Arbeitsgruppe Professor Dr. Ingo Ott

 

	Research		Jobs/internships/Erasmus
	Group/contact		Publications

 

 

Research

Development of New Cytostatics

Medicinal Chemistry of Metal Complexes

 

Mission

Among the currently used therapeutic drugs only a small minority contain metal atoms. However, the continuing success story of the platinum antitumor drugs (e.g. cisplatin and carboplatin) as well as the promising preclinical results of various other coordination compounds, demonstrate that metal species can be valuable therapeutics. Additionally, over the last decades the fast progress in inorganic and organometallic chemistry has provided a large pool of new chemical functionalities, which can be utilised in medicinal chemistry as partial structures of new drugs.

Within this scope our research projects are mainly focused on the development of new inorganic or organometallic drugs, the establishing of metal based pharmacophores as well as the investigation of the biological functions of metal complexes.

 

Methods

Besides synthetic chemistry and structural characterisation of new antitumor drugs we strongly focus on an intensive biological evaluation of the new compounds. Relevant experimental procedures include the analysis of proliferation and apoptosis, bioanalytical studies (e.g. quantification of the cellular uptake) and various enzymatic assays. A special focus of the group is on the use of high resolution continuum source atomic absorption spectroscopy (HR-CS AAS) to study the biodistribution of metal coordination compounds in-vitro.

 

Recent Results

Metal complexes with N-heterocyclic carbene (NHC) ligands can be used to design new anticancer drugs. For a series of gold(I) NHC complexes of the benzimidazolylidene type (see structures in the above figure) we could observe interesting biological effects such as a strong proliferation inhibition, apoptosis induction or inhibition of the enzyme thioredoxin reductase. Biodistribution studies showed that the cellular uptake and trafficking into mitochondria were of relevance for the observed effects.

 

read more:

            AuNHC-report-2011

            AuNHC-report-2010

 

Fundings

Our projects are currently supported by DFG (Deutsche Forschungsgemeinschaft, see also the FOR630 Homepage), the Volkswagenstiftung, CAPES, and the Fonds der Chemischen Industrie.

 

				Fonds der Chemischen Industrie

  

 

 

 

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Group / contact

		J.-Prof. Dr. Ingo Ott short CV    Email phone: +49 (0)531 391 2743 fax: +49 (0)531 391 8456
		Dr. Kely Navakoski de Oliveira postdoc Email  phone: +49 (0)531 391 7316
		Andreas Meyer, Pharmacist PhD student Email phone: +49 (0)531 391 8455
		Riccardo Rubbiani, Pharmacist PhD student Email phone: +49 (0)531 391 8455
		Luciano Oehninger, Chemist PhD student  Email phone: +49 (0)531 391 2778
		Julia Schur, Pharmacist PhD student Email phone: +49 (0)531 391 8458
		Vincent Andermark PhD student Email  phone: +49 (0)531 391 8458

 

 

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Jobs & internships

 

Positions for PhD students and Postdocs

 

At the moment all positions are filled.

New openings will be announced on this website as soon as available.

 

Postdoctoral candidates who want to apply for third-party funded fellowships are always welcome to contact us.

 

Internships for local students

 

Research training

Fundings are available for a limited number of (under)graduate students, who are interested in gaining early experience in research during the semester breaks or the "PJ". Minimum requirement for undergraduates is a good study performance in the chemical subjects of the first 4 semesters. Interested candidates are requested to contact any of the group members.

 

"Wahlpflichtfach"

Students performing this practical course in our group are integrated in ongoing research projects of the current PhD students. The training involves the synthetic preparation and / or biological evaluation of metal anticancer drugs. Get more information during the next "Nachmittag der Forschung".

 

 

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Publications

 

Research papers (for reviews and others click here )

·         Köster D. S., Alborzinia H., Can S., Kitanovic I., Wölfl S., Rubbiani R., Ott I., Riesterer P, Prokop A., Merz K., Metzler-Nolte N., A spontaneous gold(I)-azide alkyne cycloaddition reaction yields gold-peptide bioconjugates which overcome cisplatin resistance in a p53-mutant cancer cell line. Chem. Sci., accepted

·         Nazif M. A., Rubbiani R., Alborzinia H., Kitanovic I., Wölfl S., Ott I., Sheldrick W. S., Cytotoxicity and cellular impact of dinuclear organoiridium DNA  intercalators and nucleases with long rigid bridging ligands. Dalton Trans., accepted

·         Krüger M., Huang M., Becker-Roβ H., Fllorek S., Ott I., Gust R., Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry. Spectrochim. Acta, part B, accepted

·         Geldmacher Y., Splith K., Kitanovic I., Alborzinia H., Can S., Rubbiani R., Nazif M. A., Wefelmeyer P., Prokop A., Ott I., Wölfl S., Neundorf I., Sheldrick W. S., Cellular impact and selectivity of half-sandwich organorhodium(III) anticancer complexes and their organoiridium(III) and trichloridorhodium(III) counterparts. J. Biol. Inorg. Chem., accepted

·         Osowole A. A., Ott I., Ogunlana O. M., Synthesis, spectroscopic, anticancer, and antimicrobial properties of some metal(II) complexes of (substituted) nitrophenol schiff base. Int. J. Inorg. Chem. (2012), ID 206417.

·         Kasper C., Alborzinia H., Can S., Kitanovic I., Meyer A., Geldmacher Y., Oleszak M., Ott I., Wölfl S., Sheldrick W. S., Synthesis and cellular impact of diene–ruthenium(II) complexes: A new class of organoruthenium anticancer agents. J. Inorg. Biochem. (2012), 106, 126-133.

·         Rubbiani R., Can S., Kitanovic I., Alborzinia H., Stefanopoulou M., Kokoschka M., Mönchgesang S., Sheldrick W. S., Wölfl S., Ott I.*, Comparative in vitro evaluation of N-heterocyclic carbene gold(I) complexes of the benzimidazolylidene type. J. Med. Chem. (2011), 54, 8646-8657.

·         Gasser G., Neumann S., Ott I., Seitz M., Heumann R., Metzler-Nolte N. Preparation and biological evaluation of di-hetero organometallic-containing PNA bioconjugates. Eur. J. Inorg. Chem. (2011), 5471-5478.

·         Oehninger L., Alborzinia H., Ludewig S., Baumann K., Wölfl S., Ott I.*, From catalysts to bioactive organometallics: do Grubbs catalysts trigger biological effects ? ChemMedChem (2011), 6, 2142-2145.

·         Ott I.*, Xu Y., Qian X., Fluorescence properties and antiproliferative effects of mono-, bis-, and tris thiophenylnaphthalimides: results of a comparative pilot study. J. Photochem. Photobiol. B (2011), 105, 75-80.  

·         Wetzel C., Kunz P. C., Kassack M. U., Hamacher A., Böhler P., Wätjen W., Ott I., Rubbiani R., Spingler B., Gold(I) complexes of water-soluble diphos-type ligands: Synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition. Dalton Trans. (2011), 40, 9212-9220.

·         Tolle N., Dunkel U., Oehninger L., Ott I., Preu L., Haase T., Behrends S., Jones P. G., Totzke F., Schächtele C., Kubbutat M. H. G., Kunick C., Synthesis and Structure of Fluorescent Chelate Boron Complexes of 4-Anilinomethylidene-1-benzazepine-2,5-dione Ligands. Synthesis (2011), 17, 2848-2858.

·         Hackenberg F., Oehninger L., Alborzinia H., Can S., Kitanovic I., Geldmacher Y., Kokoschka M., Wölfl S., Ott I., Sheldrick W. S., Highly cytotoxic substitutionally inert rhodium(III) tris(chelate) complexes: DNA binding modes and biological impact on human cancer cells. J. Inorg. Biochem. (2011), 105, 991-999.

·         Bieda R., Kitanovic I., Alborzinia H., Meyer A., Ott I., Wölfl S., Sheldrick W. S., Antileukemic activity and cellular effects of rhodium(III) crown thiaether complexes. Biometals (2011), 24, 645-661.

·         Geldmacher Y., Rubbiani R., Wefelmeier P., Prokop A., Ott I., Sheldrick W. S., Synthesis and DNA-binding properties of apoptosis-inducing cytotoxic half-sandwich rhodium(III) complexes with methyl-substituted polypyridyl ligands, J. Organomet. Chem. (2011), 696, 1023-1031.

·         Geldmacher Y., Kitanovic I., Alborzinia H., Bergerhoff K., Rubbiani R., Wefelmeier P., Prokop A., Gust R., Ott I., Wölfl S., Sheldrick W.S., Cellular Selectivity and Biological Impact of Cytotoxic Rhodium(III) and Iridium(III) Complexes Containing Methyl-substituted Phenanthroline Ligands. ChemMedChem (2011), 6, 429-439.

·         Hille A., Wolf T., Schumacher P., Ott I., Gust R., Kircher B., Effects of metal salophene and saldach complexes on lymphoma and leukemia cells. Arch. Pharm. Chem. Life Sci. (2011), 11, 217-223.

·         Rubbiani R., Kitanovic I., Alborzinia H., Can S., Kitanovic A., Onambele L. A., Stefanopoulou M., Geldmacher Y., Sheldrick W. S., Wolber G., Prokop A., Wölfl S., Ott I.*, Benzimidazol-2-ylidene gold(I) complexes are thioredoxin reductase inhibitors with multiple antitumor properties. J. Med. Chem. (2010), 53, 8608-8618.

·         Rubner G., Bensdorf K., Wellner A., Bergemann S., Ott I., Gust R., [Cyclopentadienyl]metalcarbonyl complexes of acetylsalicylic acid as neo-anticancer agents. Eur. J. Med. Chem. (2010), 45, 5157-5163

·         Rubner G., Bensdorf K., Wellner A., Kircher B., Bergemann S., Ott I., Gust R., Synthesis and biological activities of transition metal complexes based on acetylsalicylic acid as neo-anticancer agents. J. Med. Chem. (2010), 53, 6889-6898

·         Bieda R., Dobroschke M., Triller A., Ott I., Spehr M., Gust R., Prokop A., Sheldrick W. S., Cell selective, apoptosis-inducing rhodium(III) crown thiaether complexes, ChemMedChem (2010), 5, 1123-1133.

·         Klein A., Lüning A., Ott I., Hamel L., Neugebauer M., Butsch K., Lingen V., Heinrich F., Elmas F., Organometallic palladium and platinum complexes with strongly donating alkyl coligands - synthesis, chemical structures and cytotoxic properties. J. Organomet. Chem. (2010), 695, 1898-1905.

·         Splith K., Hu W., Schatzschneider U., Gust R., Ott I., Onambele, L. A., Prokop A., Neundorf I. Protease-activatable organometal-peptide bioconjugates with enhanced cytotoxicity on cancer cells. Bioconjug. Chem. (2010), 21, 1288-1296.

·         Butsch K., Gust R., Klein A., Ott I., Romanski M., Tuning the electronic properties of dppz-ligands and their palladium(II) complexes. Dalton Trans. (2010), 39, 4331-4340.

·         Ott I.*, Kowalski K., Gust R., Maurer J., Mücke P., Winter R.F., Comparative biological evaluation of two ethylene linked mixed binuclear ferrocene / ruthenium organometallic species. Bioorg. Med. Chem. Lett. (2010), 20, 866-869.

·         Scheffler H., You Y., Ott I.*, Cytotoxicity, cellular and nuclear uptake of a series of chloro gold(I) phosphine complexes. Polyhedron (2010), 29, 66-69.

·         Bagowski C. P., You Y., Scheffler H., Vlecken D.H., Schmitz D. J., Ott I.*, Naphthalimide gold(I) phosphine complexes as anticancer metallodrugs. Dalton Trans. (2009), 10799-10805.

·         Bieda R., Ott I., Gust R., Sheldrick W.S.,Cytotoxic rhodium(III) polypyridyl complexes containing the tris(pyrazolyl)methane coligand: synthesis, DNA-binding properties and structure-activity relationships., Eur. J. Inorg. Chem. (2009), 25, 3821-3831.

·         Patra M., Gasser G., Pinto A., Merz K., Ott I., Bandow E. J., Metzler-Nolte N., Synthesis and biological evaluation of chromium bioorganometallics based on the antibotic platensimycin lead structure. ChemMedChem (2009), 4, 1930-1938.

·         Nazif A., Bangert J. A., Ott I., Gust R., Stoll R., Sheldrick W. S., Dinuclear organoiridium(III) mono- and bis-intercalators with rigid bridging ligands: synthesis, cytotoxicity and DNA-binding. J. Inorg. Biochem. (2009), 103, 1405-1414.

·         Walther C., Ott I., Gust R., Neundorf I., Specific labeling with potent radionuclides alters the uptake of cell-penetrating peptides, Biopolymers (2009), 92, 445-451.

·         Kappert K., Tsuprykov O., Kaufmann J., Fritzsche J., Ott I., Goebel M., Bahr I. N., Hassle P. L., Gust R., Fleck E., Unger T., Stawowy P., Kintscher U., Chronic treatment with losartan results in sufficient serum levels of the metabolite EXP3179 for PPARgamma activation. Hypertension (2009), 54, 738-743.

·         Butsch K., Elmas S., Gupta N. S., Gust R., Heinrich F., Klein A., von Mering Y., Neugebauer M., Ott I., Schäfer M., Scherer H., Schurr T., Organoplatinum(II) and -palladium(II) complexes of nucleobases and their derivatives. Organometallics (2009), 28, 3906-3915.

·         Hille A., Ott I., Kitanovic A., Kitanovic I., Alborzinia H., Lederer E., Wölfl S., Metzler-Nolte N., Schäfer S., Sheldrick W.S., Bischof C., Schatzschneider U., Gust R., [N, N'-Bis(salicylidene)-1,2-phenylenediamine] metal complexes with cell death promoting properties. J. Biol. Inorg. Chem. (2009), 14, 711-725.

·         Bieda R., Ott I., Dobroschke M., Prokop A., Gust R., Sheldrick W. S., Structure-activity relationships and DNA binding properties of apoptosis inducing rhodium(III) polypyridyl complexes containing the cyclic thioether [9]aneS₃. J. Inorg. Biochem. (2009), 103, 698-708.

·         N'Dongo H. W. P., Ott I., Gust R.,Schatzschneider U., Microwave-assisted solid-phase synthesis, cellular uptake, and cytotoxicity studies of cymantrene-peptide bioconjugates. J. Organomet. Chem. (2009), 694, 823-827.

·         Ott I.*, Qian X., Xu Y., Vlecken D. H., Marques I. J., Kubat D., Will J., Sheldrick W. S., Jesse P., Prokop A., Bagowski C. P., A gold(I) phosphine complex containing a naphthalimide ligand functions as a TrxR inhibiting antiproliferative agent and angiogenesis inhibitor. J. Med. Chem. (2009), 53, 763-770.

·         Ott I.*, Kircher B., Bagowski C. P., Vlecken D. H. W., Ott E. B., Will J., Bensdorf K., Sheldrick W. S., Gust R., Modulation of the biological properties of aspirin by bioorganometallic derivatisation. Angew. Chem. Int. Ed. (2009), 48, 1160-1163.

·         Sinning C., B. Watzer, Coste O., Nüsing R. M., Ott I., Ligresti A., Di Marzo V., Imming P., New analgesics synthetically derived from the paracetamol metabolite N-(4-hydroxyphenyl)-(5Z,8Z,11Z,14Z)-icosatetra-5,8,11,14-enamide. J. Med. Chem. (2008), 51, 7800-7805.

·         Schlenk M., Ott, Gust R., Cobalt-alkyne complexes with imidazoline ligands as estrogenic carriers. J. Med. Chem. (2008), 51, 7318-7322.

·         Ott I.*, Xu Y., Liu J., Kokoschka M., Harlos M., Sheldrick W.S., Qian X., Sulfur substituted naphthalimides as photoactivatable anticancer agents: DNA interaction, fluorescence imaging and phototoxic effects in cultured tumor cells. Bioorg. Med. Chem. (2008), 16, 1707-1716.

·         Schatzschneider U., Niesel J., Ott I., Gust R., Alborzinia H., Wölfl S., Cellular uptake, cytotoxicity and metabolic profiling, of human cancer cells treated with ruthenium(II) polypyridyl complexes. ChemMedChem (2008), 3, 1104-1109.

·         Scharwitz M. A., Ott I., Gust R., Kromm A., Sheldrick W.S., Synthesis, cellular uptake and structure-activity relationships for potent cytotoxic trichlorididoiridium(III) polypyridyl complexes. J. Inorg. Biochem. (2008), 102, 1623.

·         Harlos M., Ott I., Gust R., Alborzinia H., Wölfl S., Kromm A., Sheldrick W. S., Synthesis, biological activity and structure activity relationships for potent cytotoxic rhodium (III) polypyridyl complexes. J. Med. Chem. (2008), 51, 3924-3933.

·         Ott I.*, Scharwitz M., Scheffler H., Sheldrick W. S., Gust R., Atomic absorption spectrometric determination of the iridium content of tumor cells exposed to an iridium metallodrug. J. Pharm. Biomed. Anal. (2008), 47, 938-942.

·         Kirin S. I., Ott I, Gust R., Mier W., Weyhermüller T., Metzler-Nolte N., Cellular uptake quantification of metallated peptide and peptide nucleic acid bioconjugates by atomic absorption spectroscopy. Angew. Chem., Int. Ed. (2008), 47, 955-959.

·         Niesel J., Pinto A., Peindy N`Dongo H. W., Merz K., Ott I., Gust R., Schatzschneider U. Photoinduced CO-release, cellular uptake and cytotoxicity of a tris(pyrazolyl)methane (tpm) manganese tricarbonyl complex. Chem. Commun. (2008), 1798-1800.

·         Sergeant C. D., Ott I.*, Sniady A., Meneni, S., Gust R., Rheingold A. L., Dembinski R., Metallo-nucleosides: synthesis and biological evaluation of hexacarbonyl dicobalt 5-alkynyl-2'-deoxyuridines. Org. Biomol. Chem. (2008), 6, 73-80.

·         Kapp T., Krüger M., Ott I., Steiner S., Schumacher P., Nachbaur D., Gastl G., Gust R., Kircher B., Biological effect of mono- and dinuclear alkylamine platinum(II) compounds on human lymphoma cells. J. Inorg. Biochem. (2008), 102, 713-720.

·         Scharwitz M. A., Ott I., Geldmacher Y., Gust R., Sheldrick W.S. "Cytotoxic half-sandwich rhodium(III) complexes: polypyridyl ligand influence on their DNA binding properties and cellular uptake." J. Organomet. Chem. (2008), 693, 2299-2309.

·         Schäfer S., Ott I., Gust R., Sheldrick W. S., Influence of the polypyridyl (pp) ligand size on the DNA binding properties, cytotoxicity and cellular uptake of organoruthenium(II) complexes of the types [(Ti·⁶-C₆Me₆)Ru(L)(pp)]ⁿ⁺ (L=Cl, n=1; L= (NH₂)₂CS, n=2). Eur. J. Inorg. Chem. (2007), 3034-3046.

·         Ott I.*, Scheffler H., Gust R., Development of a method for the quantification of the molar gold concentration in tumor cells exposed to gold containing drugs. ChemMedChem (2007), 2, 702-707.

·         Meneni S., Ott I., Sergeant C.D., Sniady A., Gust R., Dembinski R., 5-Alkynyl-2-deoxyuridines: chromatography-free synthesis and cytotoxicity evaluation against human breast cancer. Bioorg. Med. Chem. (2007), 15, 3082-3088.

·         Banekovich C., Ott I.*, Koch T., Matuszczak B., Gust R., Synthesis and biological activities of novel dexibuprofen tetraacetylriboflavin conjugates. Bioorg. Med. Chem. Lett. (2007), 17, 683-687.

·         Ott I.*, Abraham A., Schumacher P., Shorafa H., Gastl G., Gust R., Kircher B., Synergistic and additive antiproliferative effects on human leukemia cell lines induced by combining acetylenehexacarbonyldicobalt complexes with the tyrosine kinase inhibitor imatinib. J. Inorg. Biochem. (2006), 100, 1903-1906.

·         Ott I., Kircher B., Schumacher P., Schmidt K., Gust R., Antitumoractive cobalt-alkyne complexes derived from acetylsalicylic acid: studies on the mode of drug action., J. Med. Chem. (2005), 48, 622-629.

·         Wiglenda T., Ott I., Kircher B., Schumacher P., Schuster D., Langer T., Gust R., Synthesis and pharmacological evaluation of 1H-imidazoles as ligands for the estrogen receptor and cytotoxic inhibitors of the cyclooxygenase. J. Med. Chem. (2005), 48, 6516-6521.

·         Ott I., Koch T., Shorafa H., Bai Z., Pöckel D., Steinhilber D., Gust R. Synthesis, cytotoxicity, cellular uptake and influence on eicosanoid metabolism of cobalt-alkyne modified fructoses in comparison to auranofin and the cytotoxic COX inhibitor Co-ASS. Org. Biomol. Chem. (2005), 3, 2282-2286.

·         Ott I., Gust R., Stability, protein binding and thiol interaction studies on [2-acetoxy-(2-propynyl)benzoate]hexacarbonyldicobalt., Biometals (2005), 18, 171-177.

·         Gust R., Ott I., Posselt D., Sommer K., Development of cobalt(3,4-diarylsalen)complexes as tumor therapeutics., J. Med. Chem. (2004), 47, 5837-5846.

·         Ott I., Kircher B., Heinisch G., Matuszczak B., Substituted pyridazino[3,4-b][1,5]benzoxazepin-5(6H)ones as multidrug resistance modulating agents., J. Med. Chem. (2004), 47, 4627-4630.

·         Ott I., Kircher B., Gust R., Investigations on the effects of cobalt-alkyne complexes on leukemia and lymphoma cells: cytotoxicity and cellular uptake., J. Inorg. Biochem. (2004), 98, 485-489.

·         Amann A., Decristoforo C., Ott I., Wenger M., Bader D., Alberto R., Putz G., Surfactant protein B labelled with [^99mTc(CO)₃(H₂O)₃]⁺ retains biological activity in vitro., Nucl. Med. Biol. (2001), 28, 243-250.

 

Reviews and other contributions in journals

·         Gasser G., Ott I., Metzler-Nolte N., Organometallic Anticancer Compounds, J. Med. Chem. (2011), 54,3-25

·         Ott I.*, Kunick C., Metal complexes as protein kinase inhibitors. Angew. Chem. Int. Ed. (2010), 49, 5226-5227.

·         Ott I.*, Metalle: Bausteine für Wirkstoffe. Nachrichten aus der Chemie (2009), 57, 628-631.

·         Ott I.*, On the medicinal chemistry of gold complexes as anticancer drugs. Coord. Chem. Rev. (2009), 253, 1670-1681.

·         Ott I.*, Kircher B., Dembinski R., Gust R. Alkyne hexacarbonyl dicobalt complexes in medicinal chemistry and drug development. Expert Opin. Therap. Patents (2008), 18, 327-337.

·         Ott I.*, Gust R., Organometallverbindungen: Hilfreich in der Therapie von Tumorerkrankungen. Pharmazeutische Zeitung (2007), 32, 74-76.

·         Ott I.*, Gust R., Non platinum metal complexes as anti-cancer agents. Arch. Pharm. Chem. Life Sci. (2007), 340, 117-126.

·         Ott I., Gust R., Preclinical and clinical studies on the use of platinum complexes for breast cancer treatment. Anti-Cancer Agents in Medicinal Chemistry (2007), 7, 95-110.

·         Ott I., Gust R., Medizinische Chemie der Platinkomplexe. Pharm. Unserer Zeit (2006), 35, 124-133.

 

 Patents

·         Gust R., Ott I., Sheldrick W. S., Harlos M. Octahedral metal(III) polypyridyl complexes and their use in prevention and treatment of cancer. EP2072521 (A1), WO2009080482 (A1)

 

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