Cytotoxicity and DNA-binding property of non-diynene class of dynemicins and aza-anthraquinones.
Dynemicin A is a potent antibacterial and antitumor antibiotic having a striking hybrid structure of both anthraquinone as a DNA intercalator and diynene as a DNA strand breaker. We have investigated the DNA-binding property and cytotoxicity of non-diynene class of dynemicins (H, L, M, O and Q) and several related synthetic tri- and pentacyclic aza-anthraquinones 1a-3a (R = H) and 1b-3b (R = CH3). Among them, dynemicin H, L, M, O, Q, 1a, 1b and 2b exhibited DNA-binding property. All non-diynene class of dynemicins investigated exhibited intercalative binding activity, however, synthetic aza-anthraquinones 1a-3a did not show such ability. Dynemicin H, Q, 2a, 2b and 3b showed cytotoxicity against HL-60 and K-562 cell lines.
Shirai
R
R
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Shimazawa
R
R
Shichita
M
M
Takahashi
M
M
Hashimoto
Y
Y
Iwasaki
S
S
D000475:Alkenes; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001372:Aza Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004278:DNA, Superhelical / Q000378:metabolism; D053281:Enediynes; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D014407:Tumor Cells, Cultured
D000475:Alkenes; D000880:Anthraquinones; D000903:Antibiotics, Antineoplastic; D001372:Aza Compounds; D004278:DNA, Superhelical; D053281:Enediynes; C071792:dynemicin M; C068022:dynemicin H; C071791:dynemicin O; C071789:dynemicin Q; D004247:DNA; C061229:dynemicin A