Antitumor psoropermum xanthones and sarcomelicope acridones: privileged structures implied in DNA alkylation.
Fused isopropylfuran and dimethylpyran units are privileged structures present in numerous bioactive natural products exemplified, in the field of anticancer drugs, by the furanoxanthone psorospermin and the pyranoacridone acronycine. Psorospermin binds to the N-7 position of the guanine units in the presence of topoisomerase II. In contrast, acronycine derivatives such as cis-1,2-diacetoxy-1,2-dihydrobenzo[b]acronycine alkylate the 2-amino group of DNA guanine residues in the minor groove. Hybrid compounds associating the acridone or benzo[b]acridone chromophore of acronycine derivatives and the epoxyfuran alkylating unit present in psorospermin also display very potent antiproliferative activities, alkylating DNA guanine units at position N-7 in the major groove, as natural xanthones belonging to the psorospermin series.
Nguyen
Hung The
HT
Laboratoire de Pharmacognosie de l'Universite Paris Descartes, UMR/CNRS 8638, 4 Avenue de l'Observatoire, F-75006 Paris, France.
Lallemand
Marie-Christine
MC
Boutefnouchet
Sabrina
S
Michel
Sylvie
S
Tillequin
François
F
D000175:Acronine / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D004249:DNA Damage; D015394:Molecular Structure; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
D001688:Biological Products; D044004:Xanthones; C025543:psorospermin; D000175:Acronine