology and Neurology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, United States.|Division of Hematology and §Department of Toxicology, University of Colorado , Aurora, Colorado 80045, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borrelli
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and ‡Department of Radiology and Neurology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, United States.|Division of Hematology and §Department of Toxicology, University of Colorado , Aurora, Colorado 80045, United States.
authors.forename: Narsimha Reddy
authors.initials: NR
authors.lastname: Penthala
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and ‡Department of Radiology and Neurology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, United States.|Division of Hematology and §Department of Toxicology, University of Colorado , Aurora, Colorado 80045, United States.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019281:Dimerization; D004354:Drug Screening Assays, Antitumor; D018316:Gliosarcoma / Q000188:drug therapy; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D061251:Primary Cell Culture; D051381:Rats; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014410:Tumor Stem Cell Assay
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012717:Sesquiterpenes; C558241:melampomagnolide B; C002669:parthenolide