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In vitro Cytotoxic Activity of β-chalcogen-substituted Michael-aldol Type Adducts Against Hela and RKO Cell Lines
Abstract
There is a lack of biological studies using selenium and tellurium compounds, specially concern with cancer therapy. The aim of this study is to evaluate the cytotoxicity action of nine β-chalcogen-substituted Michael-aldol-type adducts on HeLa and RKO cancer cell lines. The cytotoxic effect was assessed by MTT assay and was performed in HeLa and RKO cell lines cultured in RPMI-1640 medium in (95% O2+5% CO2) at 37°C. The IC50 values demonstrated that all compounds presented cytotoxic effect in 17-100 μM range. The compounds 1 and 5 presented cytotoxic effect in 17 -40 μM range to HeLa cells. In RKO cells compounds 2-5, 7 and 8 presented cytotoxicity between 46 -58 μM. Compound 1 presented cytotoxicity for HeLa cells similar to those found to etoposide (11.35±2.73 μM; p>0.05) and none of the compounds presented this similarity for RKO cells. It is important to notice that the compounds presented cell line selectivity: compound 1 to HeLa and compounds 7 and 8 to RKO cells. The RKO cells were more sensitivity to tellurites, which were not effective to HeLa cells. In conclusion, the compound 1 presented promissory anticancer potential and the cytotoxic specificity of tellurides for RKO cells demonstrated that there is an important biological role based on this chemical element.
... • Papillary lung adenocarcinoma: Although it is a rare type of lung cancer, the occurrence can cause themalignant cells of the tumor form to complex papillary structures exhibiting proliferative, destructive growth affecting normal lung tissue. [7][8][9][10][11][12] • Mixed subtype: Mixed lung adenocarcinoma subtype is categorized by the occurrence of a mixed array of different patterns (papillary, acinar, bronchioloalveolar, solid with mucin). This type of adenocarcinomais difficult to treat by chemotherapy. ...
Non-small cell lung cancer is a type of lung cancer, where healthy cells in the lungs grow out of control forming a tumor or a nodule. Although small cell lung cancer and non-small cell lung cancer share few common symptoms and causes, their rate of spread or metastasis differs significantly. Targeted gene therapies involving uses of targeted drugs against specific gene or protein are increasingly being used for the treatment of lung cancer. This study aims at understanding the efficacy of the bioactive compounds over the already existing chemotherapy drug- Gemcitabine. For this study, the target receptor proteins of Non-Small Cell Lung Cancer (NSCLC) were retrieved from Protein Data Bank (PDB) and the ligand compounds were retrieved using PubChem NCBI. Based on various research studies, four target proteins from NSCLC and sixteen bioactive compounds of Curculigoorchioides (Black musale) were selected. And their effect of bioactive compounds has been studied by means of in-silico approach and further the identified potential active compounds have been compared with control. This comparative in-silico study has predicted that the bioactive principle of Curculigoorchioides has better efficacy against cancer receptors and can considered as an effective alternative drug for cancer treatment. Concluding, the present study will be useful in future for designing novel therapeutic plant-based drug with higher efficacy for the treatment of lung cancer.
... Caco-2 and HT29 are the most commonly used cell models (Kotake-Nara et al., 2015;Kotake-Nara, Yonekura, & Nagao, 2010;O'Sullivan, Aherne, & O'Brien, 2009;Park et al., 2005). Meanwhile, due to the differentiation and secretion characteristics of intestinal epithelial cells, other intestinal source cells, including HCT116 (Borralho, Kren, Castro, Moreira, & Rodrigues, 2009), HCT8 (Wang et al., 2008), LS 174T (Bu, Li, Tian, & Huang, 2011), LOVO (Bhatia, Saini, & Falzon, 2009) (Paolo et al., 2000), DLD-1 (Akao et al., 2011), RKO (Leticia et al., 2013), CW-2 (Higuchi et al., 1999) and Hce-8693 (Ma et al., 2003), might also be used in the future. Cellular models have been widely employed in the study of carotenoids bioaccessibility, such as to evaluate bioaccessibility and the uptake of carotenoids derived from specific food substrates (Rošul, Đerić, Mišan, Pojić, Š imurina, Halimi, Nowicki, Cvetković, Mandić, & Reboul, 2022) and to clarify the mechanism by which specific components interfere with the gastrointestinal absorption of carotenoids Kotake-Nara & Nagao, 2012). ...
The published literature has shown that there are various evaluation methods for the process of carotenoids digestion and absorption. However, it was found that many concepts are ambiguous in the evaluation process, and the selection of evaluation methods is inappropriate and inaccurate. These deficiencies trouble readers, hamper comparisons among different studies, and generate controversy in different literature. Therefore, it is imperative to establish a complete and standardized system for evaluating the digestion and absorption process of carotenoids. This review begins by clarifying confusing concepts during the process of carotenoids digestion and absorption, including the release rate, micellization rate, bioaccessibility, relative bioavailability and absolute bioavailability. Then this review discusses relevant factors affecting the key process of the digestion and absorption of carotenoids. Finally, a more specific and standardized system for evaluating carotenoids bioavailability was suggested based on four dimensions: intake, digestion, absorption and metabolic process. Clarifying concepts such as digestion and absorption and standardizing corresponding research methods will help to obtain reliable data and support interoperability and comparisons across studies.
... The current known therapies are based on radio and chemotherapies and although in many cases, the patients have their health re-established, the treatment is very painful since their immunological system is severely compromised, because these procedures are not cells selective. [1] Substantial advances have been made in understanding the key roles of receptor tyrosine kinase (RTK) in the signalling pathways that govern fundamental cellular processes, such as proliferation, migration, metabolism, differentiation and survival. In the normal cells RTK activity is tightly controlled.When they are mutated or structurally altered, they become potent oncoproteins which leads to abnormal activation of RTKs in transformed cells has been shown to be causally involved in the development and progression of many human cancers. ...
Vitex negundo Linn.[Verbenaceae], commonly known as Five-leaved Chaste tree or Monk’s Pepper (Hindi —Sambhalu, Nirgundi) is used as medicine fairly throughout the greater part of India. The aim of present study is to isolate negundoside and evaluate anticancer activity by in vitro and in silico method. Negundoside was isolated by column chromatography from ethyl acetate fractionation of methanol extract of leaves of V.negundo. Negundoside was characterized by UV,IR, 1H-NMR, 13C-NMR and Mass spectrum. Standardization of negundoside was done by HPTLC fingerprinting. In vitro anticancer activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 20-100 μg/ml and in silico docking studies using enzyme EGFR tyrosine kinase. Fingerprinting of isolated negundoside were done by HPTLC method. The IC50 value was found to be 62.69 μg/ml in in vitro anticancer activity in HeLa Cell lines. Negundoside was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown -7.32 kJ mol-1 binding and -11.32 kJ mol-1 docking energy with five hydrogen bonds. Negundoside has shown to possess anticancer activity both in vitro and in silico studies.
... Cancer is one of the highest impacting diseases worldwide with significant morbidity and mortality rates. The current known therapies are based on radio and chemotherapies and although in many cases, the patients have their health re-established, the treatment is very painful since their immunological system is severely compromised, because these procedures are not cells selective [1].Substantial advances have been made in understanding the key roles of receptor tyrosine kinase (RTK) in the signalling pathways that govern fundamental cellular processes, such as proliferation, migration, metabolism, differentiation and survival. In the normal cells RTK activity is tightly controlled. ...
Background: Rubia cordifolia Linn.[ Rubiaceae], commonly known as Indian Maddar and Manjistha, is used as medicine for treatment of various ailments in Traditional System of Medicine of India. Purpose: To isolate rubiadin and evaluate in vitro antiproliferative activity and in silico method. Material and Methods: Rubiadin was isolated from the roots of R.cordifolia. Rubiadin was characterized by IR, 1H-NMR, 13C-NMR and Mass spectrum. Standardization of rubiadin was done also by HPLC fingerprinting. In vitro antiproliferative activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 20-100 μg/ml in triplicate and in silico docking studies using enzyme EGFR tyrosine kinase. Results: Fingerprinting of isolated rubiadin were done by HPLC method. The IC50 value was found to be 56.63 ± 0.025 μg/ml in in vitro antiproliferative activity in HeLa cell lines. Rubiadin was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown -7.07 kJ mol-1 binding and -7.12 kJ mol-1 docking energy with two hydrogen bonds. Conclusion: Rubiadin has shown to possess in vitro antiproliferative activity and in silico studies.
... Cancer is one of the highest impacting diseases worldwide with significant morbidity and mortality rates. The current known therapies are based on radio and chemotherapies and although in many cases, the patients have their health re-established, the treatment is very painful since their immunological system is severely compromised, because these procedures are not cells selective [Leticia et al. 2013]. Substantial advances have been made in understanding the key roles of receptor tyrosine kinase (RTK) in the signalling pathways that govern fundamental cellular processes, such as proliferation, migration,metabolism, differentiation and survival. ...
Piper nigrum [Piperaceae], commonly known as black pepper is used as medicine fairly throughout the greater part of India and as a spice globally.
To isolate piperine and evaluate in vitro cytotoxic [antiproliferative] activity and in silico method.
Piperine was isolated from the fruits of P.nigrum. Piperine was characterized by UV,IR, 1 H-NMR, 13 C-NMR and Mass spectrum. Standardization of piperine was done also by HPTLC fingerprinting. In vitro cytotoxic activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 20 to 100 μg/ml in triplicate and in silico docking studies using enzyme EGFR tyrosine kinase.
Fingerprinting of isolated piperine were done by HPTLC method. The IC 50 value was found to be 61.94 ± 0.054 μg/ml in in vitro cytotoxic activity in HeLa Cell lines. Piperine was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown −7.6 kJ mol −1 binding and 7.06 kJ mol −1 docking energy with two hydrogen bonds.
piperine has shown to possess in vitro cytotoxic activity and in silico studies.
... Cancer is one of the highest impacting diseases worldwide with significant morbidity and mortality rates. The current known therapies are based on radio and chemotherapies and although in many cases, the patients have their health re-established, the treatment is very painful since their immunological system is severely compromised, because these procedures are not cells selective [1]. Substantial advances have been made in understanding the key roles of receptor tyrosine kinase (RTK) in the signalling pathways that govern fundamental cellular processes, such as proliferation, migration, metabolism, differentiation and survival. ...
Glycyrriza glabra Linn.[ Fabaceae], commonly known as yashtimadhu, mulhatti, is used as medicine for treatment of various aliments in Traditional System of Medicine fairly throughout the greater part of India. In the present study, we have evaluated anticancer activity of Ammonium glycyrrhizinate by in vitro and in silico method. Ammonium glycyrrhizinate was isolated from roots of G.glabra and was characterized by solubility, melting point, infrared (IR) and thin layer chromotography (TLC) pattern. In vitro anticancer activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 100-500 µg/ml using microtitre plate assays by ELISA and in silico docking studies using enzyme EGFR tyrosine kinase. The IC 50 value was found to be 282.45 µg/ml in in vitro anticancer activity in HeLa cell lines. Ammonium glycyrrhizinate was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown-11.03 kJ mol-1 binding and-12.47 kJ mol-1 docking energy with five hydrogen bonds. We can conclude that ammonium glycyrrhizinate has shown to possess anticancer activity both in vitro and in silico studies.
... Cancer is one of the highest impacting diseases worldwide with significant morbidity and mortality rates. The current known therapies are based on radio and chemotherapies and although in many cases, the patients have their health re-established, the treatment is very painful since their immunological system is severely compromised, because these procedures are not cells selective [1]. Substantial advances have been made in understanding the key roles of receptor tyrosine kinase (RTK) in the signalling pathways that govern fundamental cellular processes, such as proliferation, migration, metabolism, differentiation and survival. ...
Abstract: Glycyrriza glabra Linn.[ Fabaceae], commonly known as yashtimadhu, mulhatti, is used as medicine for treatment of various aliments in Traditional System of Medicine fairly throughout the greater part of India. In the present study, we have evaluated anticancer activity of Ammonium glycyrrhizinate by in vitro and in silico method. Ammonium glycyrrhizinate was isolated from roots of G.glabra and was characterized by solubility, melting point, infrared (IR) and thin layer chromotography (TLC) pattern. In vitro anticancer activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 100-500 μg/ml using microtitre plate assays by ELISA and in silico docking studies using enzyme EGFR tyrosine kinase. The IC50 value was found to be 282.45 μg/ml in in vitro anticancer activity in HeLa cell lines. Ammonium glycyrrhizinate was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown -11.03 kJ mol-1 binding and -12.47 kJ mol-1 docking energy with five hydrogen bonds. We can conclude that ammonium glycyrrhizinate has shown to possess anticancer activity both in vitro and in silico studies.
The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound. In addition, molecular docking revealed that benzo[h]quinolines can correctly dock into the hydrophobic pocket of the targets receptor protein aromatase and CDK2, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. These findings reveal that benzo[h]quinolines act as anti-cancer agents by inducing oxidative stress-mediated DNA damage.
In this paper the preparation of reactive organometallics starting from organotellurides is reviewed. The application of the reactive organometallics prepared in this way in the synthesis of bioactive compounds is commented.
n‐Butanethiol is generated in situ by sequential addition of n‐butyllithium and water to elemental sulfur. The n‐butanethiol formed was reacted with electron‐deficient olefines to give Michael‐type addition products in good yields. The method avoids the manipulation of the bad‐smelling n‐butanethiol.
This paper describes a surface‐enhanced Raman scattering (SERS) systematic investigation regarding the functionalization of gold (Au) and silver (Ag) nanoparticles with diphenyl dichalcogenides, i.e. diphenyl disulfide, diphenyl diselenide, and diphenyl ditelluride. Our results showed that, in all cases, functionalization took place with the cleavage of the chalcogen–chalcogen bond on the surface of the metal. According to our density functional theory calculations, the molecules assumed a tilted orientation with respect to the metal surface for both Au and Ag, in which the angle of the phenyl ring relative to the metallic surface decreased as the mass of the chalcogen atom increased. The detected differences in the ordinary Raman and SERS spectra were assigned to the distinct stretching frequencies of the carbon–chalcogen bond and its relative contribution to the ring vibrational modes. In addition, the SERS spectra showed that there was no significant interaction between the phenyl ring and the surface, in agreement with the tilted orientation observed from our density functional theory calculations. The results described herein indicate that diphenyl dichalcogenides can be successfully employed as starting materials for the functionalization of Au nanoparticles with organosulfur, organoselenium, and organotellurium compounds. On the other hand, diphenyl disulfide and diphenyl diselenide could be employed for the functionalization of Ag nanoparticles, while the partial oxidation of the organotellurium unit could be detected on the Ag surface. Copyright © 2011 John Wiley & Sons, Ltd.
MoritaBaylisHillman derivatives have been extensively investigated as intermediates in the preparation of important classes of compounds. However, there are intrinsic limitations regarding the structure of the Michael electrophile acceptors, the aldehydes, and the catalysts. Therefore, this transformation has several drawbacks, including, for example, its long reaction times. Herein we present a simple, general, fast, and high-yielding protocol for the one-pot synthesis of MoritaBaylisHillman derivatives. Our approach is driven by a lithium selenolate Michael/aldol operation with concomitant O-functionalization/selenoxide elimination cascade sequences.
The naturally occurring butanolides (−)-blastmycinolactol, (+)-blastmycinone, (−)-NFX-2, (+)-antimycinone as well as the four stereoisomers of the butenolide Acaterin were prepared in high enantiomeric purity using hydroxy-vinyl tellurides as starting materials.
Reaction of organotellurides with easily available organometallics leads to a fast and clean tellurium/metal exchange reaction, allowing the preparation of a range of functionalized organometallics with C-sp 3 , C-sp 2 , and C-sp hybridization carbanionic centers. Some synthetic applications of the tellurium/metal exchange reactions are discussed.
Diphenyl ditelluride (DPDT) and tellurium tetrachloride (TeCl(4)) were evaluated for toxicity in transformed (HT-29, Caco-2) and non-transformed colon cells (CCD-18Co). Significant decreases in viability were observed with DPDT exposure in HT-29 (62.5-1000μM), Caco-2 (31.25-1000μM) and CCD-18Co cells (500-1000μM) and with TeCl(4) in HT-29 (31.25-1000μM), Caco-2 (31.25-1000μM) and CCD-18Co cells (500-1000μM). Light microscopy confirmed viability analysis. Significant increases in caspase 3/7 and 9 activity were observed with DPDT in HT-29 (500-1000μM) and CCD-18Co cells (1000μM) indicating apoptosis. No significant increases in caspases were seen with TeCl(4) indicating necrosis. Apoptosis or necrosis was confirmed with fluorescent staining (FITC-Annexin, Hoechst 33342 and Ethidium Homodimer). Significant decreases in GSH/GSSG ratio were observed with DPDT in HT-29 (62.5-1000μM), and CCD-18Co cells (1000μM) and with TeCl(4) in HT-29 (62.5-1000μM) and CCD-18Co cells (250-1000μM). We concluded that cells treated with DPDT resulted in apoptosis and TeCl(4) treatment in necrosis. GSH/GSSG ratio shifts indicate oxidative mechanisms are involved.
Our randomized controlled trial previously demonstrated improved staging accuracy with targeted nodal assessment and ultrastaging (TNA-us) in colon cancer (CC). Our objective was to test the hypothesis that TNA-us improves disease-free survival (DFS) in CC.
In this randomized trial, targeted nodal assessment and ultrastaging resulted in enhanced lymph node diagnostic yield associated with improved staging accuracy, which was further associated with improved disease-free survival in early colon cancer.
Clinical parameters of the control (n = 94) and TNA-us (n = 98) groups were comparable. Median (interquartile range) lymph node yield was higher in the TNA-us arm: 16 (12-22) versus 13 (10-18); P = 0.002. Median follow-up was 46 (29-70) months. Overall 5-year DFS was 61% in the control arm and 71% in the TNA-us arm (P = 0.11). Clinical parameters of node-negative patients in the control (n = 51) and TNA-us (n = 55) groups were comparable. Lymph node yield was higher in the TNA-us arm: 15 (12-21) versus 13 (8-18); P = 0.03. Five-year DFS differed significantly between groups with node-negative CC (control 71% vs TNA-us 86%; P = 0.04). Survival among stage II CC alone was higher in the TNA-us group, 83% versus 65%; P = 0.03. Adjuvant chemotherapy use was nearly identical between groups. TNA-us stratified CC prognosis; DFS differed significantly between ultrastaged and conventionally staged node-negative patients [control pN0 72% vs TNA-us pN0(i-) 87%; P = 0.03]. Survival varied according to lymph node yield in patients with node-negative CC [5-year DFS: <12 lymph nodes = 57% vs 12+ lymph nodes = 85%; P = 0.011] but not in stage III CC.
TNA-us is associated with improved nodal diagnostic yield and enhanced staging accuracy (stage migration), which is further associated with improved DFS in early CC. This study is registered at clinicaltrials.gov under the registration number: NCT01623258.
In the search for molecules with potential antiangiogenic activity we found that several imidoselenocarbamate derivatives, which have pro-apoptotic and antiproliferative activities, under hypoxic conditions release methylselenol, a volatile and highly reactive gas that was considered to be responsible for the observed biological activity. The kinetic for the liberation of methylselenol is highly dependent on the nature of the overall structure and correlate with their proven pro-apoptotic activity in lung cancer cell line H157. The preliminary structure-activity relationships allow us to select as the basic structural element a scaffold constructed with an imidoselenocarbamate fragment decorated with a methyl residue on the Se central atom and two heteroaromatic lateral rings. These imidoselenocarbamate derivatives may be of interest both for their antitumoral activities and because they have a structure that can be considered as a template for the design of new derivatives with apoptotic activity. This activity is related to the controlled delivery of methylselenol and makes this an interesting approach to develop new antitumoral agents.