Novel selective inhibitors for human topoisomerase I, BM2419-1 and -2 derived from saintopin.
Compounds BM2419-1 and -2 were isolated from a culture broth of a fungus Paecilomyces sp. BM2419. It was shown that these novel compounds were artifacts derived from saintopin, a dual inhibitor of topoisomerase I and II by independent processes. In the human topoisomerase I inhibition assay using the recombinant Saccharomyces cerevisiae, BM2419-1 and -2 inhibited selectively the yeast growth dependent on human topoisomerase I induction with IC50 values of 0.3 ng/ml and 6.0 ng/ml, respectively.
Drug Discovery Research Laboratories, Kaken Pharmaceutical CO., LTD., Shizuoka, Japan.
D
D
Ishiyama
K
K
Futamata
M
M
Futamata
O
O
Kasuya
S
S
Kamo
F
F
Yamashita
S
S
Kanazawa
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001551:Benz(a)Anthracenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010143:Paecilomyces / Q000737:chemistry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C117811:BM 2419-1; C117812:BM 2419-2; D001551:Benz(a)Anthracenes; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D059004:Topoisomerase I Inhibitors; C066552:saintopin; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin