zur Suche springenzur Navigation springenzum Inhalt springen

Publikationen - Natur- und Wirkstoffchemie

Sortieren nach: Erscheinungsjahr Typ der Publikation

Zeige Ergebnisse 1 bis 10 von 12.

Publikation

Edeler, D.; Drača, D.; Petković, V.; Natalio, F.; Maksimović-Ivanić, D.; Mijatović, S.; Schmidt, H.; Kaluđerović, G. N.; Impact of the mesoporous silica SBA-15 functionalization on the mode of action of Ph3Sn(CH2)6OH Mater. Sci. Eng. C-Mater. Biol. Appl. 100, 315-322, (2019) DOI: 10.1016/j.msec.2019.03.010

Herein appropriateness of nonfunctionalized mesoporous silica nanoparticles SBA-15 and functionalized with (3-chloropropyl)triethoxysilane (→ SBA-15~Cl) and (3-aminopropyl)triethoxysilane (→ SBA-15~NH2) on delivery of physically adsorbed Ph3Sn(CH2)6OH (Sn6) is evaluated. Fluorescent nanomaterial, bearing isatoic moiety, loaded with Sn6 (→ SBA-15~NF|Sn6) was used for cellular uptake study. The fluorescent nanomaterial is efficiently acquired and distributed into the cytoplasm of the cells even after 2 h of cultivation. According to the attained data, all SBA-15 materials loaded with Sn6 diminished cellular viability in dose dependent manner while carriers alone (SBA-15, SBA-15~Cl, SBA-15~NH2) did not show cytotoxicity against B16 cells. According to the MC50 values structural modification of SBA-15 did not improve the efficacy of tested drug. While progressive apoptosis was detected upon the treatment with SBA-15|Sn6, exposure of cells to SBA-15~NH2|Sn6 revealed extinguished apoptosis in time, accompanied with lower caspase activity. This effect is probably due to triggered autophagic process under the treatment with the SBA-15~NH2|Sn6, thus opposed to apoptosis. Presented results suggested that functionalization of SBA-15 was not beneficial for the efficacy of loaded drug, thus, all of them are almost equally efficient considering loaded Sn6 content. Importantly, functionalization of SBA-15 does have an influence on the mode of action and differentiation inducing properties.
Publikation

Walther, T.; Herzog, R.; Kaluđerović, M. R.; Wagner, C.; Schmidt, H.; Kaluđerović, G. N.; Traceable platinum(II) complexes with alkylene diamine-derived ligands: synthesis, characterization and in vitro studies J. Coord. Chem. 71, 243-257, (2018) DOI: 10.1080/00958972.2018.1431392

Diiodido- (6a/6b) and dichloridoplatinum(II) complexes (7a/7b) with fluorescent ligands 2-[(2-aminoethyl)amino]ethyl-2-(methylamino)benzoate (5a) and 2-amino-1-(aminoethyl)ethyl-2-(methylamino)benzoate (5b) were prepared and characterized by elemental analysis, ESI-MS analysis, fluorescence spectrometry, as well as 1H, 13C, and 195Pt NMR spectroscopy. All compounds have been tested against A2780 ovarian cancer, A549 lung carcinoma, and HT-29 colon cancer cell lines using sulforhodamine-B assay. The activity increased from ligand precursors, diiodido- to dichloridoplatinum(II) complexes, except against HT-29 cell line where diiodido and dichlorido expressed similar activity. These compounds enter the tumor cells and emit a bright fluorescence at ca. 470 nm, mainly targeting nuclei.
Publikation

Edeler, D.; Bensing, C.; Schmidt, H.; Kaluđerović, G. N.; Preparation and in vitro investigations of triphenyl[ω-(tetrahydro-2H-pyran-2-yloxy)alkyl]tin(IV) compounds Appl. Organomet. Chem. 31, e3630, (2017) DOI: 10.1002/aoc.3630

The reaction of SnPh3Li with X(CH2)nO–THP (THP = tetrahydro‐2H‐pyran‐2‐yl; n = 3, 4, 6, 8, 11; X = Cl, Br) afforded organotin(IV) compounds with the general formula Ph3Sn(CH2)nO–THP (1–5). The tetraorganotin(IV) compounds were characterized using multinuclear NMR and infrared spectroscopies and high‐resolution mass spectrometry. Anticancer activity of the synthesized compounds was tested in vitro against the A2780 (ovarian), A549 (lung), HeLa (adenocarcinoma) and SW480 (colon) tumour cell lines with SRB assay. The in vitro investigations revealed that when a shorter chain was present a higher activity was achieved; however compounds 1–5 were found to be less active than cisplatin. In addition, the most active compound, 1, enters A2780 cells and causes apoptosis by triggering both intrinsic and extrinsic caspase pathways.
Publikation

Edeler, D.; Kaluđerović, M. R.; Dojčinović, B.; Schmidt, H.; Kaluđerović, G. N.; SBA-15 mesoporous silica particles loaded with cisplatin induce senescence in B16F10 cells RSC Adv. 6, 111031-111040, (2016) DOI: 10.1039/C6RA22596A

The anticancer drug cisplatin (CP) is loaded into SBA-15 mesoporous silica (SBA-15|CP) and its release from the nanomaterial is studied. The CP-loaded SBA-15 is tested against four tumor cell lines: mouse malignant melanoma B16F10, human adenocarcinoma HeLa, colon HT-29 and prostate PC3. Most importantly, the superiority of this novel material in comparison to CP arises from the fact that the CP-grafted nanomaterial SBA-15 (→SBA-15|CP) is enhancing cessation of proliferation along with induction of senescence in B16F10 in approximately 3.5 times lower concentration. The control material loaded with therapeutically inactive K2[PtCl4] (→SBA-15|TC) showed no antitumor activity. To a large extent, SBA-15|CP-induced senescence might present a safe approach in tumor treatment. Such cells can be cleared by immune cells resulting in efficient tumor regression. So far only apoptotic agents are being exploited in clinics, thus an understanding of the chemotherapeutic-induced senescence will allow oncologists to explore this essential tumor suppressor mechanism.
Publikation

Momčilović, M.; Eichhorn, T.; Blazevski, J.; Schmidt, H.; Kaluđerović, G. N.; Stosic-Grujicic, S.; In vitro effects of binuclear (η6-p-cymene)ruthenium(II) complex containing bridging bis(nicotinate)-polyethylene glycol ester ligand on differentiation pathways of murine Th lymphocytes activated by T cell mitogen J. Biol. Inorg. Chem. 20, 575-583, (2015) DOI: 10.1007/s00775-015-1242-x

T cell differentiation into distinct T helper (Th) subpopulations is crucial in governing acquired immune responses as well as some inflammatory and autoimmune disorders. This study investigated potential of the novel neutral binuclear ruthenium(II) complexes 1–8 with general formula [{RuCl2(η6-p-cym)}2μ-(N∩N)] (N∩N = bis(nicotinate)- and bis(iso-nicotinate)-polyethylene glycol esters; (3-py)COO(CH2CH2O) n CO(3-py) and (4-py)COO(CH2CH2O) n CO(4-py); n = 1–4), as well as [RuCl2(η6-p-cym)(nic)] (R1, nic = nicotinate) and [RuCl2(η6-p-cym)(inic)] (R2, inic = isonicotinate) as an immunomodulatory agents capable to direct Th cell differentiation. From all investigated complexes, [{RuCl2(η6-p-cym)}2μ-{(3-py)COO(CH2CH2O)4CO(3-py)}] (4) was selected for further study because it did not affect splenocyte viability (in concentration up to 50 μM), but significantly reduced secretion of representative Th1 cytokine, IFN-γ induced by T cell mitogen. Besides IFN-γ, 4 inhibited dose dependently expression and production of representative Th17 cytokine, IL-17, in these cells. Otherwise, the production of anti-inflammatory cytokines IL-4 and IL-10 was upregulated. Also, 4 significantly increased CD4+CD25+FoxP3+ Treg cell frequency in the activated splenocytes. Moreover, ConA-induced expression of Th1 transcription factors, T-bet and STAT1, as well as of Th17-related protein STAT3 was attenuated upon exposure to 4, while the expression of Th2-related transcription factor GATA3 remained stable. In conclusion, ruthenium(II) complex 4 modulates immune system cell functions in vitro by inhibiting T cell differentiation towards pathogenic Th1/Th17 phenotype and inducing a regulatory phenotype characterized by IL-10 and IL-4 production, which may provide novel therapeutic opportunities for immune-inflammatory and/or autoimmune disorders.
Publikation

Eichhorn, T.; Hey-Hawkins, E.; Maksimović-Ivanić, D.; Mojić, M.; Schmidt, J.; Mijatović, S.; Schmidt, H.; Kaluđerović, G. N.; Binuclear dichlorido(η6-p-cymene)ruthenium(II) complexes with bis(nicotinate)- and bis(isonicotinate)-polyethylene glycol ester ligands Appl. Organomet. Chem. 29, 20-25, (2015) DOI: 10.1002/aoc.3238

Neutral binuclear ruthenium complexes 1, 2, 3, 4, 5, 6, 7, 8 of the general formula [{RuCl2(η6‐p‐cym)}2 μ‐(N∩N)] (N∩N = bis(nicotinate)‐ and bis(isonicotinate)‐polyethylene glycol esters: (3‐py)COO(CH2CH2O)nCO(3‐py) and (4‐py)COO(CH2CH2O)nCO(4‐py), n =1–4), as well as mononuclear [RuCl2(η6‐p‐cym)((3‐py)COO(CH2CH2OCH3)‐κN)], complex 9, were synthesized and characterized using elemental analysis and electrospray ionization high‐resolution mass spectrometry, infrared, 1H NMR and 13C NMR spectroscopies. Stability of the binuclear complexes in the presence of dimethylsulfoxide was studied. Furthermore, formation of a cationic complex containing bridging pyridine‐based bidentate ligand was monitored using 1H NMR spectroscopy. Ligand precursors, polyethylene glycol esters of nicotinic (L1 · 2HCl–L4 · 2HCl and L9 · HCl) and isonicotinic acid dihydrochlorides (L5 · 2HCl–L8 · 2HCl), binuclear ruthenium(II) complexes 1, 2, 3, 4, 5, 6, 7, 8 and mononuclear complex 9 were tested for in vitro cytotoxicity against 518A2 (melanoma), 8505C (anaplastic thyroid cancer), A253 (head and neck tumour), MCF‐7 (breast tumour) and SW480 (colon carcinoma) cell lines.
Publikation

Bulatović, M. Z.; Maksimović-Ivanić, D.; Bensing, C.; Gómez-Ruiz, S.; Steinborn, D.; Schmidt, H.; Mojić, M.; Korać, A.; Golić, I.; Pérez-Quintanilla, D.; Momčilović, M.; Mijatović, S.; Kaluđerović, G. N.; Organozinn(IV)-beladenes mesoporöses SiO2 als biokompatible Strategie bei der Krebstherapie Angew. Chem. 126, 6092-6097, (2014) DOI: 10.1002/ange.201400763

Das große therapeutische Potenzial eines Organozinn(IV)‐beladenen nanostrukturierten SiO2 (SBA‐15pSn) wird am Beispiel der Rückbildung eines durch B16‐Zellen induzierten Melanoms bei syngenen C57BL/6‐Mäusen demonstriert. Neben Apoptose als grundlegendem Mechanismus der Antitumorwirkung einer Vielzahl von Chemotherapeutika ist der entscheidende Vorteil dieses mesoporösen zinnhaltigen Materials das Auslösen der Zelldifferenzierung – ein Effekt, der weder für metallbasierte Zytostatika noch für mesoporöse Materialien alleine bisher beobachtet wurde. Dieser nichtaggressive Wirkungsmechanismus ist hochwirksam gegen Tumorzellen aber im gewählten Konzentrationsbereich nichttoxisch für normales Gewebe. JNK‐unabhängige Apoptose (JNK: Jun amino‐terminal kinase), begleitet von der Bildung des melanozytenartigen nichtproliferativen Phänotyps der überlebenden Zellen demonstriert das außergewöhnliche Potenzial von SBA‐15pSn zur Unterdrückung von Tumorwachstum ohne eine unerwünschte kompensatorische Proliferation der erkrankten Zellen als Antwort auf den Zelltod in ihrer Nachbarschaft.
Publikation

Bulatović, M. Z.; Maksimović-Ivanić, D.; Bensing, C.; Gómez-Ruiz, S.; Steinborn, D.; Schmidt, H.; Mojić, M.; Korać, A.; Golić, I.; Pérez-Quintanilla, D.; Momčilović, M.; Mijatović, S.; Kaluđerović, G. N.; Organotin(IV)-Loaded Mesoporous Silica as a Biocompatible Strategy in Cancer Treatment Angew. Chem. Int. Ed. 53, 5982-5987, (2014) DOI: 10.1002/anie.201400763

The strong therapeutic potential of an organotin(IV) compound loaded in nanostructured silica (SBA‐15pSn) is demonstrated: B16 melanoma tumor growth in syngeneic C57BL/6 mice is almost completely abolished. In contrast to apoptosis as the basic mechanism of the anticancer action of numerous chemotherapeutics, the important advantage of this SBA‐15pSn mesoporous material is the induction of cell differentiation, an effect unknown for metal‐based drugs and nanomaterials alone. This non‐aggressive mode of drug action is highly efficient against cancer cells but is in the concentration range used nontoxic for normal tissue. JNK (Jun‐amino‐terminal kinase)‐independent apoptosis accompanied by the development of the melanocyte‐like nonproliferative phenotype of survived cells indicates the extraordinary potential of SBA‐15pSn to suppress tumor growth without undesirable compensatory proliferation of malignant cells in response to neighboring cell death.
Publikation

Chaudhuri, S. R.; Kaluđerović, G. N.; Bette, M.; Schmidt, J.; Schmidt, H.; Paschke, R.; Steinborn, D.; Synthesis, characterization and cytotoxicity studies of platinum(II) complexes with amino acid ligands in various coordination modes Inorg. Chim. Acta 394, 472-480, (2013) DOI: 10.1016/j.ica.2012.08.034

Reactions of [Pt(CO3)(PPh3)2]·CH2Cl2 (1) with non-substituted and alkyl substituted amino acids, NH(R)CH(R′)CO2H (R/R′ = H/Me, L1; H/iPr, L2; H/CH2CHMe2, L3; Me/H, L4; Et/H, L5), in the presence of Tl[PF6] in methanol afforded with liberation of CO2 the formation of platinum(II) complexes of the type [Pt(PPh3)2{NHR–CHR′–C(O)O-κN,κO}][PF6] (R/R′ = H/Me, 2; H/iPr, 3; H/CH2CHMe2, 4; Me/H, 5; Et/H, 6). Single-crystal X-ray diffraction analysis of complex 4 exhibited a square-planar coordination of the platinum atom having coordinated two triphenylphosphane ligands and a deprotonated κN,κO-coordinated leucine ligand (L3−H). On varying the pKa value of the amino group, platinum(II) complexes with different coordination modes of amino acid ligands were obtained. Thus, treatment of complex 1 with N-acetyl l-alanine (L6), possessing a comparatively highly acidic NH proton, in 1:1 ratio in methanol resulted in the formation of [Pt(PPh3)2{N(COMe)–CHMe–C(O)O-κN,κO}] (7), while reacting N-phenyl glycine (L7) having a moderately acidic NH proton with complex 1 afforded a mixture of complexes [Pt(PPh3)2{NPh–CH2–C(O)O-κN,κO}] (8) and [Pt(PPh3)2{NHPh–CH2–C(O)O-κO}2] (10). Treatment of complex 1 with two equivalents of L6/L7 in dichloromethane resulted in the formation of [Pt(PPh3)2{NHR–CHR′–C(O)O-κO}2] (R/R′ = COMe/Me, 9; Ph/H, 10). An analogous reactivity was observed for l-lactic acid on treating with complex 1 in 1:1 and 2:1 ratio resulting in [Pt(PPh3)2{O–CHMe–C(O)O-κO,κO′}] (11) and [Pt(PPh3)2{HO–CHMe–C(O)O-κO}2] (12). The identities of all complexes have been proven by NMR (1H, 13C, 31P) spectroscopic and high-resolution ESI mass-spectrometric investigations. In vitro cytotoxicity studies against human tumor cell lines (8505C, A2780, HeLa, SW480, and MCF-7) showed the highest activities for the neutral complex 7. Furthermore, complexes 7 and 9 against the A2780 cell line induced an apoptotic mode of cell death, which was further supported by morphological investigation and DNA laddering. Cell cycle perturbation studies showed that both complexes induced faster cell death than cisplatin.
Publikation

Mihály, T.; Bette, M.; Mihály, B.; Schmidt, J.; Schmidt, H.; Steinborn, D.; Synthesis, structure and characterization of adenine-based aminocarbene complexes of platinum(II) J. Organomet. Chem. 739, 57-62, (2013) DOI: 10.1016/j.jorganchem.2013.04.030

The reaction of the dinuclear platina-β-diketone [Pt2{(COMe)2H}2(μ-Cl)2] (1) with two equivalents of adenine and its methylated derivatives N6-R,9-R′Ade–H resulted in adenine-based aminocarbene platinum(II) complexes [Pt(COMe)Cl{CMe(N6-R,9-R′Ade–H)-κC,κN}] (R/R′ = Me/Me, 2; H/Me, 3; H/H, 4) whose identities were confirmed by NMR and IR spectroscopies as well as by high-resolution mass spectrometric investigations. Single-crystal X-ray diffraction analyses of complexes 2 and 4·THF revealed relatively short Pt–C and N–C bonds in the aminocarbene–platinum units, which is in accord with a substantial double bond character of these bonds. The electronic structure of these complexes will be further confirmed by DFT calculations as also the course of reaction.
IPB Mainnav Search