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Tumor cells circumvent the anti-tumor host immune response by generating an immunosuppressive network. Tumor cells evade the surveillance mechanisms of host immune system in a process called immune editing resulting in the generation of an immunosuppressive network that leads to malignant progression. In the process of immune editing tumor derived soluble factors (such as TGF-b, IL-10, IL 4, IL 6, IL 13, VEGF, GM-CSF, CSF 1, IL-1b, PGE 2 , IDO) block the effector immune cell functions either directly or indirectly by promoting migration and expansion of regulatory cell population such as tumor associated macrophages (TAMs), Myeloid derived suppressor cells (MDSCs), T-regulatory cells (T Reg ) in the tumor site. Specifically, secretion of IL-10, IL 4, IL 6, IL 13, CSF 1 recruit the monocytes in the growing tumor site and educate the newly recruited monocytes to differentiate into TAMs which negatively regulate the effector T-cell response through releasing wide range immunosuppressive factors like TGF-b, IL-10, PGE 2. TAMs with its suppressive cytokine profile also induce the generation of T-regulatory cells (T Reg ). These regulatory cell populations possess a characteristic anergic phenotype and block T-effector cells through both direct interaction and the production of immunosuppressive cytokines such as TGF-b and IL-10. Besides TAMs, tumor cells themselves can promote the induction of T Reg in the tumor site through secreting CCL 22, PGE 2. In addition to this, liberation of GM-CSF, IL-1b, VEGF and PGE 2 by tumor cells leads to the infiltration of another suppressive population MDSCs in the tumor microenvironment and MDSCs in turn abrogate T cell function by expressing TGF-b, ARG1, and iNOS.
Source publication
Drug resistance is a problem that hinders the numerous successes of chemotherapeutic intervention of cancer and continues to be a major obstacle for cures. Till date, several attempts have been made to develop suitable multi drug resistance (MDR) reversing agents. But, throughout the clinical development of MDR reversing agents, patients repeatedly...
Contexts in source publication
Context 1
... immunosuppressive factors such as IL-4, IL-13, GM-CSF, IL-1b, VEGF, or PGE2 and alterations in the nutrient content of the microenvironment. Specifically, secretion of IL-4 and IL-13 leads to polarization of M2 macrophages or tumor associated macrophage (TAM) from myeloid precursors, which express high TGF-b, IL-10, and PDGF that inhibit T cells (Fig. 5). The release of colony-stimulating factors, IL-1b, VEGF, or PGE2 by tumor cells results in the accumulation of MDSCs that can block T cell function by expressing TGF-b, ARG1, and iNOS (Fig. 5) (Vesely et al., 2011). In addition to this, through a number of tumor-derived factors (including IL-6, IL-10, GM-CSF, M-CSF, or VEGF), tumours ...
Context 2
... polarization of M2 macrophages or tumor associated macrophage (TAM) from myeloid precursors, which express high TGF-b, IL-10, and PDGF that inhibit T cells (Fig. 5). The release of colony-stimulating factors, IL-1b, VEGF, or PGE2 by tumor cells results in the accumulation of MDSCs that can block T cell function by expressing TGF-b, ARG1, and iNOS (Fig. 5) (Vesely et al., 2011). In addition to this, through a number of tumor-derived factors (including IL-6, IL-10, GM-CSF, M-CSF, or VEGF), tumours alter DC differentiation; promote accumulation of iDCs and increase differentiation and expansion of pDCs. These immunosuppressive DCs are ineffective in stimulation of immune responses but can ...
Context 3
... accumulation of iDCs and increase differentiation and expansion of pDCs. These immunosuppressive DCs are ineffective in stimulation of immune responses but can induce T cell tolerance by employing variety of regulatory mechanisms (Rabinovich et al., 2007). Regulatory T cells (Tregs) can also inhibit effector T cells through multiple mechanisms (Fig. 5), including expression of CTLA-4 (Vesely et al., ...
Context 4
... factors such as IL-4, IL-13, GM-CSF, IL-1b, VEGF, or PGE2 and alterations in the nutrient content of the microenvironment. Specifically, secre- tion of IL-4 and IL-13 leads to polarization of M2 macrophages or tumor associated macrophage (TAM) from myeloid precursors, which express high TGF-b, IL-10, and PDGF that inhibit T cells (Fig. 5). The release of colony-stimulating factors, IL-1b, VEGF, or PGE2 by tumor cells results in the accumulation of MDSCs that can block T cell function by expressing TGF-b, ARG1, and iNOS (Fig. 5) (Vesely et al., 2011). In addition to this, through a number of tumor-derived factors (including IL-6, IL-10, GM-CSF, M-CSF, or VEGF), tumours ...
Context 5
... polarization of M2 macrophages or tumor associated macrophage (TAM) from myeloid precursors, which express high TGF-b, IL-10, and PDGF that inhibit T cells (Fig. 5). The release of colony-stimulating factors, IL-1b, VEGF, or PGE2 by tumor cells results in the accumulation of MDSCs that can block T cell function by expressing TGF-b, ARG1, and iNOS (Fig. 5) (Vesely et al., 2011). In addition to this, through a number of tumor-derived factors (including IL-6, IL-10, GM-CSF, M-CSF, or VEGF), tumours alter DC differentiation; promote accumulation of iDCs and increase differentiation and expansion of pDCs. These immunosuppressive DCs are ineffective in stimulation of immune responses but can ...
Context 6
... accumulation of iDCs and increase differentiation and expansion of pDCs. These immunosuppressive DCs are ineffective in stimulation of immune responses but can induce T cell tolerance by employing variety of regulatory mechanisms (Rabinovich et al., 2007). Regulatory T cells (Tregs) can also inhibit effector T cells through multiple mecha- nisms (Fig. 5), including expression of CTLA-4 (Vesely et al., ...
Citations
... Schiff bases (-CH¼N-) are one of the most important biomolecules in medicinal and pharmaceutical fields. [1][2][3][4][5] Some examples of bioactive Schiff bases linked with heterocyclic moiety are Schiff base A bearing benzimidazole, furan and thiadiazole moieties showed a potential antibacterial activity against the three bacterial strains (Staphylococcus aureus, Escherichia coli, and Bacillus pumilus) [6] and Schiff base B bearing 1, 3, 4-thiadiazole with 1, 2, 4-triazol-3-thione showed antituberculosis activity and acetylcholinesterase inhibition effect. [7] Also, Schiff base C which bearing 1, 3, 4-oxadiazole moiety showed inhibitor of a-glucosidase. ...
Inflammation is a fundamental physiological process that is essential for survival of human being but at the same time is one of the major causes of human morbidity and mortality. In the past decade, numerous advances have taken place in the understanding and development of novel anti-inflammatory drugs. Therefore, investigation of newest anti-inflammatory agents is still a major challenge. In this study, novel and successfully synthesized naproxen-derivatives indicated powerful anti-inflammatory properties as potent of COX-1 and/or COX-2 inhibitors are reported. Results obtained revealed the presence of very potent derivatives with% inhibition of the oedema by 100% in addition to enzyme inhibition values that can reach 92%. The molecular docking and molecular dynamic calculations have been studied. Thus, new potent candidates for further investigation as prospective non-steroidal anti-inflammatory drug were proposed. Furthermore, twenty of the synthesized derivatives have been selected by the NCI, USA for anti-cancer screening and some of the tested compounds showed good% growth inhibition and some selectivity against some cell lines such as melanoma, non-small cell lung and colon cancer with GI% val- ues ranging from 60.9 to 82.8%. Structure activity relationship has been performed and molecular mod- eling studies and molecular dynamic simulations have been performed for more explanation of the action of the synthesized compounds.
... Schiff bases have played a key role as chelating and widely used ligands in main group and transition metal coordination chemistry due to their ease of synthesis, stability under a variety of oxidative and reductive conditions, and the structural versatility associated with their diverse applications [20][21][22][23][24][25]. A large number of Schiff bases and their metal complexes have been studied for their interesting and important properties, for example, their catalytic activity [26][27][28][29][30][31][32], photochromic properties [33], and use as potential antitumor drugs [34][35][36]. ...
The coordination chemistry of butane-2,3-dione bis (2′-pyridylhydrazone) towards the divalent first-row transition metals zinc and iron has been explored. Depending upon the conditions, the ligand in the six complexes was found to be either neutral, mono, or doubly deprotonated. The zinc(II) and iron(II) complexes were fully characterized by elemental analysis, mass spectrometry, and X-ray diffraction methods.
... It is therefore important to develop new, safe and more effective drugs for treating cancer. Schiff bases are aldehyde or ketone derivatives in which the carbonyl group is replaced by an imine or azomethine group [8]. They are widely used in industry and have also been found to exhibit a broad range of biological activities such as antifungal [9], antiinflammatory [10], Antileishmanial [11], antimicrobial [12][13][14] , anti-cancer [15][16][17]. ...
The incidence and prevalence of cancer has been on the rise in recent years and this has been linked to environmental factors, adoption of westernized lifestyle and aging populations. This situation is further complicated by the inadequacies of currently used anticancer agents such as toxicity and resistance which has prompted the search for new and more effective drugs. In this study, Schiff bases of 5-aminotetrazole were prepared by condensing 5- aminotetrazole with various aromatic aldehydes. Preliminary confirmation of compound formation was done using thin layer chromatography while FT-IR, UV-Visible, proton and carbon-13 NMR spectroscopy were used for structural characterization of the compounds. The cytotoxicity of the compounds was evaluated using the brine shrimplethality assay. The compounds were synthesized in good yield ranging from 80 to 88 % and found to be soluble in polar solvents. Results of the spectroscopic analyses were indicative of the formation of the new compounds. The 5- aminotetrazole Schiff bases were found to demonstrate considerable cytotoxicity compared to the standard drug used, with the o-vanillin Schiff base (OVASB) showing the highest cytotoxicity (LC50 0.23 µg/mL). The results indicate that the compounds have potential for further development in the search for safe and potent anticancer agents. Keywords: Cancer; Schiff base; 5-Aminotetrazole; Aromatic aldehydes; Brine shrimp assay
... [1][2][3] The integration of the thermo-chemo therapeutic system consisting of gold nanocomposites, 4 carbon nanotubes, 5 and magnetic mesoporous microspheres 6 is an effective therapeutic system in vitro and vivo. Despite achievements that have been made, the integrated therapeutic systems usually loading an exogenous drug (doxorubicin, paclitaxel, and macromolecular protein), which commonly bring undesirable side effects, ineffective delivery to the tumor sites, and tumor cell resistance, [7][8][9] are still facing difficult problems. Nitric oxide (NO) as a messenger molecule in vivo plays an important role in many physiological activities, such as cardiovascular, cerebrovascular, respiratory, nervous, and immune response. ...
Introduction
Aim to obtain a NO donor that can control released NO in vivo with the high efficacy of tumor suppression and targeting, a nanoplatform consisting of FA-Fe3O4@mSiO2-Au/DOX was constructed.
Methods
In vitro, the nanoplatform catalyzed NO’s release with the maximum value of 4.91 μM within 60 min at 43°C pH=5.0, which was increased by 1.14 times when the temperature was 37°C. In vivo, 11.7 μg Au in the tumor tissue was found to catalyze S-nitrosoglutathione continuously, and 54 μM NO was checked out in the urine.
Results and Discussion
The high concentration of NO was found to increase the apoptotic rate and to reduce tumor proliferation. In the chemo-photothermal combination therapy, the tumor inhibition rate was increased up to 94.3%, and Au’s contribution from catalyzing NO release NO was 8.17%.
... Schiff bases (-CH¼N-) are one of the most important biomolecules in medicinal and pharmaceutical fields. [1][2][3][4][5] Some examples of bioactive Schiff bases linked with heterocyclic moiety are Schiff base A bearing benzimidazole, furan and thiadiazole moieties showed a potential antibacterial activity against the three bacterial strains (Staphylococcus aureus, Escherichia coli, and Bacillus pumilus) [6] and Schiff base B bearing 1, 3, 4-thiadiazole with 1, 2, 4-triazol-3-thione showed antituberculosis activity and acetylcholinesterase inhibition effect. [7] Also, Schiff base C which bearing 1, 3, 4-oxadiazole moiety showed inhibitor of a-glucosidase. ...
A series of Schiff bases linked with heterocyclic moiety (6a–c, 7a–c, 11a–c, 12a–c, and 13a–c) and ferrocenyl Schiff bases (15a–c) were designed, synthesized, and confirmed based on the spectral data. Also, evaluations of their in vitro antibacterial and antifungal activities were performed and some Schiff bases (7a, 13a, b, and 15b) show moderate activities. Moreover, the physicochemical, pharmacokinetic, lipophilicity properties, druglikeness, ADME prediction, and toxicity properties of the newly Schiff bases (6a–c, 7a–c, 11a–c, 12a–c, and 13a–c) were predicted in silico. The results exhibited that some Schiff bases agree with druglikeness rules, inhibition of some CYP isoenzymes, and predicted as negative values on the carcinogenicity test. Also, all the Schiff bases exhibited more than 70% on the human intestinal absorption test, moderate permeation on the in vitro Caco-2 cell permeability test, and low permeability on the in vitro MDCK cell permeability test.
... The effects of copper, copper oxide nanoparticles, and copper chelate have been evaluated not only on cancer cells but also on macrophages (88,119). Chatterjee et al., discovered a novel copper chelate, copper N-(2-hydroxy acetophenone) glycinate (CuNG), able to reprogram TAMs in a proinflammatory type which in turn converts Treg and Th2 cells in anti-tumorigenic Th1 cells (120)(121)(122). This compound triggers in TAMs ROS-mediated activation of MAPKs and ERK1/2 pathways which lead to upregulation of IL-12 and simultaneous downregulation of TGF-β and IL-10 production (121). ...
Metal ions, such as selenium, copper, zinc, and iron are naturally present in the environment (air, drinking water, and food) and are vital for cellular functions at chemical, molecular, and biological levels. These trace elements are involved in various biochemical reactions by acting as cofactors for many enzymes and control important biological processes by binding to the receptors and transcription factors. Moreover, they are essential for the stabilization of the cellular structures and for the maintenance of genome stability. A body of preclinical and clinical evidence indicates that dysregulation of metal homeostasis, both at intracellular and tissue level, contributes to the pathogenesis of many different types of cancer. These trace minerals play a crucial role in preventing or accelerating neoplastic cell transformation and in modulating the inflammatory and pro-tumorigenic response in immune cells, such as macrophages, by controlling a plethora of metabolic reactions. In this context, macrophages and cancer cells interact in different manners and some of these interactions are modulated by availability of metals. The current review discusses the new findings and focuses on the involvement of these micronutrients in metabolic and cellular signaling mechanisms that influence macrophage functions, onset of cancer and its progression. An improved understanding of “metallic” cross-talk between macrophages and cancer cells may pave the way for innovative pharmaceutical or dietary interventions in order to restore the balance of these trace elements and also strengthen the chemotherapeutic treatment.
... Schiff bases with widespread pharmacological properties attributed to the azomethine C = N functional group can readily form stable complexes with most of the transition metals providing a variety of properties and biological applications. The literature reports have demonstrated increasing interest in metal complexes of Schiff bases as promising agents in the area of cancer drug discovery due to their potent anti-proliferative activity against a variety of cancer cell lines, tumor growth inhibition in animal models and their role in overcoming multidrug resistance (Ganguly et al., 2014;Li et al., 2017;Niu et al., 2016;Rafi et al., 2016;Shanmugam et al., 2018). ...
Breast cancer is the most frequently diagnosed cancer among women worldwide. Recently, increasing attention has been paid to the anticancer effects of transition metal complexes of indole Schiff bases. β-diiminato Manganese III complex has shown promising cell cycle arrest and apoptosis induction against MCF-7 and MDA-MB-231 breast cancer cells. In this study, time- and dose- dependent inhibitory activity were evaluated using MTT assay after 48 h and 72 h exposure time. In addition, median effect analysis was conducted according to Chou–Talalay method to investigate whether Mn III complex has synergistic effect in combination with chemotherapeutic drugs on inhibiting breast cancer cell growth. The molecular mechanisms underlying its potent antiproliferative effect was determined through bioluminescent caspase-3/7, -8 and -9 activity assays and quantitative expression analysis of cell cycle- and apoptosis-related genes. Furthermore, safety evaluation of Mn III complex was assessed through the acute oral toxicity test in in vivo model. The MTT assay results revealed that it potently reduced the viability of MCF-7 (IC 50 of 0.63 ± 0.07 µg/mL for 48 h and 0.39 ± 0.08 µg/mL for 72 h) and MDA-MB-231 (1.17 ± 0.06 µg/mL for 48 h, 1.03 ± 0.15 µg/mL for 72 h) cells in dose- and time-dependent manner. Combination treatment also enhanced the cytotoxic effects of doxorubicin but not tamoxifen on inhibiting breast cancer cell growth. The involvement of intrinsic and extrinsic pathway in apoptosis induction was exhibited through the increased activity of caspase-9 and caspase-8, respectively, leading to enhanced downstream executioner caspase-3/7 activity in treated MCF-7 and MDA-MB-231 cells. In addition, gene expression analysis revealed that Mn III complex exerts its antiproliferative effect via up-and down-regulation of p21 and cyclin D1, respectively, along with increased expression of Bax/Bcl-2 ratio, TNF-α, initiator caspase-8 and -10 and effector caspase-3 in MCF-7 and MDA-MB-231 cells. However, the results did not show increased caspase-8 activity in treated MCF-7 cells. Furthermore, in vivo acute oral toxicity test revealed no signs of toxicity and mortality in treated animal models compared to the control group. Collectively, the promising inhibitory effect and molecular and mechanistic evidence of antiproliferative activity of Mn III complex and its safety characterization have demonstrated that it may have therapeutic value in breast cancer treatment worthy of further investigation and development.
... Recently, the interest of researchers is attracted by compounds with conjugated double bonds, which have a complex of useful and unique properties [1]. At the same time, the importance and prospects of the use of poly-conjugated compounds in various fields of science and technology (organic electronics [2], biomedicine [3], textile [4], and rubber industry [5]) demonstrates that the potential of this class of compounds is far from exhausted. Therefore, the question of design of new structures of polymers with conjugated systems with special properties (high luminescence, increased electrical conductivity, manufacturability) is very promising and relevant. ...
Oxidative polymerization of benzylidenephenylenediamines produced polymers containing conjugated double bonds. Kinetic studies of the processes of oxidative polymerization of benzylidenephenylene diamines were carried out. The obtained kinetic dependencies allowed us to suggest the mechanism of oxidative polymerization of benzylidenephenylenediamines, which flows through the stage of formation of the cation radical, dimmer, tetramer, leading eventually to the formation of the polymer. In this case the limiting stadia is the formation of cation-radical, and chain growth occurs by N-C. A study of the thermal properties of the polymers showed that polybenzylidenephenylenediamines is characterized by rather high values of heat resistance. It was found that the process of destruction of most of the synthesized polymers occurs in several stages and depends on the chemical structure of the macromolecule.
... This is due to the complex properties which these connections have [1]. Herewith, the importance and prospects of using azomethine compounds in various fields of science and technology (organic electronics [2], Biomedicine [3], textile [4], rubber industry [5]) demonstrates that the potential of this class of compounds is far from being exhausted. Therefore, the question of finding new structures of azomethine compounds with special properties (high luminescence, increased electrical conductivity, solubility in organic solvents) is very promising and relevant. ...
Oxidative polymerization of 3-amino,2'-,(3')-nitrodiphenylazomethine was carried out in various ways. A possible mechanism for the polymerization of 3-amino,2'-,(3')- nitrodiphenylazomethine, where chain growth occurs as type N-C, is shown. It has been found that the yield of the polymer product is affected by the polymerization process and time. The chemical structure of the polymers obtained is established. The study of the thermal properties of polymers showed a low thermal stability and the process of destruction proceeds in two stages.
... Copper (II) complexes are generally found to be effective antimicrobials and also antitumor drugs (Kalaivani et al., 2017) All these facts clearly indicate that copper (II) complexes can be accepted as a promising alternative for platinum-based drugs. Already many copper(II) Schiff base complexes have been evaluated for their effective anticancer drugs (Ganguly, Chakraborty, Banerjee, & Choudhuri, 2014;Ganguly, Chakraborty, Banerjee, and Choudhuri, 2012;Ganguly et al., 2011;Lakowicz and Weber, 2016;Tjioe, Meininger, Joshi, Spiccia, & Graham, 1984;Wang, Zhang, Zhang, Tao, & Tang, 1990). ...
Two novel copper (II) substituted thiosemicarbazone Schiff base complexes [Cu(L1)(µ-SCN)]n(NO3)2 (1) and [Cu2(µ-SCN)(SCN)(L2)2](NO3) (2) have been synthesized by condensing substituted thiosemicarbazides like 4-methyl-3-thiosemicarbazide or 4-ethyl-3-thiosemicarbazide with 2-acetylpyridine. Both the metal complexes 1 and 2 are characterized using different spectroscopic techniques like IR, UV-Vis, ESR spectroscopy followed by elemental analysis, cyclic voltammetric measurement and single crystal X-ray structure analysis. X-ray crystal structure analysis reveal that complex 1 is polymeric while complex 2 is dimeric in nature. The coordination geometry around Cu(II) are square pyramidal in which thiosemicarbazone Schiff base ligand coordinate to the central Cu(II) atom in tridentate fashion. The prominent interaction patterns of 1 and 2 with CT-DNA were examined by employing electronic absorption and emission spectral titrations, cyclic voltammetry and viscosity measurements. All the results show that CT-DNA binds with both copper (II) complexes 1 and 2. Furthermore, protein binding ability in vitro of complexes 1 and 2 with both BSA and HSA were carried out using multispectroscopic techniques and a static quenching pattern was observed in both cases. Molecular docking study was employed to ascertain the exact mechanism of action of 1 and 2 with DNA and protein molecules (BSA and HSA). In vitro cytotoxicity activity of complexes 1 and 2 toward AGS and A549 was evaluated using MTT assay which demonstrates that both complexes 1 and 2 have superior prospectus to act as anticancer agents.
Communicated by Ramaswamy H. Sarma
