title: Improved synthesis of N-benzylaminoferrocene-based prodrugs and evaluation of their toxicity and antileukemic activity.
abstract: We report on an improved method of synthesis of N-benzylaminoferrocene-based prodrugs and demonstrate its applicability by preparing nine new aminoferrocenes. Their effect on the viability of selected cancer cells having different p53 status was studied. The obtained data are in agreement with the hypothesis that the toxicity of aminoferrocenes is not dependent upon p53 status. Subsequently the toxicity of a selected prodrug (4) was investigated ex vivo using rat precision cut liver slices and in vivo on hybrid male mice BDF1. In both experiments no toxicity was observed: ex vivo, up to 10 μM; in vivo, up to 6 mg/kg. Finally, prodrug 4 was shown to extend the survival of BDF1 mice carrying L1210 leukemia from 13.7 ± 0.6 days to 17.5 ± 0.7 days when injected daily 6 times at a dose of 26 μg/kg starting from the second day after injection of L1210 cells.
authors: Department of Chemistry and Pharmacy, Organic Chemistry II, Friedrich-Alexander-University of Erlangen-Nürnberg , Henkestraße 42, 91054 Erlangen, Germany.
authors: Steffen
authors: S
authors: Daum
authors: Vasiliy F
authors: VF
authors: Chekhun
authors: Igor N
authors: IN
authors: Todor
authors: Natalia Yu
authors: NY
authors: Lukianova
authors: Yulia V
authors: YV
authors: Shvets
authors: Leopold
authors: L
authors: Sellner
authors: Kerstin
authors: K
authors: Putzker
authors: Joe
authors: J
authors: Lewis
authors: Thorsten
authors: T
authors: Zenz
authors: Inge A M
authors: IA
authors: de Graaf
authors: Geny M M
authors: GM
authors: Groothuis
authors: Angela
authors: A
authors: Casini
authors: Oleksii
authors: O
authors: Zozulia
authors: Frank
authors: F
authors: Hampel
authors: Andriy
authors: A
authors: Mokhir
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007938:Leukemia / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D005296:Ferrous Compounds; D011355:Prodrugs