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Journalartikel - Wissenschaftlicher Artikel | | Peer reviewed

Synthesis and Cytotoxic Activities of Goniothalamins and Derivatives

Autor*innen
Weber, Anja ; Döhl, Katja ; Sachs, Julia ; Nordschild, Anja C. M. ; Schröder, Dennis ; Teusch, Nicole ; Kulik, Andrea ; Fischer, Thomas ; Schmitt, Lutz ; Pietruszka, Jörg
Zeitschrift
Bioorganic & medicinal chemistry 
DOI
10.1016/j.bmc.2017.02.004

Weitere Details

Sprache
englisch
Darstellungsform
Text
Band
25
Ausgabe
22
Seitenbereich
6115 - 6125
Schlüsselwörter
A549 Cells , Antineoplastic Agents/chemical synthesis/chemistry/pharmacology/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Lactones/chemistry , MCF-7 Cells , Pyrones/chemical synthesis/chemistry/pharmacology/toxicity , Stereoisomerism , Structure-Activity Relationship

Substituted goniothalamins containing cyclopropane-groups were efficiently prepared in high yields and good selectivity. Antiproliferative activity was measured on three human cancer cell lines (A549, MCF-7, HBL-100), to show which of the structural elements of goniothalamins is mandatory for cytotoxicity. We found that the configuration of the stereogenic centre of the δ-lactone plays an important role for cytotoxicity. In our studies only (R)-configured goniothalamins showed antiproliferative activity, whereby (R)-configuration accords to natural goniothalamin (R)-1. Additionally, the δ-lactone needs to be unsaturated whereas our results show that the vinylic double bond is not mandatory for cytotoxicity. Furthermore, with a two-fold in vitro and in vivo strategy, we determined the inhibitory effect of the compounds to the yeast protein Pdr5. Here, we clearly demonstrate that the configuration seems to be of minor influence, only, while the nature of the substituent of the phenyl ring is of prime importance.

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