Enhancement of antiproliferative activity by molecular simplification of catalpol.
Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed alpha-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38-1.86muM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G(1) phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining.
Instituto Universitario de Bio-Orgánica 'Antonio González' (IUBO-AG), Universidad de La Laguna, C/Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain. cgargon@ull.es
Celina
C
García
Leticia G
LG
León
Carlos R
CR
Pungitore
Carla
C
Ríos-Luci
Antonio H
AH
Daranas
Juan C
JC
Montero
Atanasio
A
Pandiella
Carlos E
CE
Tonn
Víctor S
VS
Martín
José M
JM
Padrón
D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D057888:Iridoid Glucosides; D039823:Iridoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D017304:Annexin A5; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005960:Glucosides; D057888:Iridoid Glucosides; D039823:Iridoids; C078040:catalpol