A chemical-biological study reveals C9-type iridoids as novel heat shock protein 90 (Hsp90) inhibitors.
The potential of heat shock protein 90 (Hsp90) as a therapeutic target for numerous diseases has made the identification and optimization of novel Hsp90 inhibitors an emerging therapeutic strategy. A surface plasmon resonance (SPR) approach was adopted to screen some iridoids for their Hsp90 α binding capability. Twenty-four iridoid derivatives, including 13 new natural compounds, were isolated from the leaves of Tabebuia argentea and petioles of Catalpa bignonioides. Their structures were elucidated by NMR, electrospray ionization mass spectrometry, and chemical methods. By means of a panel of chemical and biological approaches, four iridoids were demonstrated to bind Hsp90 α. In particular, the dimeric iridoid argenteoside A was shown to efficiently inhibit the chaperone in biochemical and cellular assays. Our results disclose C9-type iridoids as a novel class of Hsp90 inhibitors.
Dipartimento di Farmacia, Università di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy.
Fabrizio
F
Dal Piaz
Antonio
A
Vassallo
Abeer
A
Temraz
Roberta
R
Cotugno
Maria A
MA
Belisario
Giuseppe
G
Bifulco
Maria G
MG
Chini
Claudio
C
Pisano
Nunziatina
N
De Tommasi
Alessandra
A
Braca
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D029402:Bignoniaceae / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002950:Citrate (si)-Synthase / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006367:HeLa Cells; D006801:Humans; D039823:Iridoids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D007700:Kinetics; D062105:Molecular Docking Simulation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D039823:Iridoids; D002950:Citrate (si)-Synthase; D000251:Adenosine Triphosphatases