Structural simplification of bioactive natural products with multicomponent synthesis: dihydropyridopyrazole analogues of podophyllotoxin.
A three-component condensation of 5-amino-3-methylpyrazole, tetronic acid, and various aromatic, heteroaromatic, and aliphatic aldehydes leads to the formation of dihydropyridopyrazole analogues of a cytotoxic lignan podophyllotoxin. This new heterocyclic scaffold-based library allows a drastic reduction of the structural complexity of the natural product with the retention of its potent cytotoxic properties. Similarly to podophyllotoxin, the presented analogues induce apoptosis in Jurkat cells.
Magedov
Igor V
IV
Department of Organic Chemistry, Timiryazev Agriculture Academy, Moscow 127550, Russia. intelbioscan@mtu-net.ru
Manpadi
Madhuri
M
Rozhkova
Elena
E
Przheval'skii
Nikolai M
NM
Rogelj
Snezna
S
Shors
Scott T
ST
Steelant
Wim F A
WF
Van slambrouck
Severine
S
Kornienko
Alexander
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000138:chemical synthesis*; D006801:Humans; D019169:Jurkat Cells; D008722:Methods; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001688:Biological Products; D011720:Pyrazoles; D011034:Podophyllotoxin