title: Structural simplification of bioactive natural products with multicomponent synthesis: dihydropyridopyrazole analogues of podophyllotoxin.
abstract: 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.
authors.affiliation: Department of Organic Chemistry, Timiryazev Agriculture Academy, Moscow 127550, Russia. intelbioscan@mtu-net.ru
authors.forename: Igor V
authors.initials: IV
authors.lastname: Magedov
authors.forename: Madhuri
authors.initials: M
authors.lastname: Manpadi
authors.forename: Elena
authors.initials: E
authors.lastname: Rozhkova
authors.forename: Nikolai M
authors.initials: NM
authors.lastname: Przheval'skii
authors.forename: Snezna
authors.initials: S
authors.lastname: Rogelj
authors.forename: Scott T
authors.initials: ST
authors.lastname: Shors
authors.forename: Wim F A
authors.initials: WF
authors.lastname: Steelant
authors.forename: Severine
authors.initials: S
authors.lastname: Van slambrouck
authors.forename: Alexander
authors.initials: A
authors.lastname: Kornienko
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D011720:Pyrazoles; D011034:Podophyllotoxin