Synthesis, conformational analysis, and cytotoxicity of new analogues of the natural cyclodepsipeptide jaspamide.
Three analogues of the natural bioactive cyclodepsipeptide jaspamide (3-5) were efficiently synthesized using a combination of solid and solution phase techniques. The preliminary design of the molecules has involved the rational substitution and/or simplification of the most critical structural features of the lead compound. The synthetic products were subjected to pharmacological assays, and the conformational properties were investigated by MM (molecular mechanics) and MD (molecular dynamics) calculations, to describe the potential pharmacophoric core responsible for the observed activities.
Terracciano
Stefania
S
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy.
Bruno
Ines
I
Bifulco
Giuseppe
G
Copper
Jean E
JE
Smith
Charles D
CD
Gomez-Paloma
Luigi
L
Riccio
Raffaele
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C057531:jasplakinolide