Search

[Display omitted] • Strong autofluorescence emission can be seen in our Re(I) complexes. • Re(I) complexes build up around cellular membranes and within intercellular connections as they wait to enter, as evidenced by the fluorescence microscopy. • Cytotoxicity is related to the nature of the substituent on the phenyl ring. • DNA fragmentation data were complying to results of MTT and mode of cell death. Four tricarbonyl rhenium(I) complexes featuring quinoline ligands (1 – 4) were examined for their potential cytotoxicity properties against three malignant cell lines and one normal cell line of different origins. The most cytotoxic compound among the synthesized complexes was complex 2 , which was formed when [ReBr(CO) 3 (N∧O)] (N∧O = quinoline-2-carboxaldehyde) (1) and para -amino phenol reacted. Its IC 50 values are in the range of 26.05–30.33 μg/mL. Complex 4 , decorated with benzimidazole moiety, has been demonstrated to be harmless to normal mice splenocytes. The cellular localization of 1 – 4 was investigated using fluorescence microscopy to provide insight into their biotargets, cellular localization, and modes of action. Among the evaluated malignant cell lines, complex 2 exhibited the highest levels of apoptotic and necrotic alterations in the MCF-7 cell line. Re(I) complexes appeared to gather inside intercellular connections and around cellular membranes, as seen in the fluorescence microscopy images. Along the cell membrane, the compounds accumulated as well, anticipating their entry. [ABSTRACT FROM AUTHOR]

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets and the SeNP derivatives were examined for their cytotoxicity towards five cancer cell lines. The inhibitory potencies of the best members against Topo I and Topo II were also assayed besides their DNA intercalation abilities. Compound 7d NPs exhibited the best inhibition against Topo I and Topo II enzymes with IC50 of 0.042 and 1.172 μM, respectively. The ability of compound 7d NPs to arrest the cell cycle and induce apoptosis was investigated. It arrested the cell cycle in the A549 cell at the S phase and prompted apoptosis by 41.02% vs. 23.81% in the control. In silico studies were then performed to study the possible binding interactions between the designed members and the target proteins. A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. Cytotoxicity, Topo I and Topo II inhibitory assays, and DNA intercalation abilities were evaluated. Compound 7d NPs showed the best Topo I and Topo II inhibition. Cell cycle arrest, apoptosis induction, and molecular docking studies were performed. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU) represents the cornerstone for colorectal cancer therapy. However, resistance to its action is a major hindrance. This study aimed to investigate the effectiveness of suppressing the activity of PI3K/Akt/mTOR signaling pathway on the chemosensitivity of colorectal cancer cells to 5-FU, as well as to delineate the possible underlying cellular mechanisms and the expected modulation in the expression of specific ABC drug transporters. HCT116 and Caco-2 cells were incubated with 5-FU, LY294002, or PI-103 individually or in combination. Cell viability was monitored using MTT assay. The expression of a panel of drug transporters was evaluated by RT-PCR. Immunofluorescence staining was applied to evaluate the expression pattern of phospho-AKT, phospho-mTOR, and ABGG2. HPLC evaluated the enhancement in the 5-FU cellular uptake. Cell apoptosis was detected by flow cytometry, and cell morphological changes following treatment were inspected under a fluorescence microscope. Additionally, the migration ability of cells following our suggested treatment combination was examined by wound healing assay. The results reveal a notable enhancement in the cytotoxicity of a low dose of 5-FU when combined with a PI3K inhibitor (LY294002 or PI-103). This enhancement was influenced by the significant reduction in the expression of p-AKT and p-mTOR and was also mediated by a significant suppression in the expression of ABCG2 and ABCC5. Consequently, we detected an increase in the cellular uptake and concentration of 5-FU in cells treated with this combination rather than a single 5-FU treatment. Our Suggested combination treatment also induced cell apoptosis and reduced the migration ability of cells. Our data provide evidence that survival signaling pathways represent distinctive targets for the enhancement of chemotherapeutic sensitivity. The antitumor efficacy of 5-FU is enhanced when combined with a PI3K inhibitor, and this effect was mediated by alterations in the expression of specific drug transporters. • The antitumor potential of 5-FU is hindered by the development of drug resistance and toxicity at high doses. • PI3K/AKT pathway is an effective target for enhancement of chemotherapeutic sensitivity. • A combination of 5-FU and a PI3K inhibitor could enhance the chemosensitivity of colorectal cancer cells. • The cytotoxicity enhancement of 5-Fu is mediated by a reduction in the expression of some drug transporters. [ABSTRACT FROM AUTHOR]

Background The photothermal properties of gold nanoparticles (GNPs) are promising therapeutic modality for cancer. The study objective is to evaluate the therapeutic effect of the prepared PEGylated gold nano-semicubes (PEG-GNSCs) in skin cancer. The synthesized PEG-GNSCs were intermediate between cubic and rod shapes (low aspect ratio- rods). Methods In vitro toxicity was investigated in human skin melanoma Sk-Mel-28 cells, and skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Results The calculated IC 50 in Sk-Mel-28 cells was 3.41 μg/ml of PEG-GNSCs, in presence of laser exposure. Photothermal therapy using laser-stimulated PEG-GNSCs resulted in inhibited volume of skin tumors. Our findings indicated that the inflammatory mediators, nitric oxide and cycloxygenase-2, were inhibited in mice after being treated with low and high doses of PEG-GNSCs, accompanied with laser exposure. However, the tumor necrosis factor -α was markedly elevated, while there was no change in 5-lipoxygenase. The pro-angiogenic factor vascular endothelial growth factor was inhibited, while histone acetylation and apoptosis were induced in tumor-bearing groups, after being treated with laser-stimulated PEG-GNSCs. Conclusion The present study indicated the promising photothermal therapeutic effect of laser-stimulated PEG-GNSCs as an effective modality to inhibit the tumor growth, the angiogenesis and partially the inflammation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cerium substituted HA at different concentrations were prepared and characterized. • The antimicrobial study of prepared samples showed effective antimicrobial action. • The biocompatibility test demonstrated that all prepared samples were nontoxic. • The prepared materials have high potential to employ as drug delivery systems. • Cerium substituted HA can be used as a local treatment of bone cancer. The current study used the precipitation method to prepare pure calcium hydroxyapatite (HA) and cerium-substituted hydroxyapatite (Ce-HA) nanoparticles, where cerium ions were exchanged into the HA structure at different concentrations ranging from 3 to 7 wt%. X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), high resolution transmission electron microscopy (HR-TEM), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) surface area measurements, and zeta potential were used to examine the structural characteristics of the nanoparticles. Additionally, the antibacterial and antifungal effects of the produced materials on Gram-positive, Gram-negative, and fungal bacterial species were studied. Nanoparticles with cerium doping showed effective antibacterial and antifungal properties. All samples were tested for bioactivity in simulated body fluid (SBF), and the formation of an apatite layer on their surfaces was highlighted using SEM in conjunction with energy-dispersive X-rays (EDX).Doxorubicin (DOX) release from Ce-HA nanoparticles and pure HA was tested in phosphate-buffered saline (PBS) for up to 28 days. Both nanoparticles were able to release the drug while still being semi-fully loaded. Similarly, the cytotoxic effect of all produced samples on the MG-63 cell line was evaluated, and all samples showed good cytocompatibility. The cytotoxic effect of doxorubicin-loaded nanoparticles showed promising anticancer activity against bone cancer cells, especially samples with high cerium content. The resulting nanoparticles show excellent promising ability for the delivery of doxorubicin to bone cancer with the capacity for bone regeneration. [ABSTRACT FROM AUTHOR]

• Silencing TNFRSF13B (TACI) led to significant death in breast cancer cell lines. • Silencing inhibited anti-apoptotic/pro-survival markers: TNFR2, Bcl-2, and NF-kB. • Silencing increased Cyclin-D2 and PCNA, but cells were arrested before mitosis. • Silencing led to different cell type-dependent BAFF, BAFF-R, and APRIL expressions. TNFRSF13B, TACI, is a member of the TNF receptor superfamily; it plays a key role in cancer cell proliferation and progression. Influence of silencing of human cytokine receptors on cell viability was screened by Luminescent Cell Viability Assay, after transfection of the siRNA library to find the maximum cell death superhits in both triple-negative MDA-MB-231 and double-positive MCF7 breast cells. The mode of cell death was investigated by dual DNA fluorescence staining. The expression of mRNAs of TACI, BAFF, BAFF-R, and APRIL was explored by qPCR. Immunocytofluorescence analysis was used to evaluate changes in TACI, Bcl-2, TNFR2, cyclin-D2, and PCNA. NF-kB p65, cell cycle, and necrosis/apoptosis (late and early) were analyzed by flow cytometry. TACI is the most potent cytotoxic superhit resulted from high-throughput screening of the siRNA library, in both types of cells. Our findings indicated that silencing receptor TACI in both types of breast cancer cells led to significant cell death, after different intervals from siRNA transfection. Cell death mediators (TNFR2, Bcl-2, and NF-κB) were significantly decreased after TACI silencing. The key factors for cell division (Cyclin-D2 and PCNA) were significantly increased in silenced cells of both types but the cell cycle was arrested before the completion of mitosis. Expression of BAFF, BAFF-R and APRIL mRNA in TACI-silenced cells showed significant upregulation in MDA-MB-231 cells, while only BAFF-R and APRIL showed significant downregulation in MCF7 cells. TACI silencing can be a new and promising therapeutic target for mesenchymal-stem like triple-negative breast cancer subtype. [ABSTRACT FROM AUTHOR]

• Lapatinib induced cytotoxic and genotoxic effects on MDA-MB-231 cell line. • Lapatinib IC 50 value was 32.5 μM after 24 h on MDA-MB-231 cells. • Lapatinib triggered extensive DNA damage as recorded with micronucleus test. • Laptinib reduced the EGFR protein expression and EGFR gene signals. • Lapatinib elevated the apoptotic cell death and as well TP53 gene signals. Lapatinib, one of the tyrosine kinase inhibitors (TKIs), is used to reduce epidermal growth factor family proteins overexpression. This study aims to assess the cytotoxic and genotoxic effects of lapatinib on the triple negative breast cancer cell line "MDA-MB-231". We investigated the cytotoxicity of lapatinib by MTT assay, mode of cell death using apoptosis-necrosis assay, DNA damage using micronucleus test, EGFR protein expression by immunocytochemistry, and assessed its effect on EGFR (7p11.2 locus) and TP53 (17p13 locus) genes using interphase-FISH technique. Lapatinib induced cytotoxicity on MDA-MB-231 cell line by elevating the concentration and its IC 50 value was 32.5 μM after 24 h. Lapatinib increased apoptotic cells and micronuclei in binucleated cells gradually by increasing the concentration for 24 h. The EGFR protein expression was reduced by double fold that expressed in non-treated cells. Lapatinib enhanced deletion of EGFR gene signals highly significantly from the lowest concentration. Alternatively, lapatinib amplified signals of TP53 gene effectively by raising the concentration. In conclusion, lapatinib induced cytotoxic and genotoxic effects on MDA-MB-231 cell line. However, laptinib reduced the EGFR protein expression and EGFR signals, it raised the apoptotic cells and TP53 gene signals, which triggered extensive DNA damage. Therefore, lapatinib is an effective TKI in triple negative breast cancer cells as elucidated by its mode of cell death. [ABSTRACT FROM AUTHOR]

The exceptional antioxidant properties of beetroot (BR) and the cancer antiproliferative effects of chitosan nanoparticles (CS NP) have led to the synthesis of a BR@CS nanocomposite (NC) in this study. The novel BR@CS NC was applied to human epithelial colorectal adenocarcinoma (Caco-2), human epithelial ductal breast carcinoma (T-47D), and human epithelial lung carcinoma (A549) cells. SEM characterization of CS NP revealed a variety of particle shapes ranging from 20 to 58 nm in diameter. UV-VIS analysis confirmed the formation of the BR@CS NC, while FTIR analysis demonstrated strong hydrogen bonds between CS NP and BR. These bonds reduced the positive surface charge of CS NP, as indicated by zeta potential analysis. When applied to cancer cell lines at a concentration of 250 μg/mL, the BR@CS NC successfully eradicated 89 % of A549, 88 % of T-47D, and 83 % of Caco-2 cell lines. The cell death mode exhibited extensive, apoptotic, and massive necrotic changes in all cell lines treated with BR@CS NC. Caspase 3 (CasP3) and P53 levels were elevated in BR@CS NC-treated cells. This study merges BR's antioxidant and anti-inflammatory properties with the antiangiogenic mechanism and inhibition of tumors by CS NP, resulting in a unique and innovative strategy for cancer treatment. • Merging the anticancer assets of CS NP and BR created a novel cancer therapy. • BR@CS NC (250 μg/mL) eradicated 89 % of A549, 88 % of T-47D, and 83 % of Caco-2. • Levels of CasP3 and P53 were promoted in all BR@CS NC-treated cells. • BR@CS NC and CS NPs cells uptake shows selectivity towards mucus cells. • BR@CS NC treated cells showed extensive apoptotic and necrotic changes. [ABSTRACT FROM AUTHOR]

A series of Pd(II) complexes of the general formula [PdX(NNS)] (X = Cl, Br, I, NCS and phenyl-tetrazole-thiolato; NNS = 2-quinolinecarboxyaldehyde-N4-phenylthiosemicarbazone) was tested against four malignant cell lines for their antiproliferative properties and the outcomes were compared to those seen in normal mouse splenocytes. Various auxiliary ligands were substituted in order to investigate the impact of the character of the ligand on the cytotoxicity of this class of Pd(II) complexes. The iodo complex was the most cytotoxic compound towards the Caco-2 cell line in this study. The improved apoptosis and necrosis cell modes were in accordance with the fragmentation results of DNA, which revealed increased fragmentation terminals, especially in isothiocyanate and tetrazole-thiolato complexes. After 24 hours, at half the IC50 of each complex, the complex-treated cells exhibited considerable genotoxicity when compared to the corresponding non-treated control especially in the case of isothiocyanate and tetrazole-thiolato complexes. [ABSTRACT FROM AUTHOR]

Objective: Workers in secondary aluminum production plants are occupationally exposed to polycyclic aromatic hydrocarbons (PAHs). We aimed to monitor the concentrations of PAHs in air and in serum of workers at two secondary aluminum production plants. We also investigated the potential risk of lung cancer development among PAHs exposed workers with emphasis on the role of A1AT mutation and APEX1 gene polymorphisms. Methods: This study included 177 workers from administrative departments and production lines. Blood samples were obtained for estimation of benzo(a)pyrene diol epoxide albumin adduct (BPDE-Alb adduct), anti-Cyclin-B1 marker (CCNB1) and squamous cell carcinoma antigen (SCCAg). Genes' polymorphism for human apurinic/apyrimidinic endonuclease (APEX1) and alpha-1-anti-trypsin (A1AT) gene mutation were detected. Results: There was a significant increase in the level of BPDE-Alb adduct among exposed workers in comparison to non-exposed group. Moreover, 41.67% of exposed workers in El Tebbin had BPDE-Alb adduct level ≥ 15 ng/ml versus 29.6% of workers in Helwan factory. There was a significant increase in tumor markers (SCCAg and CCNB1) among workers whose BPDE-Alb adduct ≥ 15 ng/ml. There was a significant increase in the level of BPDE-Alb adducts in exposed workers carrying homozygous APEX1 genotype Glu/Glu. Furthermore, exposed workers with the Glu/Glu genotype had high tumor markers levels. There was a significant increase in levels of BPDE-Alb adducts in workers carrying A1AT mutant allele. Moreover, workers with mutant A1AT genotype had significantly high tumor markers (SCCAg and CCNB1) levels. Conclusion: Therefore, we conclude that aluminum workers may be at a potential risk of lung cancer development due to PAHs exposure. Although PAHs concentrations in air were within the permissible limits, yet evidence of DNA damage was present as expressed by high BPDE-albumin adduct level in exposed workers. Also, elevation of tumor markers (SCCAg and CCNB1) in exposed workers points to the importance of periodic biological monitoring of such workers to protect them from cancer risk. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) of magnetite (M) and zinc ferrites (Zn 0.5 M and ZnM) with different zinc concentrations were synthesized through a co-precipitation method and coated with chitosan containing ciprofloxacin antibiotic to enhance the cells compatibility to these nanosystems. The prepared magnetic nanoparticles (MNPs), chitosan/MNPs and ciprofloxacin/chitosan/MNPs were characterized using X-ray diffraction (XRD), transmittance electron microscopy (TEM), scanning electron microscopy (SEM) accessorized with energy dispersive X-rays (EDAX), vibrating-sample magnetometer (VSM), Fourier transform infrared (FTIR) and BET surface area measurements. Antibacterial properties of the MNPs were examined against Candida albicans (yeast), Bacillus cereus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria). The drug-loaded NPs were also studied for their efficiency of ciprofloxacin release. The average crystallite size of the fabricated NPs was 10.4 nm (Fe 3 O 4) and 14 nm (ZnFe 2 O 4) for samples M and Zn 0.5 M, respectively. The surface areas of the achieved specimens were recorded to be 145.92 ± 2.32, 102.94 ± 0.39 and 168.71 ± 2.05 m²/g for M, Zn 0.5 M and ZnM, respectively. The saturation magnetization values were determined to be approximately 38.7, 60.6 and 2 emu/g for M, Zn 0.5 M and ZnM, respectively. It was revealed that the bactericidal activity towards the tested strains was highly pronounced for the nanosytems containing ciprofloxacin drug alongside with those substituted with zinc. During a period of 30 days, the total dosage of released ciprofloxacin from CipChM, CipChZnM and CipChZn 0.5 M was 82 %, 90 % and 96 %, respectively. Finally, cells viability and proliferation of different cell lines were found to be increased by the developed nanosystems, especially by those containing zinc and chitosan in the presence of extra MNPs. [Display omitted] • Pure magnetite and Zn substituted nanosystems were successfully prepared using chemical precipitation method. • Chitosan loaded with ciprofloxacin was applied to the MNPs to enhance their biocompatibilities. • Nanosytems containing ciprofloxacin and substituted with zinc demonstrated increased cells viability and proliferation. [ABSTRACT FROM AUTHOR]

In the current study, two series of novel thiazolidin-4-one benzenesulfonamide arylidene hybrids 9a-l and 10a-f were designed, synthesized and tested in vitro for their PPARɣ agonistic activity. The phenethyl thiazolidin-4-one sulphonamide 9l showed the highest PPARɣ activation % by 41.7%. Whereas, the 3-methoxy- and 4-methyl-4-benzyloxy thiazolidin-4-one sulphonamides 9i , and 9k revealed moderate PPARɣ activation % of 31.7, and 32.8%, respectively, in addition, the 3-methoxy-3-benzyloxy thiazolidin-4-one sulphonamide 10d showed PPARɣ activation % of 33.7% compared to pioglitazone. Compounds 9b , 9i , 9k , 9l , and 10d revealed higher selectivity to PPARɣ over the PPARδ, and PPARα isoforms. An immunohistochemical study was performed in HepG-2 cells to confirm the PPARɣ protein expression for the most active compounds. Compounds 9i , 9k , and 10d showed higher PPARɣ expression than that of pioglitazone. Pharmacological studies were also performed to determine the anti-diabetic activity in rats at a dose of 36 mg/kg, and it was revealed that compounds 9i and 10d improved insulin secretion as well as anti-diabetic effects. The 3-methoxy-4-benzyloxy thiazolidin-4-one sulphonamide 9i showed a better anti-diabetic activity than pioglitazone. Moreover, it showed a rise in blood insulin by 4-folds and C-peptide levels by 48.8%, as well as improved insulin sensitivity. Moreover, compound 9i improved diabetic complications as evidenced by decreasing liver serum enzymes, restoration of total protein and kidney functions. Besides, it combated oxidative stress status and exerted anti -hyperlipidemic effect. Compound 9i showed a superior activity by normalizing some parameters and amelioration of pancreatic, hepatic, and renal histopathological alterations caused by STZ-induction of diabetes. Molecular docking studies, molecular dynamic simulations, and protein ligand interaction analysis were also performed for the newly synthesized compounds to investigate their predicted binding pattern and energies in PPARɣ binding site. [Display omitted] • Novel thiazolidin-4-one benzenesulfonamide hybrids 9a-l and 10a-f were designed and synthesized. • The synthesized compounds were tested in vitro for their PPARɣ, PPARα, and PPARδ agonistic activities. • Compounds 9i , 9k , and 10d showed higher PPARɣ expression than that of pioglitazon. • The benzenesulphonamide 9i showed a better in vivo anti-diabetic activity by 40% and improved insulin sensitivity. • Compound 9i showed no pancreatic, hepatic, and renal histopathological alterations. [ABSTRACT FROM AUTHOR]

Fabrication of scaffolds for nerve regeneration is one of the most challenging topics in regenerative medicine at the moment, which is also interlinked with the development of biocompatible substrates for cells growth. This work is targeted towards the development of green biomaterial composite scaffolds for nerve cell culture applications. Hybrid scaffolds of hydroxyethyl cellulose/glycine (HEC/Gly) composite doped with different concentrations of green ruthenium oxide (RuO 2) were synthesized and characterized via a combination of different techniques. X-rays diffraction (XRD) and differential scanning calorimetry (DSC) analyses showed a crystalline nature for all the samples with noticeable decrease in the peak intensity of the fabricated scaffolds as compared to that for pure glycine. Fourier transform infrared spectroscopy (FTIR) tests revealed an increase in the vibrational bands of the synthesized RuO 2 containing scaffolds which are related to the functional groups of the natural plant extract (Aspalathuslinearis) used for RuO 2 nanoparticles (NPs) synthesis. Scanning electron microscopy (SEM) results revealed a 3D porous structure of the scaffolds with variant features attributed to the concentration of RuO 2 NPs in the scaffold. The compressive test results recorded an enhancement in mechanical properties of the fabricated scaffolds (up to 8.55 MPa), proportionally correlated to increasing the RuO 2 NPs concentration in HEC/Gly composite scaffold. Our biocompatibility tests revealed that the composite scaffolds doped with 1 and 2 ml of RuO 2 demonstrated the highest proliferation percentages (152.2 and 135.6%) compared to control. Finally, the SEM analyses confirmed the impressive cells attachments and differentiation onto the scaffold surfaces as evidenced by the presence of many neuron-like cells with apparent cell bodies and possessing few short neurite-like processes. The presence of RuO 2 and glycine was due to their extraordinary biocompatibility due to their cytoprotective and regenerative effects. Therefore, we conclude that these scaffolds are promising for accommodation and growth of neural-like cells. [ABSTRACT FROM AUTHOR]

Developing biomaterial implants for bone regeneration usages has earned great attention during the last two decades. Doping technique is one of the recent approaches that have great promises in the enhancement of biomaterials features. Herein, the features of biphasic TCP/HA were modified by single and co-doping using silver (Ag+) and zirconium (Zr4+) on the expense of calcium utilizing chemical precipitation method. Doping effect on the physicochemical, thermal behaviour, particles charge, morphologies and mechanical properties was determined. Furthermore, dielectric, antibacterial activity, bioactivity and cell death mode (MG63 cell line) were also evaluated. It was confirmed that surface area and total pore volume of the prepared samples were improved upon doping. Negative particle charges, especially for the Zr4+ and the co-doped samples, were confirmed. The co-doped TCP/HA samples possess a strong bactericidal effect against all tested strains compared with the single-doped samples. They also showed a significant effect on the bioactivity properties and the electrical conductivity. The cell mode of death results also supports the importance of transition metal single and co-doping. Implementation of current co-doped biphasic calcium phosphate materials in bone reformation is encouraged due to their proved enhanced features. [ABSTRACT FROM AUTHOR]

Pectin is widely used in food and pharmaceutical industries. However, due to its polysaccharide nature it lacks antimicrobial activity. In the current work, new pectin derivatives with interesting optical and antimicrobial properties were prepared via supramolecular chemistry utilizing Fe- or Cu-terpyridine (Tpy-Fe and Tpy-Cu) motifs. To proof derivatization of pectin, ultraviolet-visible spectroscopy (UV–Vis) and Fourier Transform infrared (FTIR) were used. In addition, the prepared pectin derivatives retained the known emulsification activity of the non-modified sugar beet pectin as seen from the particle size analysis of oil-in-water emulsions. The prepared derivatives showed antibacterial activity toward selected Gram-positive and Gram-negative bacteria. In addition, cytotoxicity test showed that the Tpy-Fe-pectin derivative was non-toxic to cells of human hepatocarcinoma, breast adenocarcinoma MCF7, and colorectal carcinoma cells at concentrations up to 100 μg/ml, while Tpy-Cu-pectin had moderate toxicity toward the aforementioned cells at the same concentration levels. The prepared derivatives could have potential applications in emulsions with antibacterial activity. • New pectin derivatives were prepared using CuII- and FeII-terpyridine complexes. • The terpyridine-pectin derivatives had good emulsification properties for O/W emulsions. • The prepared terpyridine-pectin derivatives showed good antibacterial properties. • Terpyridine-Cu-pectin derivative showed moderate cytotoxicity. • Terpyridine-Fe-pectin derivative showed non-cytotoxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Series of 2-arylbenzimidazole derivatives 12a , b , 13a-d and 14a-l were synthesized. • Compounds 14c and 14g-i were the most potent anticancer activities against cancer cell lines panel (GI 50 values 1.1–30.0 µM). • Compound 14g was found to be a potent RAF kinases inhibitor against BRAF (wt), BRAF (V600E) and CRAF, IC 50 = 0.02, 0.002 and 0.10 µM, respectively. • CRAF homology modeling and molecular docking studies on BRAF, CRAF and VEGFR-2 were also performed for the synthesized compounds. In the current study, series of 2-arylbenzimidazole-thiopyrimidine and -thioquinazolin-4(3 H)-ones conjugates 12a-d , 13a , b and 14a-l have been synthesized. All the synthesized compounds were tested in vitro for their anticancer activities against a panel of cancer cell lines at NCI - US and their growth inhibition (GI) % were determined at 10 µM. Compounds 14c and 14g-i were selected to be screened at the five dose assay and were found to exhibit GI 50 values 1.1–30.0 µM. The benzimidazole-quinazolinone derivative 14c , in particular, showed potent anticancer activity against the tested cancer cell lines (GI 50 of 1.3–4.2 µM). In addition, compounds 12a , b , 13a , 14a-e , 14g , 14i and 14j were selected to be tested against some cancer cell lines using MTT assay and the benzimidazole-quinazolinone 14g was found to have potent anticancer activities against melanoma (Mel-501 and A-375), breast (MCF-7), colon (HCT-116), prostate (PC-3), lung (A-549) and pancreas (Paca-2) cancer cell lines reporting IC 50 values ranging between 0.1 and 6.2 µM. Moreover, the synthesized hybrids were tested in vitro on kinases; BRAF (wt), BRAF (V600E), CRAF and VEGFR-2. The benzimidazole-quinazolinone derivatives 14f , g revealed potent RAF kinases inhibitory activities on BRAF (wt), BRAF (V600E) and CRAF showing IC 50 values 0.002–0.1 µM, whereas, the benzimidazole-quinazolinone derivatives 14i and 14k showed moderate VEGFR-2 inhibitory activity (IC 50 = 20.60 and 6.14 µM, respectively). Moreover, the representative compounds 14g and 14i caused cell cycle arrest of A-375 melanoma cell line at G2/M phase and were found to induce late apoptosis. CRAF in the DFG-out inactive conformation homology modeling was first reported in this study and molecular docking studies on BRAF, CRAF and VEGFR-2 were also performed to investigate the binding modes of the target compounds and their interactions with the key amino acids; BRAF (Glu500, Cys531 and Asp593), CRAF (Glu393, Cys424 and Asp486) and VEGFR-2 (Glu885, Cys919 and Asp1046). [ABSTRACT FROM AUTHOR]