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The anticancer activity of titanium complexes has been known since the groundbreaking studies of Köpf and Köpf-Maier on titanocen dichloride. Unfortunately, possibly due to their fast hydrolysis, derivatives of titanocen dichloride failed in clinical studies. Recently, the new family of titanium salan complexes containing tetradentate ONNO ligands with anti-cancer properties has been discovered. These salan complexes are much more stabile in aqueous media. In this study we describe the biological activity of two titanium salan complexes in a mouse model of cervical cancer. High efficiency of this promising complex family was demonstrated for the first time in vivo. From these data we conclude that titanium salan complexes display very strong antitumor properties exhibiting only minor side effects. Our results may influence the chemotherapy with metallo therapeutics in the future.
Leurs, Ulrike ; Mezo, Gabor ; Öhlschläger, Peter ; Orban, Erika ; Marquard, Andrea ; Manea, Marilena
Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.
Manea, Marilena ; Leurs, Ulrike ; Orban, Erika ; Baranyai, Zsuzsa ; Öhlschläger, Peter ; Marquardt, Andreas ; Schulcz, Akos ; Tejeda, Miguel
Öhlschläger, Peter ; Quetting, Michael ; Alvarez, Gerardo ; Dürst, Matthias ; Gissmann, Lutz ; Kaufmann, Andreas M.
Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7
(2011)
Oosterhuis, Koen ; Öhlschläger, Peter ; Berg, Joost H. van den ; Toebes, Mireille ; Gomez, Raquel ; Schumacher, Ton N. ; Haanen, John B.
Aggarwal, Pranav ; Dhiman, Shashi K. ; Kumar, G. ; Scherer, Ulrich W. ; Singla, M. L. ; Srivastava, Alok
Thin films of poly(ethyleneterephthalate) [PET]were exposed to radiation dose ranging from 10 to 30 kGy by using gamma rays in the range 12.8-177.8 MGy using swift light ions of hydrogen. There was no effect of the radiation dose on the optical behaviour of PET as a result of exposure to radiation dose up to 30 kGy brought about by gamma rays but a significant decrease in the optical band gap values was observed when PET was exposed to swift light ions of hydrogen. The data obtained are discussed in terms of optical studies carried out on PET using swift heavy ions.
Aggarwal, Prerna ; Singh, Virendra ; Singh, Arjun ; Scherer, Ulrich W. ; Singh, Tejvir ; Singla, Madan L. ; Srivastava, Alok
Bäcker, Matthias ; Delle, L. ; Poghossian, Arshak ; Biselli, Manfred ; Zang, Werner ; Wagner, P. ; Schöning, Michael Josef
Srivastava, Alok ; Singh, Virendra ; Aggarwal, Pranav ; Schneeweiss, F. ; Scherer, Ulrich W. ; Friedrich, W.
Martins, Berta M. ; Blaser, Martin ; Feliks, Mikolaj ; Ullmann, Matthias G. ; Buckel, Wolfgang ; Selmer, Thorsten
Werner, Frederik ; Groebel, Simone ; Wagner, Torsten ; Yoshinobu, Tatsuo ; Selmer, Thorsten ; Baumann, Marcus ; Schöning, Michael Josef
Biselli, Manfred ; Bäcker, Matthias ; Poghossian, Arshak ; Schöning, Michael Josef ; Schnitzler, Thomas ; Zang, Werner ; Wagner, P.
Werner, Frederik ; Krumbe, Christoph ; Schumacher, Katharina ; Groebel, Simone ; Spelthahn, Heiko ; Stellberg, Michael ; Wagner, Torsten ; Yoshinobu, Tatsuo ; Selmer, Thorsten ; Keusgen, Michael ; Baumann, Marcus ; Schöning, Michael Josef
Helle Fensterprofilmaterialien : Alterungsverhalten auf Basis von peroxidisch vernetztem EPDM
(2010)
Kowollik, S. ; Schnitzler, Thomas ; Biselli, Manfred ; Krueger, R. ; Zang, Werner ; Peuscher, A. ; Schillberg, S. ; Fischer, R.
Denk- und Lernspielzeug : Offenlegungsschrift : DE 102006003433 A1 ; Offenlegungstag: 26.07.2007
(2007)
Comparison of Intravenous Immunoglobulins for Naturally Occurring Autoantibodies against Amyloid-β
(2010)
Balakrishnan, Karthikeyan ; Andrei-Selmer, Luminita-Cornelia ; Selmer, Thorsten ; Bacher, Michael ; Dodel, Richard
Bestimmung der metabolischen Aktivität von Mikroorganismen während des Biogasbildungsprozesses
(2009)
Werner, Frederik ; Groebel, Simone ; Schuhmacher, K. ; Spelthahn, Heiko ; Wagner, Torsten ; Selmer, Thorsten ; Baumann, Marcus ; Schöning, Michael Josef
Bäcker, Matthias ; Beging, Stefan ; Biselli, Manfred ; Poghossian, Arshak ; Wang, J. ; Zang, Werner ; Wagner, Patrick ; Schöning, Michael Josef