المؤلفون: Anna Makowska, Franciszek Sączewski, Patrick J. Bednarski, Maria Gdaniec, Łukasz Balewski, Magdalena Warmbier, Anita Kornicka

المصدر: Molecules; Volume 27; Issue 21; Pages: 7155

مصطلحات موضوعية: Benzoxazoles, Triazines, Organic Chemistry, Pharmaceutical Science, 2-iminocoumarins, 2-imino-2H-chromene, 2H-chromen-2-imines, 1,3,5-triazines, benzoxazoles, benzothiazoles, copper(II) complexes, X-ray analysis, in vitro cytotoxic activity, Antineoplastic Agents, Crystallography, X-Ray, Ligands, Analytical Chemistry, Chemistry (miscellaneous), Coordination Complexes, Cell Line, Tumor, Drug Discovery, Molecular Medicine, Humans, Benzothiazoles, Imines, Physical and Theoretical Chemistry, Copper

الوصف: A series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h, 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b, and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c were obtained by reacting of appropriate 2-iminocoumarin ligands L1a-h, L3a-b, and L5a-c with 3-fold molar excess of copper(II) chloride. The structure of these compounds was confirmed by IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction data (2f, 2g, 2h, and 6c). All the synthesized complexes were screened for their activity against five human cancer cell lines: DAN-G, A-427, LCLC-103H, SISO, and RT-4 by using a crystal violet microtiter plate assay and relationships between structure and in vitro cytotoxic activity are discussed. The coordination of 2-iminocoumarins with copper(II) ions resulted in complexes 2a-h, 4a-b, and 6a-c with significant inhibitory properties toward tested tumor cell lines with IC50 values ranging from 0.04 μM to 15.66 μM. In comparison to the free ligands L1a-h, L3a-b, and L5a-c, the newly prepared Cu(II) complexes often displayed increased activity. In the series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h the most potent compound 2g contained a 4-phenylpiperazine moiety at position 6 of the 1,3,5-triazine ring and an electron-donating diethylamino group at position 7′ of the 2-iminocoumarin scaffold. Among the Cu(II) complexes of 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c the most active was benzoxazole-2-iminocoumarin 4b that also possessed a diethylamino group at position 7′ of the 2-iminocoumarin moiety. Moreover, compound 4b was found to be the most prominent agent and displayed the higher potency than cisplatin against tested cell lines.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c3a5d5d2eaa82a3868668b1787929cadTest

المؤلفون: Lisa Wolff, Siva Sankar Murthy Bandaru, Elias Eger, Hoai-Nhi Lam, Martin Napierkowski, Daniel Baecker, Carola Schulzke, Patrick J. Bednarski

المصدر: International Journal of Molecular Sciences
Volume 22
Issue 14
International Journal of Molecular Sciences, Vol 22, Iss 7631, p 7631 (2021)

مصطلحات موضوعية: reactive oxygen species, pentathiepin, Molecular Structure, QH301-705.5, Antineoplastic Agents, Apoptosis, Glutathione, Article, Chemistry, Oxidative Stress, Structure-Activity Relationship, Glutathione Peroxidase GPX1, Cell Line, Tumor, sulfur, cancer cells, Humans, cytotoxicity, DNA damage, Biology (General), Thiepins, glutathione peroxidase, QD1-999, Cell Proliferation

الوصف: Pentathiepins are polysulfur-containing compounds that exert antiproliferative and cytotoxic activity in cancer cells, induce oxidative stress and apoptosis, and inhibit glutathione peroxidase (GPx1). This renders them promising candidates for anticancer drug development. However, the biological effects and how they intertwine have not yet been systematically assessed in diverse cancer cell lines. In this study, six novel pentathiepins were synthesized to suit particular requirements such as fluorescent properties or improved water solubility. Structural elucidation by X-ray crystallography was successful for three derivatives. All six underwent extensive biological evaluation in 14 human cancer cell lines. These studies included investigating the inhibition of GPx1 and cell proliferation, cytotoxicity, and the induction of ROS and DNA strand breaks. Furthermore, selected hallmarks of apoptosis and the impact on cell cycle progression were studied. All six pentathiepins exerted high cytotoxic and antiproliferative activity, while five also strongly inhibited GPx1. There is a clear connection between the potential to provoke oxidative stress and damage to DNA in the form of single- and double-strand breaks. Additionally, these studies support apoptosis but not ferroptosis as the mechanism of cell death in some of the cell lines. As the various pentathiepins give rise to different biological responses, modulation of the biological effects depends on the distinct chemical structures fused to the sulfur ring. This may allow for an optimization of the anticancer activity of pentathiepins in the future.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::a7d2a658a7aaf555df3e4e6858275624Test

المؤلفون: Solomon Tesfaye, Hannah Braun, Kaleab Asres, Ephrem Engidawork, Anteneh Belete, Ilias Muhammad, Christian Schulze, Nadin Schultze, Sebastian Guenther, Patrick J. Bednarski

المصدر: Molecules
Molecules, Vol 26, Iss 3658, p 3658 (2021)

مصطلحات موضوعية: Plants, Medicinal, Plant Extracts, extractions, Organic chemistry, Antineoplastic Agents, Antineoplastic Agents, Phytogenic, Article, Inhibitory Concentration 50, QD241-441, Cell Line, Tumor, Humans, cytotoxicity, cancer, Ethiopia, Medicine, African Traditional, medicinal plants

الوصف: Medicinal plants have been traditionally used to treat cancer in Ethiopia. However, very few studies have reported the in vitro anticancer activities of medicinal plants that are collected from different agro-ecological zones of Ethiopia. Hence, the main aim of this study was to screen the cytotoxic activities of 80% methanol extracts of 22 plants against human peripheral blood mononuclear cells (PBMCs), as well as human breast (MCF-7), lung (A427), bladder (RT-4), and cervical (SiSo) cancer cell lines. Active extracts were further screened against human large cell lung carcinoma (LCLC-103H), pancreatic cancer (DAN-G), ovarian cancer (A2780), and squamous cell carcinoma of the esophagus (KYSE-70) by using the crystal violet cell proliferation assay, while the vitality of the acute myeloid leukemia (HL-60) and histiocytic lymphoma (U-937) cell lines was monitored in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) microtiter assay. Euphorbia schimperiana, Acokanthera schimperi, Kniphofia foliosa, and Kalanchoe petitiana exhibited potent antiproliferative activity against A427, RT-4, MCF-7, and SiSo cell lines, with IC50 values ranging from 1.85 ± 0.44 to 17.8 ± 2.31 µg/mL. Furthermore, these four extracts also showed potent antiproliferative activities against LCLC-103H, DAN-G, A2780, KYSE-70, HL-60, and U-937 cell lines, with IC50 values ranging from 0.086 to 27.06 ± 10.8 µg/mL. Hence, further studies focusing on bio-assay-guided isolation and structural elucidation of active cytotoxic compounds from these plants are warranted.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::a6534f319759ceadee5ae7819a95640dTest
http://europepmc.org/articles/PMC8232819Test

المؤلفون: Florence N, Mbaoji, Steven, Behnisch-Cornwell, Adaobi C, Ezike, Chukwuemeka S, Nworu, Patrick J, Bednarski

المصدر: Molecules

مصطلحات موضوعية: HepG2, SiSo, leaf, Plant Extracts, Anacardiaceae, stem bark, KYSE 70, Antineoplastic Agents, Lannea barteri, Cell Cycle Checkpoints, Hep G2 Cells, Antioxidants, Article, Plant Leaves, adherent human carcinoma cell lines, Neoplasms, Plant Bark, Humans, Cell Proliferation

الوصف: In western Africa ethnomedicine, Lannea barteri Oliv. (Anacardiaceae) is believed to have activity against gastrointestinal, neurological and endocrine diseases. Previous studies on this plant have revealed antimicrobial, anticholinestrase, anticonvulsant, antioxidant and anti-inflammatory activities. However, the anticancer potential of L. barteri has not been studied to date. The aim of this study was to evaluate the anticancer potential of hot and cold extracts and silica gel column chromatographic fractions of L. barteri leaf and stem bark. The extracts and fractions were tested for anticancer activity by using the crystal violet cell proliferation assay on four adherent human carcinoma cell lines—5637 (bladder), KYSE 70 (oesophagus), SiSo (cervical) and HepG2 (hepatic). The inhibitory concentration (IC50) of fractions IH, 1I, 2E and 2F were: 3.75 ± 1.33, 3.88 ± 2.15, 0.53 ± 0.41, and 0.42 ± 0.45 µg/mL against KYSE 70 and 1.04 ± 0.94, 2.69 ± 1.17, 2.38 ± 3.64, 2.17 ± 1.92 µg/mL against SiSo cell lines respectively. Fraction 2E showed weak apoptotic activity at double the IC50 and some sign of cell cycle arrest in the G2/M phase. Thus, phytoconstituents of L. barteri leaf and stem bark can inhibit the proliferation of cancer cell lines indicating the presence of possible anticancer agents in this plant.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::f8dd2c48fbd14f19130bb0705acd7721Test
https://pubmed.ncbi.nlm.nih.gov/32075139Test

المؤلفون: Łukasz Balewski, Anna Makowska, Patrick J. Bednarski, Franciszek Sączewski, Jarosław Sączewski

المصدر: Molecules
Volume 23
Issue 7
Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
Molecules, Vol 23, Iss 7, p 1616 (2018)

مصطلحات موضوعية: Acetonitriles, in vitro anticancer activity, Cell Survival, Pharmaceutical Science, Antineoplastic Agents, hybrid molecules, 2-imino-2H-chromen-3-yl-1,3,5-triazines, 01 natural sciences, Medicinal chemistry, Article, Analytical Chemistry, lcsh:QD241-441, Structure-Activity Relationship, lcsh:Organic chemistry, Cell Line, Tumor, Drug Discovery, Molecule, Cytotoxic T cell, Humans, Physical and Theoretical Chemistry, 2H-chromen-3-yl-1,3,5-triazines, Cell Proliferation, Aqueous solution, coumarins, Molecular Structure, 010405 organic chemistry, Chemistry, Triazines, Organic Chemistry, In vitro, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Chemistry (miscellaneous), Molecular Medicine, Drug Screening Assays, Antitumor, 2,4-diamino-1,3,5-triazines, 2-imino-coumarins, Human cancer

الوصف: A series of 2-imino-2H-chromen-3-yl-1,3,5-triazine compounds 5&ndash
12, which are namely hybrids of 2,4-diamino-1,3,5-triazines and 2-imino-coumarins, was synthesized by reacting 2-(4,6-diamine-1,3,5-triazin-2-yl)acetonitriles 1&ndash
4 with 2-hydroxybenzaldehydes. After this, upon heating in aqueous DMF, 2-imino-2H-chromen-3-yl-1,3,5-triazines 10 and 12 were converted into the corresponding 2H-chromen-3-yl-1,3,5-triazines 13 and 14, which are essentially hybrids of 2,4-diamino-1,3,5-triazines and coumarins. The in vitro anticancer activity of the newly prepared compounds was evaluated against five human cancer cell lines: DAN-G, A-427, LCLC-103H, SISO and RT-4. The greatest cytotoxic activity displayed 4-[7-(diethylamino)-2-imino-2H-chromen-3-yl]-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-amine (11, IC50 in the range of 1.51&ndash
2.60 &mu
M).

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08a11ebb75ee043406f268c45df00d31Test

المؤلفون: Martyna Korcz, Franciszek Sączewski, Patrick J. Bednarski, Anita Kornicka

المصدر: Molecules
Volume 23
Issue 6
Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
Molecules, Vol 23, Iss 6, p 1497 (2018)

مصطلحات موضوعية: quinolines, synthesis, Cell Survival, Pharmaceutical Science, Antineoplastic Agents, 1,2,4-triazoles, Ring (chemistry), 01 natural sciences, Medicinal chemistry, Article, Analytical Chemistry, lcsh:QD241-441, chemistry.chemical_compound, Structure-Activity Relationship, lcsh:Organic chemistry, Cell Line, Tumor, Drug Discovery, N-sulfonylhydrazones, in vitro antitumor activity, Moiety, Humans, structure, Physical and Theoretical Chemistry, Methylene, N-acylhydrazones, Benzotriazole, 010405 organic chemistry, Organic Chemistry, Quinoline, 1,2,4-Triazole, Triazoles, In vitro, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, chemistry, Chemistry (miscellaneous), Drug Design, Molecular Medicine, Chemical stability, hydrazones, 1,2,3-benzotriazoles

الوصف: A small library of novel quinoline-3-carbaldehyde hydrazones (Series 1), acylhydrazones (Series 2), and arylsulfonylhydrazones (Series 3) bearing either a 1,2,4-triazole or benzotriazole ring at position 2 was prepared, characterized by elemental analyses and IR, NMR, and MS spectra, and then subjected to in vitro cytotoxicity studies on three human tumor cell lines: DAN-G, LCLC-103H, and SISO. In general, compounds 4, 6, and 8 substituted with a 1,2,4-triazole ring proved to be inactive, whereas the benzotriazole-containing quinolines 5, 7, and 9 elicited pronounced cancer cell growth inhibitory effects with IC50 values in the range of 1.23&ndash
7.39 µ
M. The most potent 2-(1H-benzotriazol-1-yl)-3-[2-(pyridin-2-yl)hydrazonomethyl]quinoline (5e) showed a cytostatic effect on the cancer cell lines, whereas N&prime
[(2-(1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-benzohydrazide (7a) and N&prime
[(2-1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-naphthalene-2-sulfonohydrazide (9h) exhibited selective activity against the pancreas cancer DAN-G and cervical cancer SISO cell lines. Based on the determined IC50 values, the compound 5e seems to be leading compound for further development as anticancer agent.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::093c8a146fc70d3fa15ac84e61a5dd67Test

المؤلفون: Łukasz Balewski, Franciszek Sączewski, Maria Gdaniec, Patrick J. Bednarski, Anna Makowska, Ewa Borys

المصدر: Molecules, Vol 19, Iss 10, Pp 17026-17051 (2014)
Molecules
Volume 19
Issue 10
Pages 17026-17051

مصطلحات موضوعية: Models, Molecular, Stereochemistry, Pharmaceutical Science, chemistry.chemical_element, Antineoplastic Agents, 1-(2-pyridyl)imidazolidin-2-ones, Crystallography, X-Ray, Article, Analytical Chemistry, X-ray crystal structure analysis, lcsh:QD241-441, chemistry.chemical_compound, X-Ray Diffraction, lcsh:Organic chemistry, Coordination Complexes, Neoplasms, copper(II) complexes, Drug Discovery, Pyridine, Organometallic Compounds, Tumor Cells, Cultured, in vitro antitumor activity, Humans, Viability assay, Crystal violet, Physical and Theoretical Chemistry, Alkyl, Group 2 organometallic chemistry, chemistry.chemical_classification, Organic Chemistry, Thiones, Copper, In vitro, chemistry, Chemistry (miscellaneous), X-ray crystallography, 1-(2-pyridyl)imidazolidine-2-thiones, Molecular Medicine

الوصف: Six series of structurally different mono- and binuclear copper(II) complexes 5–10 were obtained by reacting N-(2-pyridyl)imidazolidin-2-ones (1a–l), N,N'-bis(2-pyridyl)imidazolidin-2-ones (2a,b), N-acyl-N'(2-pyridyl)imidazolodin-2-ones (3a–j) and N-(2-pyridyl)imidazolidine-2-thiones (4a–g) with copper(II) chloride at an ambient temperature. The coordination modes of the complexes obtained were established by elemental analysis, IR spectroscopic data and single crystal X-ray diffraction studies. The in vitro cytotoxic activities of both the free ligands and copper(II) complexes were evaluated using a crystal violet microtiter plate assay on five human tumor cell lines: LCLC-103H, A-427, SISO, RT-4 and DAN-G. The free ligands 1–4 at concentration attainable in cancer cells of 20 μM showed no meaningful cytotoxic effect with cell viability in the range of 88%–100%. The most potent copper(II) complex of 1-(6-ethoxy-2-pyridyl)imidazolidin-2-one (6b) exhibited selective cytotoxicity against A-427 lung cancer cell line, while the complexes of 1-(5-methyl-2-pyridyl)imidazolidine-2-thione (5h) and 1-(4-tert-butyl-2-pyridyl)imidazolidine-2-thione (5j) showed cytostatic effect against a whole panel of five human tumor cell lines. In conclusion, the only complexes that showed remarkably increased activity in comparison to the free ligands were those obtained from N-(2-pyridyl)imidazolidine-2-thiones 4c and 4e substituted with alkyl group at position 4 or 5 of pyridine ring.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::444461dc96c1061544f8a1c82fa2fe59Test
http://www.mdpi.com/1420-3049/19/10/17026Test

المؤلفون: Zsolt Sziklavari, Patrick J. Bednarski, Reiner Neu, Michael Ried, Hans-Stefan Hofmann, Claudius Diez, Karla Lehle

المصدر: European Journal of Cardio-Thoracic Surgery. 47:563-566

مصطلحات موضوعية: Mesothelioma, Pulmonary and Respiratory Medicine, Hyperthermia, Lung Neoplasms, Pleural Neoplasms, medicine.medical_treatment, Antineoplastic Agents, Models, Biological, Human lung, Parenchyma, Humans, Medicine, Pneumonectomy, Lung, Cisplatin, Chemotherapy, business.industry, Hyperthermia, Induced, General Medicine, Penetration (firestop), medicine.disease, medicine.anatomical_structure, Chemotherapy, Cancer, Regional Perfusion, Surgery, Cardiology and Cardiovascular Medicine, business, Nuclear medicine, Perfusion, Ex vivo, medicine.drug

الوصف: OBJECTIVES The effects of cisplatin on the lung parenchyma during hyperthermic intrathoracic chemotherapy perfusion have not been analysed in detail. The objective of this study was to evaluate both the concentration and depth of the penetration of cisplatin in human lung tissue after hyperthermic exposure under ex vivo conditions. METHODS This experimental study was approved by the local ethics committee. Twelve patients underwent pulmonary wedge resections after elective thoracic lobectomies were performed (resected lobe), and the lung tissue (approximately 1-2 cm(3)) was incubated (in vitro) with cisplatin (0.05 mg/ml; 60 min, 42°C). Subsequent tissue beds (depth, 0.5 mm; median weight, 70-92 mg) were prepared from the outside to the middle, and the amount of cisplatin per tissue weight was analysed using atomic absorption spectrometry. Afterwards, the penetration of cisplatin depth was calculated and related to the different concentrations per tissue. RESULTS Cisplatin penetrated into the human lung tissue after ex vivo hyperthermic exposure. The median amount of platinum [nmol cisplatin/g lung tissue] decreased significantly (P ≤ 0.05) depending on the penetration depth: 32 nmol/g (1 mm), 20 nmol/g (2 mm) and 6.8 nmol/g (4 mm). The calculated median concentrations of cisplatin (µg/ml) were 2.4 µg/ml (1 mm), 1.4 µg/ml (2 mm) and 0.5 µg/ml (4 mm), respectively. CONCLUSIONS Under ex vivo hyperthermic conditions, cisplatin diffused into human lung tissue. The median penetration depth of the cisplatin was approximately 3-4 mm. The penetration of cisplatin into lung tissue may affect the local therapy of residual tumour cells on the lung surface using hyperthermic intrathoracic chemotherapy perfusion in patients with malignant pleural tumours.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c4f8a28bdaff00c401ab033b2a1d5be6Test
https://doi.org/10.1093/ejcts/ezu217Test

المؤلفون: Kim S. Robinson, Luca Salassa, Virginia Appleyard, Karen Murray, Katharina Korpis, Aron F. Westendorf, Nicola J. Farrer, Renate Grünert, Peter J. Sadler, Julie A. Woods, Alastair M. Thompson, Patrick J. Bednarski

المصدر: Molecular Cancer Therapeutics

مصطلحات موضوعية: Cancer Research, Programmed cell death, Organoplatinum Compounds, Cell Survival, Ultraviolet Rays, Mice, Nude, Antineoplastic Agents, Apoptosis, HL-60 Cells, 010402 general chemistry, 01 natural sciences, Article, Inhibitory Concentration 50, Mice, chemistry.chemical_compound, Annexin, Autophagy, medicine, Animals, Humans, Cytotoxic T cell, Propidium iodide, Clonogenic assay, Cell Shape, Cisplatin, 010405 organic chemistry, Cell Cycle, Photochemical Processes, Xenograft Model Antitumor Assays, 0104 chemical sciences, Oncology, chemistry, Drug Resistance, Neoplasm, Cell culture, Immunology, Biophysics, Female, medicine.drug

الوصف: Photoactivatable PtIV diazido complexes have unusual photobiologic properties. We show here that trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)] complex 3 is a potent photoactivated cytotoxin toward human cancer cells in culture, with an average IC50 value in 13 cell lines of 55 ± 28 μmol/L after 30 minutes (0.12 mW/cm2) photoactivation with UVA, although visible light was also effective. Photoactivated complex 3 was noncross-resistant to cisplatin in 3 of 4 resistant cell lines. Cell swelling but very little blebbing was seen for HL60 cells treated with irradiated complex 3. Unlike cisplatin and etoposide, both of which cause apoptosis in HL60 cells, no apoptosis was observed for UVA-activated complex 3 by the Annexin V/propidium iodide flow cytotometry assay. Changes in the levels of the autophagic proteins LC3B-II and p62 in HL60 cells treated with UVA-activated complex 3 indicate autophagy is active during cell death. In a clonogenic assay with the SISO human cervix cancer cell line, 3 inhibited colony formation when activated by UVA irradiation. Antitumor activity of complex 3 in mice bearing xenografted OE19 esophageal carcinoma tumors was photoaugmented by visible light. Insights into the novel reaction pathways of complex 3 have been obtained from 14N{1H} nuclear magnetic resonance studies, which show that photoactivation pathways can involve release of free azide in buffered solution. Density functional theory (DFT) and time-dependent DFT calculations revealed the dissociative character of singlet and triplet excited states of complex 3, which gives rise to reactive, possibly cytotoxic azidyl radicals. Mol Cancer Ther; 11(9); 1894–904. ©2012 AACR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96b41f080da70ff3f659c50f6473774bTest
https://doi.org/10.1158/1535-7163.mct-11-0959Test

المؤلفون: Gerhard Hamilton, Matthias Tacke, Ulrike Olszewski, Patrick J. Bednarski, Megan Hogan, Robert Zeillinger, James Claffey

المصدر: Investigational New Drugs. 29:607-614

مصطلحات موضوعية: Cell cycle checkpoint, DNA damage, Down-Regulation, Antineoplastic Agents, Stathmin, Cell Line, Tumor, Organometallic Compounds, medicine, Humans, Pharmacology (medical), Cell Proliferation, Platinum, Pharmacology, Cisplatin, biology, Genome, Human, Cell growth, Gene Expression Profiling, Topoisomerase, Cell Cycle, Cell cycle, Molecular biology, Up-Regulation, Gene Expression Regulation, Neoplastic, Oncology, Drug Resistance, Neoplasm, Cell culture, biology.protein, Drug Screening Assays, Antitumor, medicine.drug

الوصف: Titanocenes constitute a class of metal-based anticancer agents that seem to display a mode of action distinct from that of platinum complexes and to be more tolerable with a differing spectrum of activity. In the present study, titanocene C (bis-(N,N-dimethylamino-2(N-methylpyrrolyl)-methyl-cyclopentadienyl) titanium(IV) dichloride) was shown to exhibit antiproliferative activity against human tumor cell lines with a mean IC₅₀ value of 48.3 ± 32.5 µM. In particular, high activity was found against small cell lung cancer (SCLC) cell lines with a profile different from cisplatin. Titanocene C induced cell cycle arrest at the G1/0-S interphase. Cross-resistance to either cisplatin or oxoplatin, respectively, was low for titanocene C and absent for titanocene Y in variant HL-60 cell lines. Alterations in gene expression of NCI-H526 SCLC cells induced by titanocene C were investigated using genome-wide expression arrays. Downregulation was found for genes coding for topoisomerases I and IIα, histones of the HIST1H4 cluster, enzymes involved in glycolysis, components of the cytoskeleton and vesicular transport, among others. In contrast, expression of genes involved in apoptosis, stress response, particularly members of the metallothionein gene cluster 1, DNA damage and growth factors was upregulated following exposure to titanocene C. Approximately 50% of those genes downregulated by titanocene C and cisplatin were concordant, including the previously identified markers of cisplatin-sensitivity, tubulin and stathmin, indicating partial overlap of the pathways affected by these metal complexes. The present findings point helicases/topoisomerases and HIST1H4 core histones out as targets of titanocene C and metallothioneins as putative main effectors of drug resistance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ca82d51beb483308bd1717ae58dd0392Test
https://doi.org/10.1007/s10637-010-9395-5Test