Human Colon Adenocarcinoma Research Articles

Evaluation of Cytotoxic Activity of Loaded Catechin into Iron Oxide Nanoparticles Coated with Sodium Alginate and Hydroxyapatite against Human HT-29 Colon Adenocarcinoma and Breast Cancer MCF-7 Cells

Evaluation of Cytotoxic Activity of Loaded Catechin into Iron Oxide Nanoparticles Coated with Sodium Alginate and Hydroxyapatite against Human HT-29 Colon Adenocarcinoma and Breast Cancer MCF-7 Cells

Exopolysaccharide from Lactococcus hircilactis CH4 and Lactobacillus delbrueckii GRIPUMSK as new therapeutics to treat biofilm pathogens, oxidative stress and human colon adenocarcinoma

Naturally occurring biopolymers like exopolysaccharides (EPS) secreted by lactic acid bacteria (LAB) has gained significant attention as they are cost effective, renewable and safe. In order to prevent the rapid increase in antibiotic resistant bacteria, the EPS of LAB offers novel approach of targeting the antibiotic resistant pathogens by limiting their effects on environment. Accordingly, in this study, the production, purification, characterization and biological properties of exopolysaccharides from Lactococcus hircilactis strain CH4 and Lactobacillus delbrueckii strain GRIPUMSK were performed. The optimization of lactic acid bacterial strains for exopolysaccharide production was done by response surface methodology and changing the carbon sources in the growth media. The carbohydrate and protein of exopolysaccharide 1 were 79.7 % and 8.7 % respectively and exopolysaccharide 2 were 75.2 % and 9.3 % respectively. When compared with the commercial emulsifier sodium dodecyl sulfate, both the exopolysaccharides have shown good emulsifying activity. Both the exopolysaccharides were linear homo-polysaccharide as determined by Fourier transform infrared spectroscopy and Nuclear magnetic resonance spectra. Scanning electron microscopy showed that the exopolysaccharides were porous and capable of holding water. The exopolysaccharides were partially crystalline as confirmed by X-ray diffraction spectra. Exopolysaccharides from L. hircilactis and L. delbrueckii exhibited significant antimicrobial activity against H. pylori, S. flexneri, S. pyogenes, E. faecalis and C. albicans. Both the exopolysaccharides revealed significant 2,2-diphenyl-1-picrylhydrazyl and hydrogen peroxide scavenging ability with the IC50 value of 100 μg/ml and 80 μg/ml respectively. Exopolysaccharides from L. hircilactis and L. delbrueckii at 100 μg/ml showed significant anticancer activity on HT-29 cells with 58.4 % and 58.7 % respectively. These findings proved that exopolysaccharides from the two selected lactic acid bacterial strains could be explored as natural bioactive carbohydrate polymer for biomedical applications.

Total Synthesis of (+)-Muricatetrocin B via a Late-Stage Co-Catalyzed Hartung-Mukaiyama Cyclization.

Convergent total synthesis of (+)-muricatetrocin B, a tetrahydrofuran-containing acetogenin with potent and selective cytotoxicity against the HT-29 human colon adenocarcinoma cell line, was achieved in 13 steps. Our synthesis is highlighted by a late-stage sequential olefin cross-metathesis/Hartung-Mukaiyama cyclization for convergent assembly of the 2,5-trans-substituted tetrahydrofuran ring.

Synthesis, cytotoxicity, antioxidant activity and molecular modeling of new NSAIDs-EBS derivatives

Two series of NSAIDs-EBS derivatives (5a-j and 9a-i) based on the hybridization of nonsteroidal anti-inflammatory drugs (NSAIDs) skeleton and Ebselen moiety were synthesized. Their cytotoxicity was evaluated against five types of human cancer cell lines, BGC-823 (human gastric cancer cell line), SW480 (human colon adenocarcinoma cells), MCF-7 (human breast adenocarcinoma cells), HeLa (human cervical cancer cells), A549 (human lung carcinoma cells). Moreover, the most active compound 5j showed IC50 values below 3 μM in all cancer cell lines and with remarkable anticancer activity against MCF-7 (1.5 μM) and HeLa (1.7 μM). The redox properties of the NSAIDs-EBS derivatives prepared herein were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like assays. Finally, TrxR1 inhibition activity assay and molecular docking study revealed NSAIDs-EBS derivatives could serve as potential TrxR1 inhibitor.

Probiotic Potential, Antibacterial, and Antioxidant Capacity of Aspergillus luchuensis YZ-1 Isolated From Liubao Tea.

Aspergillus fungi are widely used in the traditional fermentation of food products, so their safety risks and functions are worthy of investigation. In this study, one Aspergillus luchuensis YZ-1 isolated from Liubao tea was identified based on phylogenetic analyses of sequences of three genes coding for internal transcribed spacer 1 (ITS1), β-tubulin (benA), and calmodulin (CaM). The results of hemolytic activity, DNase activity, cytotoxicity assay, and antibiotic resistance assay indicated that the strain is potentially safe. The excellent gastrointestinal fluid tolerance, acid tolerance, bile tolerance, auto-aggregation, co-aggregation, cell surface hydrophobicity, and adhesion to human colon adenocarcinoma (HT29) cell line were observed on analysis of the probiotic properties. Furthermore, the results of the antibacterial activity of A. luchuensis YZ-1 indicated that the strain had strong antagonistic effects against Gram-negative and Gram-positive bacteria as well as fungi. Simultaneously, the water extracts and 80% ethanolic extracts of A. luchuensis YZ-1 cells also showed strong ABTS, DPPH, and OH- scavenging ability. Taken together, our results suggest that A. luchuensis YZ-1 has desirable functional probiotic properties and can be proposed as a biocontrol agent in the food industry.

Evaluation of Cytotoxicity of Gold Glyconanoparticles of Human Colon Adenocarcinoma Cells

INTRODUCTION: Use of metal nanoparticles is a promising trend in oncotherapy.
 AIM: To evaluate cytotoxicity of gold nanoparticles (GNPs) modified with fucose, lactose and galactose residues, on Caco-2 cells.
 MATERIALS AND METHODS: Cells were cultured to a monolayer with GHPs in concentrations of 10 g/ml600 g/ml for particles with fucose, 10 g/ml900 g/ml for particles with lactose and 10 g/ml550 g/ml for particles with galactose. As non-tumor cells, Caco-2 cells were used after differentiation into small-intestine enterocytes (incubation time 21 days). The cytotoxicity of GNPs was evaluated in MTT-test after incubation with cells for 2 hours, 8 hours and 24 hours. A comparison drug was fluorouracil in concentrations of 50 g/ml2000 g/ml. The half-maximal inhibitory concentration (IC50) was calculated in GraphPad Prism 8.4.3 program.
 RESULTS: IC50 for GNPs with fucose for tumor cells was 582 29 and 336 36 g/ml after incubation for 2 hours and 8 hours, respectively; for GNPs with lactose 769 50 and 515 45 g/ml, for GNPs with galactose 467 299 and 299 28 g/ml. For differentiated cells, IC50 for all types of GNPs was higher than for tumor cells after incubation for 2 and 8 hours: for particles with fucose 530 3 and 410 15 g/ml; for particles with lactose 831 7 and 639 14 g/ml; for particles with galactose 511 21 (p = 0.018) and 376 36 g/ml, respectively. After 24-hour incubation of Caco-2 cells with fucose, IC50 did not differ for tumor and differentiated varieties. For other GNPs, IC50 for tumor cells was higher than for differentiated cells. Fluorouracil showed cytotoxicity for tumor cells with IC50 2108 19 and 1764 193 g/ml after 2 hours and 8 hours of incubation, respectively. For differentiated cells, IC50 of fluorouracil was 1694 102 g/ml after 2-hour incubation and 1694 102 g/ml after 8-hour incubation. There were no differences between IC50 of fluorouracil for differentiated and tumor cells with equal incubation time.
 CONCLUSION: GNPs with fucose, lactose and galactose have a cytotoxic effect on human colon adenocarcinoma cells and in the activity are superior to fluorouracil.

An isonicotinohydrazide based fluorescence sensor for detection of Zn2+ in biological systems: Experimental and theoretical studies along with cell imagine

Zinc ions (Zn2+) play a significant role in our daily lives and production, which is related to human health and environment protection. Therefore, it is crucial in this field to develop sensors with improved analyte selectivity and sensitivity. We prepared a fluorescent sensor, DIH, through the reaction of 5-(tert-butyl)-2-hydroxyisophthalaldehyde with isonicotinohydrazide. DIH, in free form, can undergo excited state intramolecular proton transfer (ESIPT) process upon excitation. Among a wide range of metal ions tested, only Zn2+ inhibited this ESIPT process, resulting in an increase in fluorescence intensity (13.3-fold) with chelation enhancement fluorescence process (CHEF). The complex (DIH/Zn2+) stoichiometry was determined to be 1:1 and the binding constant of the complex was estimated as 3.18 × 107 M−1. DIH could also be applied to detect zinc ions down to a low concentration level of 11.2 nanomolar with fluorescence spectroscopy. Moreover, the cytotoxicity evaluation of DIH against human colon adenocarcinoma cells lines demonstrated that the sensor was nontoxic and could be used successfully in cellular imaging.

Favorable Antitumor Activity of Citrus microcarpa B. on Human Colon Adenocarcinoma Tumor Xenografted in Immunosupressed Mice.

The antitumor activity of Citrus microcarpa B. on HT29 human colon adenocarcinoma tumors xenografted in immunosuppressed mice was determined in this study. The objective of the study was to determine if the crude extract of C. microcarpa B. exhibited antitumor activity against HT29 human colon adenocarcinoma tumors xenografted in immunosuppressed mice. Cyclosporine-induced immunosuppressed mice were injected subcutaneously with 106 HT29 cells in the caudo-dorsal area of the back near the base of the tail to induce tumor growth. Tumors were grown for 9 days, and the mice were then administered with C. microcarpa B. (160 and 630 mg/kg) (Group A; n = 4 and B; n = 4) and normal saline solution (Group C; n = 4) intraperitoneally. Tumor volume was measured to assess the change in tumor volume after 24, 48, and 72-hour post-treatment administration. Tumors were then excised and analyzed histopathologically to evaluate the ratio of necrotic area to viable cancer cells in the tumors. Treatment of C. microcarpa B. with a dose of 160 mg/kg (P=0.002) and 630 mg/kg produced a significant decrease in tumor volume with the significance only observed at 72 hours post-treatment. Histopathological analysis showed a considerable decrease in the area of necrosis against viable tumor cells in the treatment of C. microcarpa B. with a dose of 630 mg/kg. It can thus be said that C. microcarpa B. is effective in reducing tumor volume, specifically at a dose of 630 mg/kg 72-hours post-treatment.

Curcumin or quercetin loaded nutriosomes as oral adjuvants for malaria infections

Artemisinin, curcumin or quercetin, alone or in combination, were loaded in nutriosomes, special phospholipid vesicles enriched with Nutriose FM06®, a soluble dextrin with prebiotic activity, that makes these vesicles suitable for oral delivery. The resulting nutriosomes were sized between 93 and 146 nm, homogeneously dispersed, and had slightly negative zeta potential (around −8 mV). To improve their shelf life and storability over time, vesicle dispersions were freeze-dried and stored at 25 °C. Results confirmed that their main physico-chemical characteristics remained unchanged over a period of 12 months. Additionally, their size and polydispersity index did not undergo any significant variation after dilution with solutions at different pHs (1.2 and 7.0) and high ionic strength, mimicking the harsh conditions of the stomach and intestine. An in vitro study disclosed the delayed release of curcumin and quercetin from nutriosomes (∼53% at 48 h) while artemisinin was quickly released (∼100% at 48 h). Cytotoxicity assays using human colon adenocarcinoma cells (Caco-2) and human umbilical vein endothelial cells (HUVECs) proved the high biocompatibility of the prepared formulations. Finally, in vitro antimalarial activity tests, assessed against the 3D7 strain of Plasmodium falciparum, confirmed the effectiveness of nutriosomes in the delivery of curcumin and quercetin, which can be used as adjuvants in the antimalaria treatment. The efficacy of artemisinin was also confirmed but not improved. Overall results proved the possible use of these formulations as an accompanying treatment of malaria infections.

Biosynthesis of silver nanoparticles from Arum dioscoridis plant leaf aqueous extract: anticancer and antimicrobial properties

This study was carried out to synthesize silver nanoparticles (AgNPs) from Arum dioscoridis (AD) leaf extract and to investigate the cytotoxic and antipathogenic effects of them. The plant material had a reducing and stabilizing effect on the synthesized nanomaterial. During the plant-mediated synthesis of nanomaterials, no substances that would cause environmental pollution were used. For the structural characterization of AD-AgNPs, Ultraviolet-visible (UV-vis) Spectroscopy, Field Emission Scanning Electron Microscopy (FE-SEM), Electron Dispersive X-ray (EDX) Spectroscopy, Fourier Transform Infrared (FT-IR) Spectroscopy, Transmission Electron Microscopy (TEM), X-ray Diffractometer (XRD), Atomic Force Microscopy (AFM) and Zetasizer analyses were performed. The produced AgNPs showed maximum surface plasmon resonance at 431.67 nm and had mostly spherical morphology. The zeta potential value of the nanomaterial was -9.76 mV and the average powder crystal size was 31.48 nm. The minimum inhibitory concentration (MIC) values (mg/L) of AD-AgNPs on Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Candida albicans were 0.25, 2.00, 0.125, 4.00, and 1.00, respectively. After 24 and 48 hours of application by MTT [3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromid] assay, the half-maximal inhibitory concentrations (IC50: μg/mL) of AD-AgNPs on human colon adenocarcinoma cell (CACO-2), human breast cancer cell (MCF-7), glioblastoma multiforme cell (T98-G), and healthy human umbilical vein endothelial cell (HUVEC) lines were determined as 2.977, 2.801, 5.694, 4.392; 2.115, 2.300, 2.612, 4.091, respectively.

A study on synthesis, antioxidant, anticancer activities and docking study of novel benzimidazoloyl thiazole derivatives

2-(Substituted-amino)-5-(1-methylbenzimidazol-2-oyl)thiazoles have been synthesized by the reaction of 2-(2-bromoacetyl)-1-methylbenzimidazole and 1-(substituted-amino)-3-(N,N-dimethylimidoyl)thioureas in the presence of triethyl amine. The structure of the newly synthesized benzmidazoloyl thiazole analogues have been confirmed by spectroscopic techniques. The in vitro antioxidant activity has been studied using DPPH assay and anticancer activity has been studied using MTT assay against human colon adenocarcinoma cells. In silico studies have been performed to predict the binding modes of the compounds with the cyclin-dependent kinase protein 5FGK. It is evident from the current results that all the synthesized compounds exhibit remarkable antioxidant and anticancer potential.

Herniarin-loaded solid lipid nanoparticles: promising molecular mechanism and therapeutic potential against pancreatic cancer line.

The notion of cancer therapy is intrinsically subjected to multiple challenges due to the drug resistance and drug toxicity for normal tissues. Herniarin (7-methoxycoumarin) belongs to the naturally occurring aromatic phytochemicals and coumarins. Considering the boosting effect of nanocarriers in drug delivery, we investigated the proapoptotic, anti-metastatic properties, and molecular mechanism of herniarin-loaded solid lipid nanoparticles on human gastric adenocarcinoma (AGS), human colon adenocarcinoma (HT-29), human pancreatic carcinoma (Panc-1), and normal human skin fibroblast (HFF) cell lines. The cytotoxicity of synthesized nanoparticle have been tested using MTT assay. The obtained results manifested that concentration of herniarin that exerts 50% cell growth inhibition (IC50) against HT-29, AGS, and Panc-1 was calculated 138.34, 123.46, and 83.744 µL, respectively. Given that nanoparticles showed lowest IC50 values on Panc-1 cell line, these cells were selected for further analysis. The apoptosis induction and cell cycle arrest were examined performing real-time PCR, flow cytometry, and DAPI/acridine orange-propidium iodide staining. The expression of apoptosis-related genes, including BCL-2, was decreased, while the expression of CASP9, CASP8, and CASP3 was increased in response to the treatment. Moreover, the expression of metastasis-related gene (MMP2) was significantly suppressed under Her-SLN-NPs treatment. According to the flow cytometry findings, we observed no cell cycle arrest at any stage. Our funding manifested herniarin encapsulated solid lipid nanoparticles has potent therapeutic target against Panc-1 cell line.

Structural Design of Oleogel‐Hydrogel Bigels for Co‐Delivery of Curcumin and Epigallocatechin Gallate with Synergistic Stability and Bioactivity

AbstractBigels are novel biphasic systems containing hydrogel and oleogel structures, which are designed to deliver multiple bioactives for synergistic activity. The current study develops bigels based on a carrageenan hydrogel and a monoglyceride (GMS) oleogel. Results show that the microstructures of bigels are facilely modified by two surface active ingredients (Tween 20 and polyglycerol polyricinoleate), which then influence the microstructures of the bigels. When curcumin and epigallocatechin gallate (EGCG) are delivered simultaneously, the bioactives work synergistically to slow thermal degradation. Simulated digestion tests indicate that the bigel structures can delay the release of the two bioactives in artificial saliva and simulated gastric fluid (SGF), and allow fast release in simulated intestinal fluid (SIF). DPPH and ABTS tests show the digested Tween 20 bigels containing EGCG and curcumin present synergistic antioxidant activity. Anticancer activity is evaluated in human colon adenocarcinoma HCT116, and the two bioactives work cooperatively to lower cell viability. The bioactives released from Tween 20 bigels have higher cytotoxicity than those from polyglycerol polyricinoleate bigels. The results reveal that facile structural design of bigels has the potential to achieve synergistic stability and bioactivity of co‐delivered bioactives, which is meaningful for the development of functional pharmaceutical, cosmetic, and food products.

Chemical composition of extracts from leaves, stems and roots of wasabi (Eutrema japonicum) and their anti-cancer, anti-inflammatory and anti-microbial activities

The purpose of our study was to evaluate the composition of the extracts obtained from the roots and leaves of Eutrema japonicum cultivated in Poland. For this purpose, LC-DAD-IT-MS and LC-Q-TOF-MS analyses were used. The results revealed the presence of forty-two constituents comprising glycosinolates, phenylpropanoid glycosides, flavone glycosides, hydroxycinnamic acids, and other compounds. Then, the resultant extracts were subjected to an assessment of the potential cytotoxic effect on human colon adenocarcinoma cells, the effect on the growth of probiotic and intestinal pathogenic strains, as well as their anti-inflammatory activity. It was demonstrated that 60% ethanol extract from the biennial roots (WR2) had the strongest anti-inflammatory, antibacterial, and cytotoxic activities compared to the other samples. Our results suggest that extracts from E. japonicum may be considered as a promising compound for the production of health-promoting supplements.

Biosynthesis, mosquito larvicidal potential, and anticancer activities of gold nanoparticles from Acacia sinuata seed extract

Introduction and Aim: Worldwide, mosquitoes are the main vectors of many deadly diseases like malaria, dengue, chikungunya, etc., Anopheles stephensi mosquito which transmits malaria whereas dengue is transmitted mainly by mosquito Aedes aegypti. Current controlling methods such as chemical or microbial pesticides, repellents, biological control agents against mosquito larvae are not so effective. The leading cause of death worldwide is cancer. Nanotechnology can provide alternative effective methods for malaria, dengue and cancer control, diagnosis and treatment. This study investigated the biosynthesis of gold nanoparticles (AuNPs) from Acacia sinuata seed extract and their mosquito larvicidal potential was tested against Aedes aegypti, Anopheles stephensi larvae. The cytotoxic activity of NPs was also analyzed against human cancer cell lines osteosarcoma (MG-63) and colon adenocarcinoma (Caco-2). Materials and Methods: The biosynthesized NPs were confirmed and characterized by conventional techniques UV- visible spectroscopy, FTIR, XRD, HR-TEM, EDX and SAED. Results: The XRD demonstrated the NPs were face-centred, cubic, and crystalline in nature, EDX study confirmed elemental analysis of gold, SAED illustrated the crystalline nature. The HR-TEM studies revealed NPs shape which were mostly spherical and average size of 5.38nm-8.86nm. Third instar larvae of Aedes aegypti, Anopheles stephensi, were susceptible to the larvicidal effects of AuNPs. The synthesized NPs showed a dose-dependent cytotoxic effect against the Caco-2 and MG-63 cell lines, with IC50 (inhibitory concentrations) of 21.31± 0.15 ug/ml and 86.78± 0.23 ug/ml, respectively. Conclusion: These findings reveal that biosynthesized AuNPs have substantial larvicidal and anticancer properties, suggesting they could be used in mosquito control and cancer treatment.

Kudoa septempunctata Spores Cause Acute Gastroenteric Symptoms in Mouse and Musk Shrew Models as Evidenced In Vitro in Human Colon Cells.

Kudoa septempunctata is a myxosporean parasite that infects the trunk muscles of olive flounder (Paralichthys olivaceus) and has been reported to cause foodborne illnesses in humans. However, the molecular mechanisms underlying K. septempunctata spore toxicity remain largely unknown. In this study, the gastroenteropathy of K. septempunctata was examined in human colon adenocarcinoma cells as well as experimental mice inoculated with spores. We found that K. septempunctata decreased transepithelial resistance and disrupted epithelial tight junctions by deleting ZO-1 in Caco-2 monolayers. Additionally, serotonin (5-HT), an emetic neurotransmitter, was increased in K. septempunctata-inoculated cells. In vivo, K. septempunctata spores induced diarrhea in suckling mice (80% in ddY and 70% in ICR mice), with a minimum provocative dose of 2 × 105 K. septempunctata spores. In house musk shrews, K. septempunctata induced emesis within 1 h and induced serotonin secretion in the intestinal epithelium. In conclusion, K. septempunctata may induce diarrhea and emesis by increasing intestinal permeability and serotonin secretion.

(1→3)-α-d-Glucooligosaccharides Increase the Killing Capacity of NK Cells against Selected Human Colon Cancer Cells.

Despite the progress of medicine, colorectal cancer has occupied one of the highest positions in the rankings of cancer morbidity and mortality for many years. Thus, alternative methods of its treatment are sought. One of the newer therapeutic strategies is immunotherapy based on NK cells (natural killers), which are the body's first line of defense against cancer. The aim of the study was to verify the possibility of using (1→3)-α-d-glucooligosaccharides (GOSs) obtained via acid hydrolysis of (1→3)-α-d-glucan from the fruiting body of Laetiporus sulphureus to improve the anticancer effect of NK-92 cells, with proven clinical utility, against selected human colon adenocarcinoma cell lines LS180 and HT-29. The study revealed that the investigated oligosaccharides significantly enhanced the ability of NK-92 cells to eliminate the examined colon cancer cells, mostly by an increase in their cytotoxic activity. The most significant effect was observed in LS180 and HT-29 cells exposed to a two-times higher quantity of NK cells activated by 500 µg/mL GOS, wherein NK-92 killing properties increased for 20.5% (p < 0.001) and 24.8% (p < 0.001), respectively. The beneficial impact of (1→3)-α-d-glucooligosaccharides on the anticancer properties of NK-92 suggests their use in colon cancer immunotherapy as adjuvants; however, the obtained data require further investigation and confirmation.

Comparison of Phytochemical Composition and Untargeted Metabolomic Analysis of an Extract from Cnidoscolus aconitifolius (Mill.) I. I. Johnst and Porophyllum ruderale (Jacq.) Cass. and Biological Cytotoxic and Antiproliferative Activity In Vitro.

Cnidoscolus aconitifolius (CA) and Porophyllum ruderale (PR) are representative edible plants that are a traditional food source in Mexico. This research aimed to analyze the phytochemical composition and untargeted metabolomics analysis of CA and PR and evaluate their antiproliferative effect in vitro. The phytochemical composition (UPLC-DAD-QToF/MS-ESI) identified up to 38 polyphenols and selected organic acids that were clustered by the untargeted metabolomics in functional activities linked to indolizidines, pyridines, and organic acids. Compared with PR, CA displayed a higher reduction in the metabolic activity of human SW480 colon adenocarcinoma cells (LC50: 10.65 mg/mL), and both extracts increased the total apoptotic cells and arrested cell cycle at G0/G1 phase. PR increased mRNA Apc gene expression, whereas both extracts reduced mRNA Kras expression. Rutin/epigallocatechin gallate displayed the highest affinity to APC and K-RAS proteins in silico. Further research is needed to experiment on other cell lines. Results suggested that CA and PR are polyphenol-rich plant sources exhibiting antiproliferative effects in vitro.

Synthesis and Evaluation of 6‐Amino‐2‐styrylchromones as Anticancer Agents

Abstract2‐Styrylchromones, a C‐2 styrene derivative of chromones, possess a broad spectrum of biological activity. However, 2‐styrylchromones are scarce in nature but not to mention the amino‐substituted styrylchromones. We have synthesized fourteen 6‐amino‐2‐styrylchromones and evaluated their anti‐cancer activity on human caucasian colon adenocarcinoma cells (HT‐29). 6‐Amino‐2‐styrylchromones and related derivatives have never been revealed their pharmacology profiles. Among the novel fourteen compounds, we reported that compound 9 h exhibited its potential with the comparable activity with 5‐flurouracil (5‐FU) as a referenced drug.

First iron(II) organometallic compound acting as ABCB1 inhibitor

Five new iron (II) complexes bearing imidazole-based (Imi-R) ligands with the general formula [Fe(η5-C5H5)(CO)(PPh3)(Imi-R)][CF3SO3] were synthesized and fully characterized by several spectroscopic and analytical techniques. All compounds crystallize in centrosymmetric space groups in a typical “piano stool” distribution. Given the growing importance of finding alternatives to overcome different forms of multidrug resistance, all compounds were tested against cancer cell lines with different ABCB1 efflux pump expression, namely, the doxorubicin-sensitive (Colo205) and doxorubicin-resistant (Colo320) human colon adenocarcinoma cell lines. Compound 3 bearing 1-benzylimidazole was the most active in both cell lines with IC50 values of 1.26 ± 0.11 and 2.21 ± 0.26 μM, respectively, being also slightly selective against the cancer cells (vs. MRC5 normal human embryonic fibroblast cell lines). This compound, together with compound 2 bearing 1H-1,3-benzodiazole, were found to display very potent ABCB1 inhibitory effect. Compound 3 also showed the ability to induce cell apoptosis. Iron cellular accumulation studies by ICP-MS and ICP-OES methods revealed that the compounds’ cytotoxicity is not related to the extent of iron accumulation. Yet, it is worth mentioning that, from the compounds tested, 3 was the only one where iron accumulation was greater in the resistant cell line than in the sensitive one, validating the possible role of ABCB1 inhibition in its mechanism of action.