Danijela Maksimović-ivanić - Academia.edu (original) (raw)

Papers by Danijela Maksimović-ivanić

Research paper thumbnail of Effect of chain length on the cytotoxic activity of (alkyl-ω-ol)triphenyltin(IV) loaded into SBA-15 nanostructured silica and in vivo study of SBA-15~Cl|Ph3Sn(CH2)8OH

Research paper thumbnail of Arene Ruthenium(II) Complexes Bearing the κ-P or κ-P,κ-S Ph2P(CH2)3SPh Ligand

Molecules

Neutral [Ru(η6-arene)Cl2{Ph2P(CH2)3SPh-κP}] (arene = benzene, indane, 1,2,3,4-tetrahydronaphthale... more Neutral [Ru(η6-arene)Cl2{Ph2P(CH2)3SPh-κP}] (arene = benzene, indane, 1,2,3,4-tetrahydronaphthalene: 2a, 2c and 2d) and cationic [Ru(η6-arene)Cl(Ph2P(CH2)3SPh-κP,κS)]X complexes (arene = mesitylene, 1,4-dihydronaphthalene; X = Cl: 3b, 3e; arene = benzene, mesitylene, indane, 1,2,3,4-tetrahydronaphthalene, and 1,4-dihydronaphthalene; X = PF6: 4a–4e) complexes were prepared and characterized by elemental analysis, IR, 1H, 13C and 31P NMR spectroscopy and also by single-crystal X-ray diffraction analyses. The stability of the complexes has been investigated in DMSO. Complexes have been assessed for their cytotoxic activity against 518A2, 8505C, A253, MCF-7 and SW480 cell lines. Generally, complexes exhibited activity in the lower micromolar range; moreover, they are found to be more active than cisplatin. For the most active ruthenium(II) complex, 4b, bearing mesitylene as ligand, the mechanism of action against 8505C cisplatin resistant cell line was determined. Complex 4b induced apo...

Research paper thumbnail of Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro

Molecules, Nov 22, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors

Research paper thumbnail of Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines

Nanomaterials

The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin incl... more The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin include drug resistance and significant side effects. Due to their better stability, as well as the possibility to introduce biologically active ligands in their axial positions constructing multifunctional prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations. Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV) conjugates demonstrated higher or comparable activity with respect to cisplatin against different human breast cance...

Research paper thumbnail of Borcalein: a Carborane‐Based Analogue of Baicalein with 12‐Lipoxygenase‐Independent Toxicity

ChemMedChem, 2021

12‐Lipoxygenase is crucial for tumour angiogenesis. 5,6,7‐Trihydroxy‐2‐phenyl‐4H‐1‐benzopyran‐4‐o... more 12‐Lipoxygenase is crucial for tumour angiogenesis. 5,6,7‐Trihydroxy‐2‐phenyl‐4H‐1‐benzopyran‐4‐one (baicalein) is a suitable inhibitor for this enzyme but is rapidly metabolised in vivo. Thus, an improvement of the metabolic stability is necessary to enhance the therapeutic efficiency. An emerging approach to enhance metabolic stability of carbon‐based pharmaceuticals is the use of metabolically stable, non‐toxic boron clusters, such as dicarba‐closo‐dodecaborane(12)s (carboranes) as phenyl mimetics. Therefore, the unsubstituted phenyl ring of baicalein was replaced by meta‐carborane, resulting in borcalein, the carborane analogue of baicalein. This substitution resulted in a decreased inhibitory activity toward 12‐lipoxygenase, but led to increased toxicity in melanoma (A375, B16, B16F10) and colon cancer cell lines (SW480, HCT116, CT26CL25) with decreased tumour selectivity in comparison to baicalein. Surprisingly, borcalein displays a different mechanism of cytotoxicity with increased intracellular production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO).

Research paper thumbnail of HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?

International journal of cancer, Apr 21, 2016

The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment ... more The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV-related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma, and prostate cancer suggest other mechanisms for the anti-neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV-PIs in the therapy of cancer relies on their relatively weak anticancer potency, and important side effects. This has propelled several groups to generate derivatives of HIV-PIs for anticancer use, through modifications such as attachment of different moieties, ligands, and transporters, including saquinavir-loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV-PIs. In this paper, we discuss the current preclinica...

Research paper thumbnail of In vitro assessment of Ni-Cr and Co-Cr dental alloys upon recasting: Cellular compatibility

Digest Journal of Nanomaterials and Biostructures

The aim of this study was to evaluate the effect of recasting of commercially available Ni-Cr (Wi... more The aim of this study was to evaluate the effect of recasting of commercially available Ni-Cr (Wiron 99) and Co-Cr (Dentalit C) dental alloys on physiology of microenvironmental cells. The viability of fibrosarcoma (L929) cells, human embrional fibroblasts (MRC-5) and isolated peripheral blood mononuclear cells (PBMC) was measured by MTT and acidic phosphatase tests. Presence of dying cells was estimated by Annexin/PI staining while the production of intracellular nitric oxide (NO), reactive oxygen (ROS) and nitrogen (RNS) species was determined by DAF-FM diacetate and DHR staining. Recasting of Ni-Cr alloy intensified its cytotoxicity manifested through enhanced free radicals production, induction of cell death and permamently diminished cell proliferation. On the other hand, after initial toxic effect cells adapted to the presence of Co-Cr alloys. Independently of recasting, Co-Cr alloys are more compatible with microenvironment then Ni-Cr alloy. Oppositely, recasting of Ni-Cr alloy promoted its toxicity.

Research paper thumbnail of Inhibition of autoimmune diabetes by mycophenolate mofetil is associated with down-regulation of TH1 cytokine-induced apoptosis in the target tissue

Transplantation Proceedings, 2002

Research paper thumbnail of Study of the anticancer properties of methyl- and phenyl-substituted carbon- and silicon-bridged ansa-titanocene complexes

Journal of Organometallic Chemistry, 2014

The previously known complexes [Ti{(Me 2 CMe 2 C)(h 5-C 5 H 4) 2 }Cl 2 ] (1), [Ti{Me 2 C(h 5-C 5 ... more The previously known complexes [Ti{(Me 2 CMe 2 C)(h 5-C 5 H 4) 2 }Cl 2 ] (1), [Ti{Me 2 C(h 5-C 5 H 4) 2 }Cl 2 ] (2), [Ti {Me 2 Si(h 5-C 5 H 4) 2 }Cl 2 ] (4), [Ti{MePhSi(h 5-C 5 H 4) 2 }Cl 2 ] (5) and [Ti{MePhSi(h 5-C 5 Me 4) 2 }Cl 2 ] (6) have been prepared following reported procedures. The novel complex [Ti{MePhC(h 5-C 5 H 4) 2 }Cl 2 ] (3) has been prepared and characterized. The cytotoxic activity of 1e6 has been tested after 72 h on melanoma A375 and B16, prostate cancer DU145 and LNCaP and colon cancer HCT116, SW620 and CT26CL25 cell lines observing a high cytotoxic activity of complexes 1 and 6 compared to the reference compound ([Ti(h 5-C 5 H 5) 2 }Cl 2 ]). 1 and 6 have also been tested against primary normal mouse keratinocytes and lung fibroblasts. While viability of both type of primary cells was significantly less affected by 1 in comparison to the reference compound [Ti(h 5-C 5 H 5) 2 Cl 2 ], compound 6 was completely nontoxic for nonmalignant cells, indicating a potential selectivity of this compound towards cancer cell lines. In addition CFSE staining, cell cycle analysis, AnnexinV-FITC/PI staining, detection of caspase activity and mitochondrial potential showed that 1 and 6 were acting through inhibition of proliferation and subsequent induction of mitochondrial dependent apoptosis in colon cancer cell lines, HCT116 and SW620, which express low sensitivity to cisplatin. Compound 6 was found to be the leading drug in this group since it shows the fastest and most selective anticancer profile.

Research paper thumbnail of Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO

Free Radical Biology and Medicine, 2010

The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the anti-i... more The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the anti-inflammatory isoxazoline VGX-1027. The compound has been shown to possess powerful anticancer effects both in vitro and in vivo. However, its effects on nonsolid and metastatic forms of tumors have not yet been investigated. We have studied the effects of GIT-27NO on the highly invasive mouse mammary TA3Ha cell line in vitro and in vivo. In contrast to the conventional exogenous NO donor sodium nitroprusside, GIT-27NO successfully enhanced intracellular NO concentration in TA3Ha cells. Intracellular accumulation of NO was followed by marked decrease in TA3Ha cell viability accompanied by typical apoptotic features. Interestingly, inverted membrane phosphatidylserine residues, reduced volume of nucleus, condensed chromatin, and terminal fragmentation of DNA were associated with inhibited caspase-3 activity and transcription of the genes encoding caspase-3, -8, and -9. In parallel, GIT-27NO rapidly but transiently prevented the loss of p53 through phosphorylation on Ser 20 and provided the necessary signals for the execution of downstream processes without p53 de novo synthesis. The caspase-independent apoptotic-like death process triggered by GIT-27NO could be mediated by markedly down-regulated expression of the antiapoptotic Bcl-2 molecule observed in TA3Ha cells exposed to GIT-27NO. In agreement with these in vitro data, GIT-27NO efficiently suppressed the growth of the ascites form and associated lethality of tumor induced by TA3Ha cells in mice.

Research paper thumbnail of Aloe emodin inhibits the cytotoxic action of tumor necrosis factor

European Journal of Pharmacology, 2007

We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of ... more We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation.

Research paper thumbnail of Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin

Cellular and Molecular Life Sciences, 2005

The present study describes the ability of an anthraquinone derivative aloe emodin (AE) to reduce... more The present study describes the ability of an anthraquinone derivative aloe emodin (AE) to reduce the cytotoxic activity of the platinum(II)-based anticancer agent cisplatin toward murine L929 fibrosarcoma and C6 glioma cell lines. The protective effect of AE was demonstrated by MTT and crystal violet assays for cell viability, and involved supression of cisplatin-induced apoptosis and necrosis, as assessed by lactate dehydrogenase release and flow cytometric analysis of DNA fragmentation or phosphatidylserine exposure. Cell-based ELISA and Western blot analysis revealed that AE abolished cisplatin-triggered activation of extracellular signal-regulated kinase (ERK) in tumor cells, while activation of c-Jun N-terminal kinase was not significantly altered. A selective blockade of ERK activation with PD98059 mimicked the protective effect of AE treatment in both tumor cell lines. Moreover, AE failed to protect tumor cells against the ERK-independent toxicity of the Pt(IV)-based complex tetrachloro(O,O-dibutyl-ethylenediamine-N,N'-di-3-propanoate)platinum(IV). Taken together, these data indicate that herbal anthraquinone AE can downregulate the anticancer activity of cisplatin by blocking the activation of ERK in tumor cells.

Research paper thumbnail of Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo

Molecules

Lipoxygenases convert polyunsaturated fatty acids into biologically active metabolites such as in... more Lipoxygenases convert polyunsaturated fatty acids into biologically active metabolites such as inflammatory mediators—prostaglandins and leukotrienes. The inhibition of lipoxygenases is increasingly employed in the treatment of cancer. We evaluated the anticancer potential of two novel 5-lipoxygenase inhibitors, named CarbZDNaph and CarbZDChin, which are analogues of the commercially available inhibitor Rev-5901. The in vitro segment of this study was conducted on a mouse colorectal carcinoma cell line—CT26CL25. For an in vivo model, we induced tumors in BALB/c mice by the implantation of CT26CL25 cells, and we treated the animals with potential inhibitors. A 48 h treatment resulted in diminished cell viability. Calculated IC50 values (half-maximal inhibitory concentrations) were 25 μM, 15 μM and 30 μM for CarbZDNaph, CarbZDChin and Rev-5901, respectively. The detailed analysis of mechanism revealed an induction of caspase-dependent apoptosis and autophagy. In the presence of chloro...

Research paper thumbnail of Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation

Research paper thumbnail of Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro

Nanomaterials

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of CCDC 1413063: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of CCDC 1523470: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of CCDC 1523469: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of CCDC 945341: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of Effect of chain length on the cytotoxic activity of (alkyl-ω-ol)triphenyltin(IV) loaded into SBA-15 nanostructured silica and in vivo study of SBA-15~Cl|Ph3Sn(CH2)8OH

Research paper thumbnail of Arene Ruthenium(II) Complexes Bearing the κ-P or κ-P,κ-S Ph2P(CH2)3SPh Ligand

Molecules

Neutral [Ru(η6-arene)Cl2{Ph2P(CH2)3SPh-κP}] (arene = benzene, indane, 1,2,3,4-tetrahydronaphthale... more Neutral [Ru(η6-arene)Cl2{Ph2P(CH2)3SPh-κP}] (arene = benzene, indane, 1,2,3,4-tetrahydronaphthalene: 2a, 2c and 2d) and cationic [Ru(η6-arene)Cl(Ph2P(CH2)3SPh-κP,κS)]X complexes (arene = mesitylene, 1,4-dihydronaphthalene; X = Cl: 3b, 3e; arene = benzene, mesitylene, indane, 1,2,3,4-tetrahydronaphthalene, and 1,4-dihydronaphthalene; X = PF6: 4a–4e) complexes were prepared and characterized by elemental analysis, IR, 1H, 13C and 31P NMR spectroscopy and also by single-crystal X-ray diffraction analyses. The stability of the complexes has been investigated in DMSO. Complexes have been assessed for their cytotoxic activity against 518A2, 8505C, A253, MCF-7 and SW480 cell lines. Generally, complexes exhibited activity in the lower micromolar range; moreover, they are found to be more active than cisplatin. For the most active ruthenium(II) complex, 4b, bearing mesitylene as ligand, the mechanism of action against 8505C cisplatin resistant cell line was determined. Complex 4b induced apo...

Research paper thumbnail of Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro

Molecules, Nov 22, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors

Research paper thumbnail of Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines

Nanomaterials

The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin incl... more The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin include drug resistance and significant side effects. Due to their better stability, as well as the possibility to introduce biologically active ligands in their axial positions constructing multifunctional prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations. Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV) conjugates demonstrated higher or comparable activity with respect to cisplatin against different human breast cance...

Research paper thumbnail of Borcalein: a Carborane‐Based Analogue of Baicalein with 12‐Lipoxygenase‐Independent Toxicity

ChemMedChem, 2021

12‐Lipoxygenase is crucial for tumour angiogenesis. 5,6,7‐Trihydroxy‐2‐phenyl‐4H‐1‐benzopyran‐4‐o... more 12‐Lipoxygenase is crucial for tumour angiogenesis. 5,6,7‐Trihydroxy‐2‐phenyl‐4H‐1‐benzopyran‐4‐one (baicalein) is a suitable inhibitor for this enzyme but is rapidly metabolised in vivo. Thus, an improvement of the metabolic stability is necessary to enhance the therapeutic efficiency. An emerging approach to enhance metabolic stability of carbon‐based pharmaceuticals is the use of metabolically stable, non‐toxic boron clusters, such as dicarba‐closo‐dodecaborane(12)s (carboranes) as phenyl mimetics. Therefore, the unsubstituted phenyl ring of baicalein was replaced by meta‐carborane, resulting in borcalein, the carborane analogue of baicalein. This substitution resulted in a decreased inhibitory activity toward 12‐lipoxygenase, but led to increased toxicity in melanoma (A375, B16, B16F10) and colon cancer cell lines (SW480, HCT116, CT26CL25) with decreased tumour selectivity in comparison to baicalein. Surprisingly, borcalein displays a different mechanism of cytotoxicity with increased intracellular production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO).

Research paper thumbnail of HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?

International journal of cancer, Apr 21, 2016

The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment ... more The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV-related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma, and prostate cancer suggest other mechanisms for the anti-neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV-PIs in the therapy of cancer relies on their relatively weak anticancer potency, and important side effects. This has propelled several groups to generate derivatives of HIV-PIs for anticancer use, through modifications such as attachment of different moieties, ligands, and transporters, including saquinavir-loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV-PIs. In this paper, we discuss the current preclinica...

Research paper thumbnail of In vitro assessment of Ni-Cr and Co-Cr dental alloys upon recasting: Cellular compatibility

Digest Journal of Nanomaterials and Biostructures

The aim of this study was to evaluate the effect of recasting of commercially available Ni-Cr (Wi... more The aim of this study was to evaluate the effect of recasting of commercially available Ni-Cr (Wiron 99) and Co-Cr (Dentalit C) dental alloys on physiology of microenvironmental cells. The viability of fibrosarcoma (L929) cells, human embrional fibroblasts (MRC-5) and isolated peripheral blood mononuclear cells (PBMC) was measured by MTT and acidic phosphatase tests. Presence of dying cells was estimated by Annexin/PI staining while the production of intracellular nitric oxide (NO), reactive oxygen (ROS) and nitrogen (RNS) species was determined by DAF-FM diacetate and DHR staining. Recasting of Ni-Cr alloy intensified its cytotoxicity manifested through enhanced free radicals production, induction of cell death and permamently diminished cell proliferation. On the other hand, after initial toxic effect cells adapted to the presence of Co-Cr alloys. Independently of recasting, Co-Cr alloys are more compatible with microenvironment then Ni-Cr alloy. Oppositely, recasting of Ni-Cr alloy promoted its toxicity.

Research paper thumbnail of Inhibition of autoimmune diabetes by mycophenolate mofetil is associated with down-regulation of TH1 cytokine-induced apoptosis in the target tissue

Transplantation Proceedings, 2002

Research paper thumbnail of Study of the anticancer properties of methyl- and phenyl-substituted carbon- and silicon-bridged ansa-titanocene complexes

Journal of Organometallic Chemistry, 2014

The previously known complexes [Ti{(Me 2 CMe 2 C)(h 5-C 5 H 4) 2 }Cl 2 ] (1), [Ti{Me 2 C(h 5-C 5 ... more The previously known complexes [Ti{(Me 2 CMe 2 C)(h 5-C 5 H 4) 2 }Cl 2 ] (1), [Ti{Me 2 C(h 5-C 5 H 4) 2 }Cl 2 ] (2), [Ti {Me 2 Si(h 5-C 5 H 4) 2 }Cl 2 ] (4), [Ti{MePhSi(h 5-C 5 H 4) 2 }Cl 2 ] (5) and [Ti{MePhSi(h 5-C 5 Me 4) 2 }Cl 2 ] (6) have been prepared following reported procedures. The novel complex [Ti{MePhC(h 5-C 5 H 4) 2 }Cl 2 ] (3) has been prepared and characterized. The cytotoxic activity of 1e6 has been tested after 72 h on melanoma A375 and B16, prostate cancer DU145 and LNCaP and colon cancer HCT116, SW620 and CT26CL25 cell lines observing a high cytotoxic activity of complexes 1 and 6 compared to the reference compound ([Ti(h 5-C 5 H 5) 2 }Cl 2 ]). 1 and 6 have also been tested against primary normal mouse keratinocytes and lung fibroblasts. While viability of both type of primary cells was significantly less affected by 1 in comparison to the reference compound [Ti(h 5-C 5 H 5) 2 Cl 2 ], compound 6 was completely nontoxic for nonmalignant cells, indicating a potential selectivity of this compound towards cancer cell lines. In addition CFSE staining, cell cycle analysis, AnnexinV-FITC/PI staining, detection of caspase activity and mitochondrial potential showed that 1 and 6 were acting through inhibition of proliferation and subsequent induction of mitochondrial dependent apoptosis in colon cancer cell lines, HCT116 and SW620, which express low sensitivity to cisplatin. Compound 6 was found to be the leading drug in this group since it shows the fastest and most selective anticancer profile.

Research paper thumbnail of Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO

Free Radical Biology and Medicine, 2010

The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the anti-i... more The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the anti-inflammatory isoxazoline VGX-1027. The compound has been shown to possess powerful anticancer effects both in vitro and in vivo. However, its effects on nonsolid and metastatic forms of tumors have not yet been investigated. We have studied the effects of GIT-27NO on the highly invasive mouse mammary TA3Ha cell line in vitro and in vivo. In contrast to the conventional exogenous NO donor sodium nitroprusside, GIT-27NO successfully enhanced intracellular NO concentration in TA3Ha cells. Intracellular accumulation of NO was followed by marked decrease in TA3Ha cell viability accompanied by typical apoptotic features. Interestingly, inverted membrane phosphatidylserine residues, reduced volume of nucleus, condensed chromatin, and terminal fragmentation of DNA were associated with inhibited caspase-3 activity and transcription of the genes encoding caspase-3, -8, and -9. In parallel, GIT-27NO rapidly but transiently prevented the loss of p53 through phosphorylation on Ser 20 and provided the necessary signals for the execution of downstream processes without p53 de novo synthesis. The caspase-independent apoptotic-like death process triggered by GIT-27NO could be mediated by markedly down-regulated expression of the antiapoptotic Bcl-2 molecule observed in TA3Ha cells exposed to GIT-27NO. In agreement with these in vitro data, GIT-27NO efficiently suppressed the growth of the ascites form and associated lethality of tumor induced by TA3Ha cells in mice.

Research paper thumbnail of Aloe emodin inhibits the cytotoxic action of tumor necrosis factor

European Journal of Pharmacology, 2007

We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of ... more We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation.

Research paper thumbnail of Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin

Cellular and Molecular Life Sciences, 2005

The present study describes the ability of an anthraquinone derivative aloe emodin (AE) to reduce... more The present study describes the ability of an anthraquinone derivative aloe emodin (AE) to reduce the cytotoxic activity of the platinum(II)-based anticancer agent cisplatin toward murine L929 fibrosarcoma and C6 glioma cell lines. The protective effect of AE was demonstrated by MTT and crystal violet assays for cell viability, and involved supression of cisplatin-induced apoptosis and necrosis, as assessed by lactate dehydrogenase release and flow cytometric analysis of DNA fragmentation or phosphatidylserine exposure. Cell-based ELISA and Western blot analysis revealed that AE abolished cisplatin-triggered activation of extracellular signal-regulated kinase (ERK) in tumor cells, while activation of c-Jun N-terminal kinase was not significantly altered. A selective blockade of ERK activation with PD98059 mimicked the protective effect of AE treatment in both tumor cell lines. Moreover, AE failed to protect tumor cells against the ERK-independent toxicity of the Pt(IV)-based complex tetrachloro(O,O-dibutyl-ethylenediamine-N,N'-di-3-propanoate)platinum(IV). Taken together, these data indicate that herbal anthraquinone AE can downregulate the anticancer activity of cisplatin by blocking the activation of ERK in tumor cells.

Research paper thumbnail of Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo

Molecules

Lipoxygenases convert polyunsaturated fatty acids into biologically active metabolites such as in... more Lipoxygenases convert polyunsaturated fatty acids into biologically active metabolites such as inflammatory mediators—prostaglandins and leukotrienes. The inhibition of lipoxygenases is increasingly employed in the treatment of cancer. We evaluated the anticancer potential of two novel 5-lipoxygenase inhibitors, named CarbZDNaph and CarbZDChin, which are analogues of the commercially available inhibitor Rev-5901. The in vitro segment of this study was conducted on a mouse colorectal carcinoma cell line—CT26CL25. For an in vivo model, we induced tumors in BALB/c mice by the implantation of CT26CL25 cells, and we treated the animals with potential inhibitors. A 48 h treatment resulted in diminished cell viability. Calculated IC50 values (half-maximal inhibitory concentrations) were 25 μM, 15 μM and 30 μM for CarbZDNaph, CarbZDChin and Rev-5901, respectively. The detailed analysis of mechanism revealed an induction of caspase-dependent apoptosis and autophagy. In the presence of chloro...

Research paper thumbnail of Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation

Research paper thumbnail of Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro

Nanomaterials

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of CCDC 1413063: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of CCDC 1523470: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of CCDC 1523469: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Research paper thumbnail of CCDC 945341: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.