Highly Cytotoxic Molybdenocenes with Strong Metabolic Effects Inhibit Tumour Growth in Mice

Valentin Fuchs; Klaudia Cseh; Michaela Hejl; Petra Vician; Benjamin Neuditschko; Samuel M. Meier-Menches; Lukas Janker; Andrea Bileck; Natalie Gajic; Julia Kronberger; Martin Schaier; Sophie Neumayer; Gunda Köllensperger; Christopher Gerner; Walter Berger; Michael A. Jakupec; Michael S. Malarek; Bernhard K. Keppler

doi:10.1002/chem.202202648

Highly Cytotoxic Molybdenocenes with Strong Metabolic Effects Inhibit Tumour Growth in Mice

Valentin Fuchs, Klaudia Cseh, Michaela Hejl, Petra Vician, Benjamin Neuditschko, Samuel M. Meier-Menches, Lukas Janker, Andrea Bileck, Natalie Gajic, Julia Kronberger, Martin Schaier, Sophie Neumayer, Gunda Köllensperger, Christopher Gerner, Walter Berger, Michael A. Jakupec, Michael S. Malarek, Bernhard K. Keppler

Publikation: Beitrag in Fachzeitschrift › Artikel › Begutachtung

Abstract

A series of six highly lipophilic Cp-substituted molybdenocenes bearing different bioactive chelating ligands was synthesized and characterized by NMR spectroscopy, mass spectrometry and X-ray crystallography. In vitro experiments showed a greatly increased cytotoxic potency when compared to the non-Cp-substituted counterparts. In vivo experiments performed with the dichlorido precursor, (Ph₂C−Cp)₂MoCl₂ and the in vitro most active complex, containing the thioflavone ligand, showed an inhibition of tumour growth. Proteomic studies on the same two compounds demonstrated a significant regulation of tubulin-associated and mitochondrial inner membrane proteins for both compounds and a strong metabolic effect of the thioflavone containing complex.

Originalsprache	Englisch
Aufsatznummer	e202202648
Seiten (von - bis)	e202202648
Fachzeitschrift	Chemistry - A European Journal
Jahrgang	29
Ausgabenummer	4
DOIs	https://doi.org/10.1002/chem.202202648
Publikationsstatus	Veröffentlicht - 18 Jän. 2023
Extern publiziert	Ja

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Fuchs, V., Cseh, K., Hejl, M., Vician, P., Neuditschko, B., Meier-Menches, S. M., Janker, L., Bileck, A., Gajic, N., Kronberger, J., Schaier, M., Neumayer, S., Köllensperger, G., Gerner, C., Berger, W., Jakupec, M. A., Malarek, M. S., & Keppler, B. K. (2023). Highly Cytotoxic Molybdenocenes with Strong Metabolic Effects Inhibit Tumour Growth in Mice. Chemistry - A European Journal, 29(4), e202202648. Artikel e202202648. https://doi.org/10.1002/chem.202202648

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title = "Highly Cytotoxic Molybdenocenes with Strong Metabolic Effects Inhibit Tumour Growth in Mice",

abstract = "A series of six highly lipophilic Cp-substituted molybdenocenes bearing different bioactive chelating ligands was synthesized and characterized by NMR spectroscopy, mass spectrometry and X-ray crystallography. In vitro experiments showed a greatly increased cytotoxic potency when compared to the non-Cp-substituted counterparts. In vivo experiments performed with the dichlorido precursor, (Ph2C−Cp)2MoCl2 and the in vitro most active complex, containing the thioflavone ligand, showed an inhibition of tumour growth. Proteomic studies on the same two compounds demonstrated a significant regulation of tubulin-associated and mitochondrial inner membrane proteins for both compounds and a strong metabolic effect of the thioflavone containing complex.",

keywords = "anticancer, biological tests (in vitro and in vivo), bioorganometallic chemistry, molybdenocenes, proteomics, Chelating Agents/chemistry, Crystallography, X-Ray, Neoplasms, Antineoplastic Agents/pharmacology, Animals, Proteomics, Cell Line, Tumor, Ligands, Mice, Molecular Structure",

author = "Valentin Fuchs and Klaudia Cseh and Michaela Hejl and Petra Vician and Benjamin Neuditschko and Meier-Menches, {Samuel M.} and Lukas Janker and Andrea Bileck and Natalie Gajic and Julia Kronberger and Martin Schaier and Sophie Neumayer and Gunda K{\"o}llensperger and Christopher Gerner and Walter Berger and Jakupec, {Michael A.} and Malarek, {Michael S.} and Keppler, {Bernhard K.}",

note = "{\textcopyright} 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.",

year = "2023",

month = jan,

day = "18",

doi = "10.1002/chem.202202648",

language = "English",

volume = "29",

pages = "e202202648",

journal = "Chemistry - A European Journal",

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Fuchs, V, Cseh, K, Hejl, M, Vician, P, Neuditschko, B, Meier-Menches, SM, Janker, L, Bileck, A, Gajic, N, Kronberger, J, Schaier, M, Neumayer, S, Köllensperger, G, Gerner, C, Berger, W, Jakupec, MA, Malarek, MS & Keppler, BK 2023, 'Highly Cytotoxic Molybdenocenes with Strong Metabolic Effects Inhibit Tumour Growth in Mice', Chemistry - A European Journal, Jg. 29, Nr. 4, e202202648, S. e202202648. https://doi.org/10.1002/chem.202202648

TY - JOUR

T1 - Highly Cytotoxic Molybdenocenes with Strong Metabolic Effects Inhibit Tumour Growth in Mice

AU - Fuchs, Valentin

AU - Cseh, Klaudia

AU - Hejl, Michaela

AU - Vician, Petra

AU - Neuditschko, Benjamin

AU - Meier-Menches, Samuel M.

AU - Janker, Lukas

AU - Bileck, Andrea

AU - Gajic, Natalie

AU - Kronberger, Julia

AU - Schaier, Martin

AU - Neumayer, Sophie

AU - Köllensperger, Gunda

AU - Gerner, Christopher

AU - Berger, Walter

AU - Jakupec, Michael A.

AU - Malarek, Michael S.

AU - Keppler, Bernhard K.

PY - 2023/1/18

Y1 - 2023/1/18

N2 - A series of six highly lipophilic Cp-substituted molybdenocenes bearing different bioactive chelating ligands was synthesized and characterized by NMR spectroscopy, mass spectrometry and X-ray crystallography. In vitro experiments showed a greatly increased cytotoxic potency when compared to the non-Cp-substituted counterparts. In vivo experiments performed with the dichlorido precursor, (Ph2C−Cp)2MoCl2 and the in vitro most active complex, containing the thioflavone ligand, showed an inhibition of tumour growth. Proteomic studies on the same two compounds demonstrated a significant regulation of tubulin-associated and mitochondrial inner membrane proteins for both compounds and a strong metabolic effect of the thioflavone containing complex.

AB - A series of six highly lipophilic Cp-substituted molybdenocenes bearing different bioactive chelating ligands was synthesized and characterized by NMR spectroscopy, mass spectrometry and X-ray crystallography. In vitro experiments showed a greatly increased cytotoxic potency when compared to the non-Cp-substituted counterparts. In vivo experiments performed with the dichlorido precursor, (Ph2C−Cp)2MoCl2 and the in vitro most active complex, containing the thioflavone ligand, showed an inhibition of tumour growth. Proteomic studies on the same two compounds demonstrated a significant regulation of tubulin-associated and mitochondrial inner membrane proteins for both compounds and a strong metabolic effect of the thioflavone containing complex.

KW - anticancer

KW - biological tests (in vitro and in vivo)

KW - bioorganometallic chemistry

KW - molybdenocenes

KW - proteomics

KW - Chelating Agents/chemistry

KW - Crystallography, X-Ray

KW - Neoplasms

KW - Antineoplastic Agents/pharmacology

KW - Animals

KW - Proteomics

KW - Cell Line, Tumor

KW - Ligands

KW - Mice

KW - Molecular Structure

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U2 - 10.1002/chem.202202648

DO - 10.1002/chem.202202648

M3 - Article

C2 - 36222279

AN - SCOPUS:85143269756

SN - 0947-6539

VL - 29

SP - e202202648

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 4

M1 - e202202648