Topoisomerase II: a potential target for novel antifungal agents.
Several podophyllotoxin-related lignans have been shown to possess significant antifungal activity against a number of filamentous fungi. Initial structure-activity studies indicate this action is sensitive to change at the 4 and 4' positions of the podophyllotoxin skeleton. Good correlation has been observed between antifungal action and the ability to inhibit the relaxation of supercoiled plasmid DNA by a topoisomerase II preparation from Saccharomyces cerevisiae. Etoposide, an inhibitor of mammalian topoisomerase II, is inactive against this yeast enzyme, although good inhibition is shown by amiloride, 4'-(9-acridinylamino)-methanesulphon-m-anisidide (m-AMSA) and novobiocin, known inhibitors of the mammalian enzyme.
Figgitt
D P
DP
Department of Pharmaceutical Sciences, University of Nottingham, University Park, U.K.
Denyer
S P
SP
Dewick
P M
PM
Jackson
D E
DE
Williams
P
P
D000584:Amiloride / Q000494:pharmacology; D000677:Amsacrine / Q000494:pharmacology; D000935:Antifungal Agents; D004278:DNA, Superhelical / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D015394:Molecular Structure; D009675:Novobiocin / Q000494:pharmacology; D010957:Plasmids; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000935:Antifungal Agents; D004278:DNA, Superhelical; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D009675:Novobiocin; D005047:Etoposide; D000584:Amiloride; D011034:Podophyllotoxin