Medicinal and Biological Chemistry of Alkynylgold Complexes
Biological and Biomimetic Chemistry
Final Report Abstract
Gold and its complexes have been used in medicine since ancient times and have been applied in modern medicine for the treatment of rheumatoid arthritis for several decades. Current research focuses on the application of gold species for other diseases, such as cancer. The overarching goal of the project was to establish a new class of gold anticancer metallodrug candidates, which is based on an alkyne as ligand that is supposed to increase the stability of the complexes. Within the scope of the project alkynylgold(I) complexes with phosphane or N-heterocyclic carbene secondary ligands were investigated. For both types structure-activity-relationships as anticancer agents were established, thioredoxin reductase was confirmed as a relevant molecular target, and important properties in preclinical research, such as the stability in solution, were studied. For both types a lead compound was identified and strong antitumoral activity was observed in-vivo in a mouse xenograft model. The obtained results provide the basis for a better understanding of the potential of alkynylgold compounds as prospective cancer chemotherapeutics.
Publications
-
Luminescent alkynyl-gold(i) coumarin derivatives and their biological activity. Dalton Trans., 43(11), 4426-4436.
Arcau, Julià; Andermark, Vincent; Aguiló, Elisabet; Gandioso, Albert; Moro, Artur; Cetina, Mario; Lima, João Carlos; Rissanen, Kari; Ott, Ingo & Rodríguez, Laura
-
Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones. Molecules, 20(11), 19699-19718.
Hikisz, Paweł; Szczupak, Łukasz; Koceva-Chyła, Aneta; Guśpiel, Adam; Oehninger, Luciano; Ott, Ingo; Therrien, Bruno; Solecka, Jolanta & Kowalski, Konrad
-
Alkynyl gold(I) phosphane complexes: Evaluation of structure–activity-relationships for the phosphane ligands, effects on key signaling proteins and preliminary in-vivo studies with a nanoformulated complex. Journal of Inorganic Biochemistry, 160, 140-148.
Andermark, Vincent; Göke, Katrin; Kokoschka, Malte; Abu, el Maaty Mohamed A.; Lum, Ching Tung; Zou, Taotao; Sun, Raymond Wai-Yin; Aguiló, Elisabet; Oehninger, Luciano; Rodríguez, Laura; Bunjes, Heike; Wölfl, Stefan; Che, Chi-Ming & Ott, Ingo
-
Cobaltoceniumethynyl gold(i) as an unusual heterodinuclear bioorganometallic fragment to study the biological properties of alkynyl gold complexes. Dalton Transactions, 45(4), 1345-1348.
Vanicek, S.; Kopacka, H.; Wurst, K.; Vergeiner, S.; Kankowski, S.; Schur, J.; Bildstein, B. & Ott, I.
-
Study of the effect of the chromophore and nuclearity on the aggregation and potential biological activity of gold(I) alkynyl complexes. Inorganica Chimica Acta, 446, 189-197.
Gavara, Raquel; Aguiló, Elisabet; Schur, Julia; Llorca, Jordi; Ott, Ingo & Rodríguez, Laura
-
diploma thesis, „Alkinyl-Gold(I)-Phosphan-Komplexe als mögliche Antitumorwirkstoffe - Synthese, biologische Testung und Strukturwirkungsbeziehungen
Prause, Andre
-
A Multitarget Gold(I) Complex Induces Cytotoxicity Related to Aneuploidy in HCT‐116 Colorectal Carcinoma Cells. Angewandte Chemie International Edition, 59(38), 16795-16800.
Zhang, Jing‐Jing; Abu, el Maaty Mohamed A.; Hoffmeister, Henrik; Schmidt, Claudia; Muenzner, Julienne K.; Schobert, Rainer; Wölfl, Stefan & Ott, Ingo
-
An Erlotinib gold(I) conjugate for combating triple-negative breast cancer. Journal of Inorganic Biochemistry, 203, 110910.
Ortega, Enrique; Zamora, Ana; Basu, Uttara; Lippmann, Petra; Rodríguez, Venancio; Janiak, Christoph; Ott, Ingo & Ruiz, José
-
Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike‐ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics**. Chemistry – A European Journal, 26(66), 15140-15144.
Gil‐Moles, Maria; Basu, Uttara; Büssing, Rolf; Hoffmeister, Henrik; Türck, Sebastian; Varchmin, Agnieszka & Ott, Ingo
-
Pharmacological inhibition of thioredoxin reductase increases insulin secretion and diminishes beta cell viability. Naunyn-Schmiedeberg's Archives of Pharmacology, 394(6), 1133-1142.
Brüning, Dennis; Hatlapatka, Kathrin; Lier-Glaubitz, Verena; Andermark, Vincent; Scherneck, Stephan; Ott, Ingo & Rustenbeck, Ingo
-
PhD thesis, „Entwicklung, Synthese und biologische Untersuchung verschiedener Gold(I)-Alkin-Komplexe als potenzielle Antitumorwirkstoffe“
Varchmin, Agnieszka
-
PhD thesis, „HPLC-MS Untersuchungen von Gold-Komplexen in Lösungen und biologisch relevanten Matrizes“
Hoffmeister, Henrik
-
A simple synthetic entryway into (N‐heterocyclic carbene)gold‐steroidyl complexes and their anticancer activity. Applied Organometallic Chemistry, 38(10).
Scattolin, Thomas; Lippmann, Petra; Beliš, Marek; van Hecke, Kristof; Ott, Ingo & Nolan, Steven P.
-
Gold(Ⅰ) organometallics with alkynyl and N-heterocyclic carbene ligands and their medicinal and computational chemistry evaluation as prospective anticancer drugs. Journal of Organometallic Chemistry, 1012, 123148.
Varchmin, Agnieszka; Muñoz-Castro, Alvaro & Ott, Ingo
