Synthesis and cytotoxic activity of psorospermin and acronycine analogues in the 3-propyloxy-acridin-9(10H)-one and -benzo[b]acridin-125H-one series.
In order to explore the structure-activity relationships in the acronycine and psorospermin series, simplified analogues of the highly cytotoxic (+/-)-(2R*,1'R*)-5-methoxy-11-methyl-2-(2-methyloxiran-2-yl)-1,2-dihydro-11H-furo[2,3-c]acridin-6-one and (+/-)-(2R*,1'R*)-5-methoxy-13-methyl-2-(2-methyloxiran-2-yl)-1,2-dihydro-13H-benzo[b]furo[3,2-h]-acridin-6-one lacking the fused furan ring, including 3-allyloxy-1-methoxy-10-methyl-acridin-9(10H)-one, 3-allyloxy-1-methoxy-5-methyl-benzo[b]acridin-12(5H)-one, the corresponding epoxides, and related dihydrodiol esters and diesters were prepared. Only the simplified oxirane compounds displayed significant antiproliferative activity compared to the parent compounds. The oxirane alkylating unit appears indispensible to observe significant antiproliferative activity in both series, but the presence of the angularly fused furan ring does not appear as a crucial structural requirement to observe significant cytotoxic activity.
Boutefnouchet
Sabrina
S
Laboratoire de Pharmacognosie de l'Université Paris Descartes, UMR/CNRS n degrees 8638, Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006 Paris, France.
Minh
Nguyen Tuan
NT
Putrus
Rana
R
Pfeiffer
Bruno
B
Léonce
Stéphane
S
Pierré
Alain
A
Michel
Sylvie
S
Tillequin
François
F
Lallemand
Marie-Christine
MC
D000175:Acronine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000737:chemistry*
D000970:Antineoplastic Agents; D044004:Xanthones; C025543:psorospermin; D000175:Acronine