title: Oxazolinodoxorubicin - a promising new anthracycline.
abstract: Oxazolinodoxorubicin, a doxorubicin analog with a modified daunosamine moiety was synthesized. The properties of this compound and the parent doxorubicin were compared. The cytotoxicity in vitro studies against several human tumor cell lines (PC-3, MCF-7, SW707, HL-60, RPMI 8226, ACHN) showed higher antiproliferative potency for this new compound. Moreover, its ability to completely overcome the drug resistance of cancer cells in vitro was revealed (LoVo, LoVo/DX, MES-SA, MES-SA/DX5, HL-60, HL-60/Vinc, HL-60/MX2 cell lines). Cellular uptake analyzed on HL-60 and HL-60/MX2 cells, demonstrated higher penetration levels of oxazolinodoxorubicin compared to that of doxorubicin. In animal experiments, general toxicity of oxazolinodoxorubicin was lower than that observed for doxorubicin. Furthermore, similar antitumor effects was observed in NOD/SCID mice bearing resistant HL-60/Vinc leukemia tumor and in mice treated with the new or parent compounds. The presented results suggest that oxazolinodoxorubicin is a new anthracycline with an advantageous biological activity profile.
authors: Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, 5 Staroscinska St., 02-516 Warsaw, Poland. lukawskam@iba.waw.pl
authors: Malgorzata
authors: M
authors: Lukawska
authors: Dagmara
authors: D
authors: Klopotowska
authors: Magdalena
authors: M
authors: Milczarek
authors: Joanna
authors: J
authors: Wietrzyk
authors: Kazimierz
authors: K
authors: Studzian
authors: Leszek
authors: L
authors: Szmigiero
authors: Anna
authors: A
authors: Porebska
authors: Irena
authors: I
authors: Oszczapowicz
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; C552952:oxazolinodaunorubicin; D004317:Doxorubicin; D003630:Daunorubicin